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					                                                       ESSENTIAL                                                                                   DRUGS
  WORLD HEALTH ORGANIZATION                            MON ITOR
                                                                                                                              DOUBLE ISSUE – No 28 & 29 (2000)

  Essential Drugs Monitor                         EDITORIAL
  The Essential Drugs Monitor is produced




                                                  Antimicrobial
  and distributed by the WHO Department
  of Essential Drugs and Medicines Policy
  (EDM). It is published in Chinese, Eng-
  lish, French, Spanish and Russian, and
  has a global readership of some 300,000
  to whom it is free of charge. The Monitor




                                                  resistance:
  carries news of developments in national
  drug policies, therapeutic guidelines, cur-
  rent pharmaceutical issues, educational
  strategies and operational research.
  WHO’s Department of Essential Drugs




                                                  a global threat
  and Medicines Policy seeks to ensure that
  all people – wherever they may be – are
  able to obtain the drugs they need at a price
  that they and their country can afford; that
  these drugs are safe, effective and of good
  quality; and that they are prescribed and
  used rationally.
  All correspondence
  should be addressed to:
                                                              wenty years ago physicians in                     Spread of resistant pneumococcus
                                                    T
  The Editor
  Essential Drugs Monitor                                     industrialised countries believed
  World Health Organization
  CH-1211 Geneva 27, Switzerland
                                                              that infectious diseases were a                        first identified in Spain
                                                              scourge of the past. With indus-
  Fax: +41 22-791-4167
  e-mail: medmail@who.int
                                                              trialisation came improved sani-
                                                  tation, housing and nutrition, as well as the
                                                                                                                                                                                  South
                                                  revolutionary development of disease-                                               Spain                                       Korea
                                                                                                    USA
                                                  fighting antimicrobials. Populations living
 IN THIS ISSUE:                                   in those nations were not only enjoying an      Mexico                                                                          Taiwan, China
                                                  unprecedented decrease in mortality and                                                                                       Hong Kong
Newsdesk                                    2–6   morbidity but a corresponding increase in                                                                               Thailand
                                                  life expectancy. In the developing world –                                                                                         Philippines
Pregnant women in developing
  countries face unacceptable
                                                                                                                                                                            singapore/
                                                  where poverty and ongoing civil distur-                Colombia
  health risks                                                                                                                                                              Malaysia
                                                  bance offset often modest health gains –
New international training course
                                                  people could nevertheless look forward to                         Brazil
  promotes better community drug use
Organizations draw up ethical                     a time when an increased quality of life
  guidelines                                      might one day lead to a relatively disease                                                   South
And much more...                                                                                                    Uruguay
                                                  free future. The tools were there. Confident                                                 Africa
                                                  in the available pharmacopoeia, the major                    Argentina
Antimicrobial Resistance                  7–19
We look at the problem and some                   drug manufacturers turned away from
                                                  intensive antibacterial research and con-                    Chile
 possible solutions to one of the
 world’s greatest health challenges               centrated their energies on seeking cures for
                                                                                                                                   Source: K. Klugmann, South African Institute of Medical Research
                                                  heart disease and other chronic conditions.
Letters to the Editor                        19   Since the l980s significant breakthroughs
                                                  have been largely confined to the develop-      cross all environmental and ethnic boun-          leaving behind only those resistant to the
National Drugs Policy                   20–21
                                                  ment of antiviral agents targeting the          daries. Multi-drug resistant tuberculosis         antimicrobial onslaught. These organisms
Africa’s essential drug programme
   managers discuss future                        ever-widening HIV epidemic.                     (MDR/TB) is no longer confined to any one         can then either pass on their resistance
WHO’s Director-General speaks out                     But tragically, and even before devel-      country or to those co-infected with HIV,         genes to their offspring by replication, or
   for generics                                   oping countries were able to fully benefit      but has appeared in locations as diverse as       to other related bacteria through “conjuga-
Plus Australia’s National Medicines               from medical advances, we face a major          Africa, Asia and Eastern Europe, among            tion” whereby plasmids carrying the genes
   Policy
                                                  risk that diseases considered vanquished        health care workers and in the general popu-      “jump” from one organism to another. This
Access                                  22–27     in industrialised countries, will once again    lation. Penicillin resistant pneumococci are      process is a natural, unstoppable phenom-
Initiatives to create a healthier world           become killers stalking society, bringing an    likewise spreading rapidly, while resistant       enon exacerbated by the abuse, overuse and
NGOs focus on access to drugs                     ever present threat of sudden death and dis-    malaria is on the rise, disabling and killing     misuse of antimicrobials in the treatment
Improving drug supply in Dar es                   ability. The risk that threatens to turn back   millions of children and adults each year.        of human illness and in animal husbandry,
   Salaam
                                                  the clock to a darker age in industrialised         In 1990 almost all cholera isolates in New    aquaculture and agriculture. Disease –
Drug Information                        28–31     countries and to block health progress in       Delhi, India, were sensitive to the cheap,        and therefore resistance – also thrives in
Pakistan’s Drug Helpline                          the developing world is antimicrobial           first-line drugs furazolidone, ampicillin,        conditions of civil unrest, poverty, mass
Increasing workload for Tehran’s Drug             resistance.                                     co-trimoxazole and nalidixic acid. Now,           migration and environmental degradation
  and Poison Information Centre                       As early as half a century ago – just a     formerly effective drugs are largely useless      where large numbers of people are exposed
                                                  few years after penicillin was put on the       in the battle to contain cholera epidemics.       to infectious diseases, with little in the way
Research                                     31
                                                  market – scientists began noticing the              Although most drugs are still active, the     of the most basic health care. Our challenge
Burkina Faso study shows importance
  of qualitative monitoring                       emergence of a penicillin/resistant strain of   lengthening shadow of resistance means            is to slow the rate at which resistance
                                                  Staphylococcus aureus, a common bacte-          that many of them may not be for long. In         develops and spreads.
Meetings, Courses & Netscan             32–33     rium in the human body’s normal bacterial       the case of tuberculosis, the emergence of            This Monitor examines the growing
                                                  flora. Resistant strains of gonorrhoea, dys-    multi-drug resistant bacteria means that          spread of antimicrobial resistance and its
Published Lately                        33–34     entery-causing shigella (a major cause of       medication that once cost US$20 must now          underlying causes. It reports on the actions
                                                  premature death in developing countries)        be replaced with drugs a hundred times            of WHO and others to raise awareness of
Traditional Medicine                         35   and salmonella rapidly followed. From that      more expensive.                                   the issue and to counteract this serious
India’s Biodiversity Bill                         first case of resistant staphylococcus, the         Pathogens develop resisistance to anti-       menace to public health. And it looks at
                                                  problem of antimicrobial resistance has         microbials through a process known as             what you, the reader, whether you are a
World Trade                             35–36
                                                  snowballed to a serious public health con-      natural selection. When a microbial popu-         policy-maker, health care professional,
A health-sensitive approach to
  patent legislation                              cern with economic, social and political        lation is exposed to an antibiotic, more          health advocate or member of the public,
                                                  implications that are global in scope, and      susceptible organisms will succumb,               can do to help tackle the problem. ❏
2                                                                                                                         ESSENTIAL DRUGS MONITOR




    NEWSDESK




First conference on                                                                          A world of difference:
                                                                                             grim statistics on maternal health
consumer adverse                                                                             in developing countries

reaction reporting                                                                            A
                                                                                                      woman living in Africa has a life-
                                                                                                      time risk of dying from compli-
                                                                                                      cations related to pregnancy 200
                                                                                                                                         and reproductive ill-health because they
                                                                                                                                         also suffer discrimination in access to
                                                                                                                                         basic needs, health services and the
                                                                                                      times greater than a woman liv-    exercise of human rights.”
             ➢ DAVID FINER*                        With so many excellent reasons for        ing in a wealthy industrialised country,        Another Bulletin article reviews data
                                                                                             according to research findings reviewed     suggesting that making abortion safer
                                              direct consumer reporting, why, one
        he First International Conference                                                    in the WHO Bulletin*.                       could save the lives of many thousands
                                              might ask, is it not already established?

    T
                                                                                                 WHO data show that of the more than     of women a year. ❏
        on Consumer Reports on Me-            It is because in most countries, consumer      500,000 maternal deaths every year, over
        dicines was held in Sigtuna,          reports are simply not eligible for inclu-     99% are in developing countries and less
        Sweden, from 29 September–            sion in the existing physician-based                                                       * Bulletin of the World Health Organization,
                                                                                             than 1% in the industrialised world. The    May 2000 (available on the Web at: http://
1 October 2000, with some 70 partici-         systems, and because consumers lack            main causes of these deaths are unsafe      www.who.int/bulletin/). For subscription
pants from 35 countries. The Conference       power and knowledge.                           abortion, haemorrhage, infections, high     details contact: World Health Organization,
sought to call attention to the experiences        The Conference recommended that,          blood pressure and obstructed labour. A     Marketing and Dissemination, CH 1211
of consumers as a crucial, untapped force     prior to wide-scale implementation, con-       quarter to a third of all deaths of women   Geneva 27, Switzerland.
in pharmacovigilance, beneficial for drug     sumer reporting on medicines system/s          of reproductive age are
safety, but also in terms of consumer         should be piloted in regions or with           the result of complica-
empowerment in its own right.                 patient groups, and handled by an inde-        tions of pregnancy or
    Direct consumer reporting of adverse                                                     childbirth.
                                              pendent body at arm’s length from
drug events is indeed credible but also                                                          “The poor fare far
                                              government and industry. In aggregated
controversial in some camps. Yet it is                                                       worse than the rest of so-
                                              form, reports should be made available         ciety on all reproductive
the only system based on the end-users        to all interested parties, including the
themselves.                                                                                  health outcome indica-
                                              mass media. The data would also be             tors. But poverty is not
    The Conference was organized by the       related to the current data from the 59        an insurmountable bar-
Swedish organization KILEN (Consumer
                                              national physician-based schemes in the        rier to health when there




                                                                                                                                                                                           Photo: WHO/PAHO/A. Waak
Institute for Medicines and Health) in                                                       is a high level commit-
                                              Uppsala Monitoring Centre (a WHO Col-
cooperation with the Dag Hammarskjöld                                                        ment to investing in
                                              laborating Centre for International Drug
Foundation, Health Action International,                                                     health,” a Bulletin article
                                              Monitoring). Appropriate arrangements
People’s Health Assembly 2000, the                                                           states. “Gender-based
                                              should be made to enable hospitalised
Uppsala Monitoring Centre, the Swedish                                                       discrimination is an
                                              patients as well as participants in clinical
Consumers’ Association, and the Sigtuna                                                      important determinant
                                              drug trials to file reports.
Foundation. Participants included experts                                                    of poor reproductive Hopefully a trouble-free pregnancy for this woman in Haiti. But
from the medical and pharmaceutical                                                          health. Women suffer the women in the developing world have an unacceptably high risk
professions, drug regulatory authorities,     Expert analysis needed                         major burden of sexual of dying from pregnancy-related complications
the consumer movement and WHO.                    The principle of the subject’s freedom
    Presentations of existing consumer        to report should be laid down in Guide-
reporting systems/initiatives were made       lines for Good Clinical Practice accepted

                                                                                             Doctors revise ethical
by representatives from Australia, the        by the European Commission and in clini-
Netherlands, Sweden, Switzerland and          cal trial protocols, subject to approval by
the UK.
    A consensus report from the Con-
ference states that general reasons for
                                              ethics committees and analogous bodies.
                                              Confidentiality agreements concluded
                                              between an industrial sponsor and a clini-
                                                                                             guidelines on medical research
considering consumer reports on medi-
                                              cal investigator should never be allowed                he World Medical Association         Strengthening

                                                                                               T
cines relate to the need to promote
                                              to impede reporting of adverse effects by               General Assembly has sent a          participants’ rights
principles of equity, therapeutic advances,
                                              participants. Provided there is proper                  strong signal to all involved in
accountability and responsiveness. Also,                                                                                                       The Declaration specifies that doctors
                                              feedback and careful expert analysis of                 medical research that rich
existing physician-based systems have                                                                                                      participating in research have an obli-
                                              reports, it will not necessarily be more       populations should not exploit poor
serious deficiencies, which might to some                                                    populations by testing on them new treat-     gation to declare any financial or other
                                              difficult to eliminate mischievous, mis-                                                     potential conflict of interest. Research is
extent be compensated for by the estab-                                                      ments from which they will never benefit.
                                              leading or ambiguous reports than has                                                        justified only if the populations to be stud-
lishment of consumer reporting. Foremost                                                     The Assembly held in Edinburgh, Scot-
                                              been the case in professional-based                                                          ied stand to benefit. The Declaration
among these limitations are the small pro-                                                   land, in October 2000, approved a revised
                                              systems.                                                                                     states that every patient entered into a
portion of practising physicians (often                                                      Declaration of Helsinki. Initially drawn
less than 5%) who contribute data. Input          A system of consumer reporting on                                                        study should have access to the best treat-
                                                                                             up in 1964, the Declaration has since be-
from existing systems relates primarily to    medicines might be supported from pub-                                                       ment identified by that study once it is
                                                                                             come the most widely accepted guidance
new drugs, despite the fact that new prob-    lic funds, drug licensing fees or research     worldwide on medical research involv-         completed. Furthermore, testing of any
lems can emerge with older drugs even         organizations, including the European          ing human participants. Commenting on         new treatment should be done against the
after decades of use.                         Union. Its value will depend to some part      the changes, Dr Anders Milton, chairman       best current method, where that exists,
                                              on enlisting support from existing sys-        of the Association, said: “Research should    and not against a placebo. This would
                                              tems, allaying unjustified concerns and        not be carried out in countries in devel-     mean that people in developing countries
Consumers give more                           countering possible misunderstandings.         opment just because it is cheaper and the     would at least get access to the best cur-
complete picture                                  Delegates warned that while develop-       laws are more lax. The same ethical rules     rent treatment if they agree to take part in
    Delegates heard that benefits of con-     ing consumer empowerment, one must             should apply wherever research is being       research into new treatments.
                                              also seek to counter potentially harmful       conducted”.                                       The revised Declaration of Helsinki
sumer reporting of adverse drug effects
                                              influences, such as current efforts to ex-         The new Declaration emphasises in         will be distributed to WHO, national
include an earlier accumulation of signals,
                                              tend Direct-to-Consumer-Advertising of         much clearer terms than ever before the       bioethics commissions, patients’ repre-
covering a wider spectrum of organ sys-
                                              prescription drugs from New Zealand and        duty that doctors owe to participants         sentatives groups and other relevant
tems and adverse events. Consumers                                                           in medical research. It says that freely
                                              the USA to the rest of the world. ❏                                                          stakeholders. The full text is on the
provide more informative, vivid and com-                                                     given informed consent, preferably in         World Medical Association’s Web site:
plete accounts of unwanted experiences                                                       writing, should be obtained from all
                                              * David Finer is a medical writer and was                                                    www.wma.net ❏
and situations, about which physicians are                                                   participants. People who cannot give
                                              Chairperson of the Conference.
not informed and so cannot report, such                                                      informed consent should be included
as self-treatment with over-the-counter       Further Conference information can be found    in research only under exceptional
drugs or herbals.                             on the Web at: www.kilen.org                   conditions.                                   Source: BMJ 2000;321:913


                                                                                                                                                    Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                                              3




  NEWSDESK




New course targets better                                                                                                                                                                                 WHO’s Emergency
                                                                                                                                                                                                          Library Kits
community drug use                                                                                                                                                                                                ibrary Kits containing essential

         t a time when the majority of         countries, valued the help                                                                                                                                   L     documents related to public
                                                                                                                                                                                                                  health in emergencies are now

 A       medicines are purchased directly
         by consumers without prescrip-
         tion, community education is
                                               given to identify clear objec-
                                               tives, based on realistic
                                               expectations of impact on
                                                                                                                                                                                                                  available from WHO. Intended
                                                                                                                                                                                                          to provide technical guidance to field-
                                                                                                                                                                                                          operating agencies, the Kit includes 120
vital, and a new course is setting out to      future work.                                                                                                                                               documents – guidelines and reference




                                                                                                                                                         Photo: S. Sanders, Mahidol University, Bangkok
meet the needs of those with a critical role       The skills and experi-                                                                                                                                 manuals produced by WHO, other UN
to play in this much neglected area. Just      ences of everyone on this                                                                                                                                  organizations and external publishers.
how neglected was shown by a WHO glo-          highly participatory course                                                                                                                                The contents will be updated regularly.
bal survey on public education in rational     proved a major resource.                                                                                                                                       Packed in a metal trunk that converts
drug use1, which revealed a shortage of        Teaching methods were                                                                                                                                      into a bookcase, the Emergency Library
expertise, support and funds for this type     group activities, field work,                                                                                                                              Kit costs approximately US$1,320, plus
of work, in spite of its public health and     presentations and discus-                                                                                                                                  transport charges. ❏
economic benefits.                             sions. Participants spent the
                                                                                                                                            For further information contact: World Health
    Developed by WHO’s Department of           final two days preparing a
                                                                                                                                            Organization, Department of Emergency and
Essential Drugs and Medicines Policy           detailed plan of action to Creating a message that counts – participants working on a        Humanitarian Action, 1211 Geneva 27,
and the University of Amsterdam, in col-       tackle an important commu- poster during the course                                          Switzerland.
laboration with experts world wide, the        nity drug use problem in
course, Promoting Rational Drug Use in         their home country. They also took home
the Community, was held for the first time     a set of session materials and a small core
in October 2000 in Bangkok. Enthusias-
tic participants learned how to effectively
                                               communications library. But from their
                                               comments it was evident that course                        Welcome new HIV/AIDS
                                                                                                          resource for francophone Africa
identify and prioritise community drug         members were leaving Thailand with
use problems; choose and develop               much more. As one participant put it, “I
appropriate intervention strategies and        realise that in my professional life I have
communication channels; pretest materi-        only been looking at half of the picture...”.          new HIV/AIDS information network for Central and West Africa has been

                                                                                                           A
als; evaluate impact; and fundraise and        Another said the course would “help me                 launched – the first network of this type in French. Known as SAFCO (SIDA
network for support and sustainability.        use scarce resources to implement the                  en Afrique du Centre et de l’Ouest), it will encourage discussion and the
    Anyone who came looking for “quick         most appropriate/feasible and needed in-               electronic exchange of information on HIV/AIDS-related issues. The service
fixes” would have been disappointed.           terventions.” And for a third it was “a       is particularly welcome because there is a scarcity of such information and technical
Participants learned that interventions        great experience, well planned and well       material in French in Africa, the continent hardest hit by the virus.
must take into account the social and eco-     organized”.                                       As well as information exchange, SAFCO aims to: strengthen advocacy efforts;
nomic context in which health- and                 After such initial success the course     improve information about current projects; promote prevention measures; reinforce
medicine-seeking behaviour take place,         is set to become a regular event, with the    access to care and treatment; disseminate the results of international conferences and
and be developed with community input.         next one being held in Entebbe, Uganda,       support their implementation.
The course emphasises that change is           from 11–24 November 2001. ❏                       SAFCO, with over 700 members, is a UNAIDS supported initiative. One of its
usually incremental. So programme                                                                         main strengths is that it is a public cross-sectoral and inter-community information
objectives may start with awareness train-     Reference                                                  forum. It has input from both the “grassroots” – concerned individuals, government
ing, move on to knowledge acquisition,                                                                    representatives, NGOs, educators, investigators, practitioners and others – and from
                                                   WHO. Public education in rational drug use: a global
and then finally on to behavioural change.         survey. EDM Research Series No.24. Geneva: World       national and international institutions. ❏
    Twenty-five participants, from 14              Health Organization; 1997. WHO/DAP/97.5.

                                                                                                          Joining the SAFCO network is free of charge, just send a message to: safco@hivnet.ch

           Next Promoting Rational Drug Use
               in the Community Course                                                                    WHO list of                                                                                     APUA’s small
  If you would like to know more about the course in Entebbe, Uganda, from 11–24
  November 2001, please complete and return this form. Alternatively, further details
  and an application form can be printed out directly from the EDM web-page at:
                                                                                                          comparator                                                                                      grants programme
  http://www.who.int/medicines/organization/par/secondcourse.html. Course fees
  are US$2,950, which covers tuition, course materials and accommodation. The
                                                                                                          products                                                                                                he Alliance for Prudent Use of
  deadline for receipt of applications is 1 October 2001.
                                                                                                                  ultisource (generic) drugs need to
                                                                                                                                                                                                            T     Antibiotics (APUA) has initiated
                                                                                                                                                                                                                  a small grants programme, which
  Name

  Occupation
                                                                                                           M      meet the same quality, safety and
                                                                                                                  efficacy standards as the original
                                                                                                                  brand name or innovator product.
                                                                                                                                                                                                                  provides chapters with seed
                                                                                                                                                                                                          money of US$1,500 for projects designed
                                                                                                                                                                                                          to curb antibiotic resistance and to
  Full postal address                                                                                     WHO has now published a list of globally                                                        promote the rational use of these drugs.
                                                                                                          recognised comparator products, to help                                                             APUA’s national chapters form a glo-
                                                                                                          regulators identify the product against                                                         bal network of health care practitioners
                                                                                                          which bioequivalence and interchange-                                                           and scientific groups working to control
                                                                                                          ability of generic versions can be                                                              antimicrobial resistance. They provide
  Tel                                          Fax
                                                                                                          assessed.                                                                                       information and tailor the Alliance’s
                                                                                                              The list includes 147 drugs from the                                                        message to local customs and medical
  E-mail                                                                                                  WHO Model List for which a compara-                                                             practices, and the small grants programme
                                                                                                          tor product has already been identified.                                                        is intended to encourage these efforts.
  Please return to the address below:                                                                     It names the manufacturer who is the in-                                                        Projects submitted for grants are eva-
                                           University of Amsterdam                                        novator, and the national market where                                                          luated according to their objectives,
                                           Faculty of Social and Behavioural Sciences                     that manufacturer considers that the prod-                                                      collaborative components and manage-
                                           Attn. Dr Ria Reis                                              uct meets the best safety, quality, efficacy                                                    ment plans. To date grants are helping to
                                           Oudezijds Achterburgwal 185                                    and labelling standards. A second list                                                          support research and education in seven
                                           1012 DK Amsterdam                                              gives the remaining essential drugs for                                                         developing and transitional countries. ❏
                                           The Netherlands                                                which a comparator product has yet to be
                                           Tel: +31 20 525 4779                                           selected. ❏                                                                                     For further information contact: The Alliance
                                           Fax: +31 20 525 3010                                                                                                                                           for Prudent Use of Antibiotics, P.O. Box 1372,
                                           E-mail: prduc@pscw.uva.nl                                      The information is available in WHO Drug                                                        Boston MA 021171372, USA. E-mail:
                                                                                                          Information Volume 13, No.3, 1999.                                                              ccogli01@tufts.edu


Issue No. 28 & 29, 2000
                                        4                                                                                                                               ESSENTIAL DRUGS MONITOR




                                            NEWSDESK




                                        Leading organizations’
                                        new guidelines on ethics
                                               t a time of increased focus on             addresses some of these ethical chal-           reflecting a number of issues, including:         The Code applies to management

                                         A     ethical issues in the pharmaceu-
                                               tical sector, UNAIDS and the
                                               European Medicines Evaluation
                                                                                          lenges, took over two years to draw up. It
                                                                                          was based on a series of consultations or-
                                                                                          ganized by UNAIDS and which involved
                                                                                                                                          ➤ international ethical responsibility to
                                                                                                                                            support vaccine trials;
                                                                                                                                          ➤ the obligation to provide an effective
                                                                                                                                                                                        board, scientific committee and working
                                                                                                                                                                                        party members, European experts listed
                                                                                                                                                                                        by the Agency, all Agency staff and
                                        Agency are among many organizations               representatives from 33 countries. The                                                        by analogy all visiting staff. Three cat-
                                                                                                                                            vaccine to populations where trials are
                                        producing their own guidelines.                   meetings took place in Brazil, Thailand                                                       egories of interest are listed: financial
                                                                                                                                            conducted and to other populations in
                                                                                          and Uganda (countries that are participat-                                                    interests, work carried out for the phar-
                                                                                                                                            need;
                                        UNAIDS and vaccine                                ing in HIV vaccine trials) as well as in                                                      maceutical industry in the previous five
                                        research                                          Geneva and Washington. They involved            ➤ the need to strengthen ethical review       years, and other links, such as grants for
                                                                                          lawyers, activists, NGOs, people living           capacity in developing countries;           study or research, or fellowships endowed
                                            In the case of the Joint United Nations
                                        Programme on HIV/AIDS (UNAIDS)                    with HIV/AIDS, social scientists, ethi-         ➤ the importance of social and behav-         by industry in the previous five years.
                                        the ethical guidelines cover HIV vaccine          cists, epidemiologists, health policy             ioural aspects of testing, and future use       Anyone with direct interests in the
                                        research for those giving trial AIDS              specialists, and agencies and institutions        of an HIV vaccine.                          pharmaceutical industry has to end them
                                        vaccines. It is widely thought that devel-        involved in vaccine development.                                                              to remain with the Agency. If there are
                                        oping such a vaccine offers the best hope              There was consensus on most, but not       Collective responsibility                     indirect interests they must be neutralised,
                                        of controlling the AIDS epidemic, espe-           all, issues. The most contentious area was          The guidelines identify responsibili-     for example by preventing someone from
                                        cially in developing countries. But experts       the level of treatment that should be of-       ties for the “sponsors” of vaccine trials.    taking part in certain tasks.
                                        say it will be a lengthy and complex proc-        fered to participants in vaccine trials who     In modern vaccine development pro-                In general staff have to discourage
                                        ess, because of the scientific and ethical        become infected with HIV, not through           grammes, sponsors are not usually a           gifts of anything more than token value
                                        challenges involved in clinical trials            the trials (vaccines cannot cause HIV in-       single pharmaceutical company. Instead,       which can be shared openly with col-
                                        among human volunteers.                           fection) but through eventual behavioural       there tend to be multiple sponsors, with      leagues. Any gifts of a personal nature
                                            The guidance document, which                  exposure. According to the UNAIDS               one or more corporations, one or more         must be returned, and staff must not use
                                                                                                         document, “Care and treat-       national governments, and one or more         items with pharmaceutical company
                                                                                                         ment should be provided,         international agencies.                       logos at work.
                                                                                                         with the ideal being to              The guidelines highlight the impor-           The Code states that invitations to pre-
                                                                                                         provide the best proven          tance of involving communities early in       dominantly leisure events cannot be
                                                                                                         therapy, and the minimum         the design, development, implementation       accepted, and at meetings or on missions
                                                                                                         to provide the highest level     and distribution of results of HIV vaccine    staff should normally pay for their own
Photo: WHO/Institut Pasteur/C. Dauget




                                                                                                         of care attainable in the host   research. They are designed as a frame-       meals. Invitations from individual phar-
                                                                                                         country” under the circum-       work to enable communities to decide          maceutical companies, suppliers, etc.
                                                                                                         stances in which the trial is    what is appropriate for them.                 should not be accepted. In addition no
                                                                                                         conducted.                                                                     payment may be accepted for speeches,
                                                                                                             With resources in indus-                                                   lectures or publications directly related to
                                                                                                                                          Agency acts to ensure
                                                                                                         trialised and developing                                                       Agency activities. Permission to speak at
                                                                                                                                          integrity, independence,
                                                                                                         countries so different, how-                                                   conferences will be refused “if network-
                                                                                                         ever, not every country can      transparency                                  ing or gaining influence must be assumed
                                                                                                         expect to provide the same           The European Medicines Evaluation         to be the major objective of the organ-
                                        The AIDS virus. Development of a vaccine is considered to be
                                        the best hope of controlling the AIDS epidemic. Guidelines
                                                                                                         level of care.                   Agency is to have a code of conduct giv-      izer”. Invitations from congresses or
                                        are now in place to address the complex ethical issues               The document contains        ing specific guidance on conflicts of         meetings organized by pharmaceutical
                                        involved in testing such a vaccine                               18 “guidance points”             interest, gifts and confidentiality.          companies are unacceptable. ❏




                                        Africa’s strategy on                                                                                                                            Electronic
                                                                                                                                                                                        HAI-Lights

                                        traditional medicine                                                                                                                            H
                                                                                                                                                                                                  AI-Lights has become the first
                                                                                                                                                                                                  HAI-Europe publication de-
                                                                                                                                                                                                  signed to be read and used elec-
                                                                                                                                                                                                  tronically. All of the information
                                                 he Strategy for Traditional Medi-       countries. Much discussion focused               economic importance this could have for       included in the newsletter’s August 2000

                                            T    cine for the African Region
                                                 (2000–2001) is being developed
                                                 by the WHO Regional Office for
                                                                                         on ensuring the protection of the intel-
                                                                                         lectual property rights of indigenous
                                                                                         knowledge in traditional medicine, and
                                                                                                                                          Africans.
                                                                                                                                              As a follow-up to the December con-
                                                                                                                                          sultative meeting, WHO’s Regional
                                                                                                                                                                                        double issue appears in easy to find links
                                                                                                                                                                                        shown on the cover page. HAI-Europe
                                                                                                                                                                                        has been working towards a Web-based
                                        Africa. Its aim is to assist Member States       the cultivation and conservation of native       Office for Africa organized the African       version of the regional newsletter for
                                        to integrate traditional medicine into           medicinal plants. Delegates asked WHO            Forum on the role of traditional medi-        some time, due to members’ demand for
                                        health systems and services, and to              to provide technical and financial support       cine in health systems, in Harare in          faster information and more accessible
                                        promote appropriate and rational use.            for developing traditional medicinal prod-       February 2000. Over 100 participants          material.
                                        In December 1999, WHO held a consul-             ucts to combat priority diseases, such as        from throughout the region held wide              It is planned to link the newsletter’s
                                        tative meeting on the Strategy, which            malaria, hypertension, diabetes and HIV/         ranging discussions, reviewed current and     content to a Web site search function so
                                        brought together 23 experts from 15 coun-        AIDS-related conditions.                         needed research on these medicines,           that articles on various issues can be
                                        tries for three days of intensive debate in          Closing the meeting the WHO Re-              and identified local production issues.       retrieved quickly and easily.
                                        Harare, Zimbabwe.                                gional Director for Africa, Dr Ebrahim           Recommendations from the meeting                  Access the August issue of HAI-Lights
                                        Combatting priority diseases                     Samba, said he wanted to see the contin-         included: ensuring adequate legal and         at: http://www.haiweb.org/pubs/hailights/
                                           Participants recommended that action          ued use of African herbal plants and             regulatory frameworks to promote tra-         aug2000/
                                        plans be developed to implement the              traditional medicines to treat diseases. He      ditional medicines; establishing or               The entire newsletter is also available
                                        Strategy at regional and national levels,        hoped that such traditional medicinal            strengthening traditional medicine prac-      in a downloadable text format. You can
                                        so that by 2020 traditional medicine             products would eventually be exported,           titioners’ associations; and increasing       choose Word for either PC or Mac to read
                                        will be an integrated component of the           after clinical trials have proved their effi-    collaboration among healers, scientists       or print out the issue’s complete contents
                                        minimum health care package in African           cacy and safety. Dr Samba stressed the           and doctors. ❏                                or a specific section. ❏

                                                                                                                                                                                                 Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                                          5




                         NEWSDESK




                       French set to curb                                                                                              A World Health Report
                       drug spending                                                                                                   with a difference
                                                                                                                                                he World Health Report 2000 –        system to carry out four main functions:


                         T
                                he French Government has
                                warned that the rate of growth of
                                pharmaceutical spending is still
                                                                                            She singled out “unjustifiable pre-
                                                                                        scribing”, saying that some products were
                                                                                        quickly capturing a sizeable share of the
                                                                                                                                        T       Health Systems: Improving
                                                                                                                                                Performance1 is an expert analy-
                                                                                                                                                sis of the increasingly important
                                                                                                                                                                                     service provision, resource generation,
                                                                                                                                                                                     financing and stewardship. Chapters
                                                                                                                                                                                     devoted to each function offer new con-
                                far too high, and that it is decid-                     market more because of what she termed         influence of health systems in people’s       ceptual insights and practical advice on
                       ing which products will have price or                            “aggressive commercial policies towards        daily lives. In recent decades, health sys-   how to assess performance and achieve
                       reimbursement cuts, or be removed from                           doctors than because they are advances         tems have contributed enor-                              improvements with available
                       the list of reimbursable products.                               in public health”. “Information arrives in     mously to better health for                              resources.
                           Speaking at a press conference in May                        doctors’ surgeries from pharmaceutical         most of the global population.                              The analysis revealed a
                       2000, Labour and Solidarity Minister,                            companies and only from them” she con-         But they have the potential to                           number of problems common
                       Martine Aubry, said that health care                             tinued. “ I am not criticising the industry.   achieve further improvements,                            to many countries. Among
                       expenditure was still rising strongly, par-                      It does its job, which is to sell and sell     especially for the poor. As Dr                           them are that:
                       ticularly in the pharmaceutical sector,                          even more. But she said that she did not       Brundtland, WHO’s Director-                              ➤ many health ministries
                       which increased by 6.3% in 1999. While                           want doctors to be “left alone to face the     General, comments in her                                    focus on the public sector
                       projections for 2000 are for a cut of 0.7%                       industry”. The Government intends to           introduction to the Report,                                 and often disregard the
                       this is far higher than the target set by                        supply doctors with independent infor-         “The poor are treated with less                             frequently much larger
                       Government of 2%. Addressing the                                 mation on the correct use of medicines.        respect, given less choice of                               private sector health care;
                       Social Security Accounts Commission                              While encouraged by increasing generic         service providers and offered                            ➤ in many countries, some if
                       shortly before her press conference, Ms                          substitution, Ms Aubry said that she           lower-quality amenities. In trying to buy        not most physicians work simultane-
                       Aubry said that it was “absolutely neces-                        wanted to see more generic products on         health from their own pockets, they pay          ously for the public sector and in
                       sary” to bring pharmaceutical expenditure                        the market soon.                               and become poorer.”                              private practice. This means that the
                       into line with Government targets.                                   The French pharmaceutical industry             To date very little has been done to         public sector ends up subsidising
                                                                                                  association, SNIP, has criticised    unravel the complex factors that explain         unofficial private practice;
                                                                                                  the Government’s target of a         good or bad performance by individual         ➤ many governments fail to prevent a
                                                                                                  2% increase in pharmaceutical        health systems. Given equal resources,           “black market” in health, where wide-
                                                                                                  spending in 2000. The Govern-        why do some succeed where others fail?           spread corruption, bribery, “moon-
                                                                                                  ment cost-containment ini-           Is performance simply driven by the laws         lighting” and other illegal practices
                                                                                                  tiatives (prescribing guidelines,    of supply and demand, or does another            flourish. The black markets, which
                                                                                                  computerization of doctors’ sur-     logic apply? Why is dissatisfaction with         themselves are caused by mal-
                                                                                                  geries, the encouragement of         services so widespread, even in wealthy          functioning health systems, and
                                                                                                                                       countries offering the latest interven-          health workers’ low incomes, further
Photo: WHO/E. Schwab




                                                                                                  generics and reimbursement
                                                                                                  review) were necessary, SNIP         tions? If systems need improvement, what         undermine those systems;
                                                                                                  stated, but had failed to bring      tools exist to measure performance and        ➤ many health ministries fail to enforce
                                                                                                  spending into line with the 2%       outcomes?                                        regulations that they themselves have
                                                                                                  limit. ❏                                 These are some of the questions that         created or are supposed to implement
                                                                                                                                       the Report addresses, as it presents the         in the public interest.
                       An elderly patient in France, where the Government is                      Source: Scrip, No.2543, 26 May       results of the first ever analysis of the
                       acting to reduce rising pharmaceutical expenditure                         2000.
                                                                                                                                                                                         The Report aims to stimulate debate
                                                                                                                                       world’s health systems. It provides an        about better ways of measuring health
                                                                                                                                       index of performance based on three           system performance and overcoming
                                                                                                                                       fundamental goals: improving the level        such problems. By shedding new light on
                                                                                                                                       and distribution of health, enhancing the     what makes systems behave in certain
                                                                                                                                       responsiveness of the system to the le-
                       Indian training course highlights                                                                               gitimate expectations of the population,
                                                                                                                                       and assuring fair financial contributions.
                                                                                                                                                                                     ways, WHO also hopes to help policy-
                                                                                                                                                                                     makers understand the many complex

                       pharmacists’ evolving role                                                                                          As the Report argues, good perform-
                                                                                                                                       ance depends critically on the delivery of
                                                                                                                                                                                     issues involved, weigh their options and
                                                                                                                                                                                     make wise choices. ❏
                                                                                                                                       high-quality services. But health sys-        Reference
                               group of community and hospital pharmacists and pharmacy students from

                        A
                                                                                                                                       tems must also protect citizens from the      1.   WHO. The world health report 2000 – health systems:
                               the Bengal area benefited from a break in routine when in September 1999                                financial risks of illness and meet their
                                                                                                                                                                                          improving performance. Geneva: World Health
                                                                                                                                                                                          Organization; 2000. Available from: Marketing and Dis-
                               they spent two days looking at broader issues affecting their profession. Twenty-                       expectations with dignified care. The pub-         semination, World Health Organization, 1211 Geneva 27,
                               six participants held wide-ranging discussions on subjects including their                              lication shows how the achievement of
                                                                                                                                                                                          Switzerland. Price: Sw.fr.15/US$13.50, and in develop-
                                                                                                                                                                                          ing countries Sw.fr.10.50. The full report is available on
                       changing role, the structure of the country’s pharmaceutical industry and the                                   these goals depends on the ability of each         the Web at: http://www.who.int/home/reports.html
                       patent situation. Run jointly by the Community Development Medicinal Unit, Cal-
                       cutta, and the Indian Pharmaceutical Association, Bengal Branch, the training course,
                       Good Community Pharmacy Practice, was so successful that it is planned to repeat it
                       every year.

                       Upgrading knowledge and skills                                                                                  Celebrating the Chinese version of
                           In the varied programme, a session on formulations marketed in India although                               the Monitor
                       banned by the Government generated animated debate. So too did the topic of clinical
                       waste management – an area new to many of the participants. The second day began
                                                                                                                                               he Essential Drugs Division of

                                                                                                                                         T
                       with a discussion on how best to respond to symptoms of common ailments, followed
                                                                                                                                               China’s State Drug Adminis-
                       by tips on improving drug dispensing, and medical stores management.
                                                                                                                                               tration has seen its hard work
                           Although maybe not of immediate relevance to the job description of most
                                                                                                                                               rewarded as the first two issues
                       participants, two sessions provided plenty of food for thought. One was on the
                                                                                                                                       of the Monitor in Chinese have rolled off
                       scientific principles of pharmaceutical in-
                                                                                                                                       the printing presses, to an enthusiastic
                       ventory management. The other covered
                                                                                                                                       reception.
                       the structure of the pharmaceutical indus-
                                                                                                                                           Ten thousand copies of each issue
                       try in India, recent changes in national
                                                                                                                                       have been printed and distributed, free
                       drug policy and the Indian patents
                                                                                                                                       of charge, to Government departments,
                       scenario. ❏
                                                                      Photo: CDMU/IPA




                                                                                                                                       medical institutes and experts in the
                                                                                                                                       pharmaceutical sector. While these first
                       For further information contact: Community
                       Development Medicinal Unit, 47/1B Garcha
                                                                                                                                       issues contain a selection of key articles
                       Road, Calcutta-700 019, West Bengal,                                                                            from recent editions, future copies will
                       India, or see: http://education.vsnl.com/                        Participants engrossed by a demonstration of   reproduce the text of the most recent
                       cdmudocu/CDMUHome.htm                                            special dosage forms                           Monitor. ❏

                       Issue No. 28 & 29, 2000
                       6                                                                                                                                     ESSENTIAL DRUGS MONITOR




                           NEWSDESK




                       New public health channel piloted in Africa
                                orldSpace Foundation and               by making use of the most affordable,                  the AfriStar satellite directly to comput-          WorldSpace Foundation works with

                       W        SATELLIFE have announced a
                                new health service that will pro-
                                vide a steady stream of material
                                                                       efficient and appropriate technology”,
                                                                       states SATELLIFE Executive Director,
                                                                       Holly Ladd. “The Public Health Chan-
                                                                                                                              ers. TheWorldSpace system transcends
                                                                                                                              the difficulties of unreliable telephone
                                                                                                                              systems at a fraction of the cost of most
                                                                                                                                                                               NGOs and other humanitarian groups to
                                                                                                                                                                               bring life-saving information to people
                                                                                                                                                                               who are disadvantaged by poverty, rural
                       to assist medical professionals in Africa       nel will employ the technology of the                  Internet-based projects.                         location and the digital divide. ❏
                       in the diagnosis, prevention and treatment      WorldSpace system to exponentially in-
                       of prevalent diseases. The service, called      crease the amount of information health
                       the Public Health Channel, aims to over-        practitioners throughout Africa can                      SATELLIFE is an international not-for-profit humanitarian organization. Its mission is to
                       come the barriers of poverty, geography         access – information that most health                    improve health by improving connections between professionals in the field, through
                       and unreliable communications infra-            practitioners in the United States and                   electronic communications and information exchange in the areas of public health,
                       structures, to help stop the rise of diseases   Europe take for granted.”                                medicine and the environment. Particular emphasis is on areas of the world where
                       such as malaria, tuberculosis and HIV/              The Public Health Channel will be                    poor communications, economic conditions or natural disasters limit access.
                       AIDS.                                           launched in four countries: Ethiopia,                    SATELLIFE produces two e-mail publications, HealthNet News and HealthNet News–
                           “The ability to widely disseminate          Kenya, Uganda and Zimbabwe. After an                     AIDS, which feature materials from 21 journals, including the British Medical Journal,
                       information about the treatment and pre-        initial test period, the project will expand             Lancet and East African Medical Journal.
                       vention of HIV/AIDS and other diseases          to other African countries, as funding                   SATELLIFE also operates and maintains several global electronic discussion groups
                       is the reason the WorldSpace system             becomes available. WorldSpace receivers                  on subjects relevant to developing countries. (See Netscan page 32 for more
                       was created,” says Gracia Hillman,              will be placed in hospitals, medical                     information on SATELLIFE’s services).
                       WorldSpace Foundation President.                schools, medical libraries, health clinics,              WorldSpace Foundation is a non profit organization created in 1997. Based in
                           “The goal of SATELLIFE’s informa-           health ministries and research settings.                 Washington DC, USA, its work encompasses Africa, Asia-Pacific, Latin America and
                       tion services is to connect the health              WorldSpace receivers provide crystal                 the Caribbean. It has 5% of the channel capacity of the three WorldSpace
                       practitioner in the developing world            clear digital audio channels, and can also               Corporation satellites for non commercial social development and distance learning
                       with a range of high-quality information        serve as a modem, downloading text-                      programming.
                       resources in a cost-effective manner,           based material and dynamic images from




                       Drug donations problem                                                                                 Update on drug donations
                       in Venezuela                                                                                                   study carried out by Community           ➤ While nurses were the most likely

                                onths after devastating floods and     staff and increase working hours simply                 A      Initiatives Support Services Inter-
                                                                                                                                      national has investigated the
                                                                                                                                                                                 health workers to be in charge of phar-
                                                                                                                                                                                 macies and of selecting, prescribing


                        M
                                                                                                                                      benefits and problems of donated           and dispensing drugs, donors usually
                                landslides left up to 30,000 peo-      to classify what has been received.                                                                       decided the quantity of each drug to
                                                                                                                              drugs at 24 mission health facilities in
                                ple dead or missing and 200,000            Dr Francisco Griffin, Director-                                                                       send.
                                                                                                                              Kenya and Tanzania between 1997 and
                                homeless, the Bolivarian Repub-        General of the Production Service, said
                                                                                                                              1998. It found that:                               Researchers concluded that:
                       lic of Venezuela was being inundated            he thought some companies had deliber-
                       again by a flood of unusable medical aid.       ately sent expired products, considered as             ➤ On average health facilities received          ➤ Donated drugs are more appropriate
                       Harrowing television pictures of the dis-       toxic waste, to evade the cost of having                  four deliveries of donated drugs per            when the recipient, not the donor,
                       aster in December 1999 in the coastal           to deal with them themselves. In 1996                     year.                                           decides which drugs are sent.
                       states of Vargas and Falcon, near Cara-         WHO published interagency guidelines                   ➤ Approximately a quarter of all do-             ➤ As nurses play a central role in drug
                       cas, sparked a massive humanitarian             on drug donations1 in response to increas-                nated drugs had a shelf-life of less than       donations they must understand the
                       response, and tonnes of medicines arrived       ing reports of such problems being caused                 one year.                                       principles of good donation practices.
                       from around the world.                          by inappropriate donations.                            ➤ A quarter of donated drugs were                ➤ There is still a need to promote the
                                                                                                                                 antibiotics.                                    essential drugs concept and use of es-
                           However, health workers helping the             However, Dr Griffin accepted that
                       victims say that huge quantities of medi-       the Service had not anticipated such a                 ➤ Three-quarters of the health facilities          sential drugs lists by both donors and
                                                                                                                                 had sent a list of drugs required to the        recipients. ❏
                       cal aid remain stockpiled in warehouses,        massive international response to the
                                                                                                                                 donor, but only half received drugs
                       and up to 70% will have to be inciner-          landslides. When the disorganized nature                                                                For further information on the study contact:
                                                                                                                                 from that list.                               Dr Eva Ombaka, The Pharmaceutical Pro-
                       ated. A report by the Government’s              of the donations and the “titanic work”
                                                                                                                              ➤ When donated drugs were not re-                gramme, World Council of Churches/
                       Pharmacological Production Service says         required to sort through them became
                                                                                                                                 quested by the health facility it was         Community Initiatives Support Services Inter-
                       many products cannot be used because            clear, advertisements were belatedly                                                                    national, P.O. Box 73860, Nairobi, Kenya.
                                                                                                                                 more likely that good drug donation
                       they are out of date, unnecessary, have         posted on the Web sites of international
                                                                                                                                 practices were not adhered to.                Source: Practical Pharmacy, No. 14, 1999.
                       been partially used, or have no Spanish         organizations asking only for specifically
                       labelling. As a result, the Government has      requested products.* ❏
                       already had to spend at least 10m bolivars
                       (approximately US$16,000) to hire extra         Source: BMJ 2000;320:1491.
                                                                                                                              Oxfam campaigns to lower
                                                                                      * There are signs that coun-
                                                                                      tries are beginning to speak
                                                                                                                              drug prices
                                                                                      out, to avoid receiving un-
                                                                                                                                      xfam, the international development agency, is launching a campaign on

                                                                                                                               O
                                                                                      necessary drugs when faced
                                                                                      with disasters. For example,                    access to medicines, with a focus on the issue of affordability. Oxfam has
                                                                                      Mozambique required all                         drawn on its programme experience and local research to produce a number of
                                                                                      donations to be consistent                      reports looking at the determinants of drug prices, and at policies that can
                                                                                      with WHO’s Interagency                  bring them down. It is paying particular attention to the influence of World Trade
                                                                                      guidelines when areas of the            Organization intellectual property rules and to the policies of the pharmaceutical
                                                                                      country were flooded in                 industry, and makes policy recommendations to the main actors.
                                                                                      February and March 2000.                    The British-based organization is seeking to raise public awareness on the issues
Photo: WHO/P. Almsay




                                                                                                                              as part of a broader international campaign to make the world trading system work
                                                                                                                              more to the advantage of poor communities and poor countries. Oxfam has humanitar-
                                                                                                                              ian and development programmes in over 70 low-income countries. It is also a
                                                                                                                              prominent NGO advocate on international economic development issues, including
                                                                                      Reference
                                                                                                                              trade and debt. ❏
                                                                                      1.   WHO. Interagency guidelines for
                       Calm waters on Lake Maracaibo for this auxiliary health             drug donations. Geneva: World      For more information visit Oxfam’s Web site at: www.oxfam.org.uk or e-mail: <tradecampaign@
                       worker doing her rounds, but floods in Venezuela in 1999            Health Organization; 1996.         oxfam.org.uk>. Alternatively, write to George Tarvit, Campaign Department, Oxfam, 274
                       caused massive devastation                                          (Second edition published 1999).   Banbury Road, Oxford, OX2 7DZ, UK.


                                                                                                                                                                                         Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                     7




  ANTIMICROBIAL                             RESISTANCE




Antimicrobial resistance: the facts
                                                                                                 transmission) or through acquisition from       be killed and the infection resolved
           ver the past decade, there has been a dramatic upsurge world wide                     other bacteria of resistance genes (hori-       before resistance has time to emerge.

    O      in the spread of drug-resistant microbes. Major infectious diseases
           such as tuberculosis, pneumonia and malaria are becoming increas-
           ingly difficult and expensive to treat, as microbes develop resist-
                                                                                                 zontal transmission). This dual means of
                                                                                                 acquiring resistance explains why the
                                                                                                 resistance trait can spread rapidly and
                                                                                                                                                 However, in the treatment of chronic
                                                                                                                                                 infections such as TB and HIV/AIDS –
                                                                                                                                                 especially if treatment compliance is
  ance to many of the medicines available. How widespread is the problem?                        replace a previously drug-susceptible           poor – drug-resistant mutants have time
  How does drug resistance develop? And what is WHO doing to contain                             population of bacteria.                         to emerge and multiply and replace
                                                                                                                                                 the drug-susceptible population of
  this threat? Rosamund Williams, Coordinator, Anti-infective Drug Resistance
                                                                                                                                                 microbes. Under these circumstances, it
  and Containment at WHO explains.                                                               Are antimicrobial drugs
                                                                                                                                                 is likely that the treatment outcome will
                                                                                                 to blame?                                       be poor.
                                                                                                      No. Antimicrobial drugs do not cause           So why is it that the microbes in-
    Antimicrobial resistance is on the in-      a year in the United States alone, are al-       resistance. But the process is accelerated      volved in acute infections have also
crease – threatening our ability to treat       most always caused by drug-resistant             when antimicrobials are misused. What           become resistant to many of the first-line
some of the infectious diseases that cause      microbes. Foodborne infections are also          happens is that natural selection
most deaths. Diseases such as tuberculo-        on the increase – promoting growing con-         – a natural biological process –
sis (TB), which was once thought to be          cern about drug resistance in pathogens          favours the survival of microbes
                                                such as Salmonella and Campylobacter.            that develop resistance genes                         PENICILLIN-RESISTANT
under control, are becoming increasingly
                                                                                                 by chance when exposed to                       PNEUMOCOCCI IN THE 1990s
difficult to treat as medicines become less     Meanwhile, tropical diseases, such as
effective – steadily depleting the arsenal      leishmaniasis (see box p.8) and African          antimicrobials. All uses of
of drugs available.                             trypanosomiasis, which haunt the poor            antimicrobials – both appro-                 80 % in hospital patients
    Infectious diseases still account for       and marginalised communities of the              priate and inappropriate – apply
                                                world, are becoming increasingly diffi-          a selective pressure on micro-               70
45% of deaths in low-income countries
and for almost one in two premature             cult to treat among people also infected         bial populations. However, the               60
deaths worldwide. And most of these             with HIV. Treatment with the usual               more antimicrobials are used,
deaths (about 90%) are due to no more           (and sometimes only) drug is increasingly        the greater this pressure will               50

than six diseases: acute respiratory infec-     ineffective.                                     be. Thus it is critical to gain
                                                                                                                                              40
tions (mainly pneumonia), diarrhoeal                                                             maximum benefit from the cura-
                                                How widespread                                   tive effects of antimicrobials –             30
disease, HIV/AIDS, TB, malaria and
                                                is the problem?                                  especially in developing coun-
measles. Antimicrobial resistance is
                                                                                                 tries, where they are not only               20
today challenging our ability to treat              Drug resistance is a global problem –
                                                                                                 misused, but often under-used
effectively at least four of these infec-       affecting both developing and developed                                                       10
                                                                                                 due to financial constraints. At
tions: acute respiratory infections,            countries. Its spread is helped by the enor-
                                                                                                 the same time, it is also essen-              0
diarrhoeal disease, malaria and TB.             mous increase in global travel and trade.
                                                                                                 tial to minimise the opportunities
                                                                                                                                               Isr
                                                                                                                                                Sa l
                                                                                                                                                Eg i Ar
                                                                                                                                                Bu t
                                                                                                                                                Ke aria


                                                                                                                                                H po
                                                                                                                                                M g Ko
                                                                                                                                                Cz ico
                                                                                                                                                Si a




                                                                                                                                                So h R
                                                          Documented examples include:




                                                                                                                                                  on re
                                                                                                                                                  ng


                                                                                                                                                  ex n
                                                                                                                                                  ae
                                                                                                                                                  ud
                                                                                                                                                  yp ab




                                                                                                                                                   ut ep
                                                                                                                                                   ny
                                                                                                 for resistance to emerge. In
                                                                                                                                                   lg




                                                                                                                                                   ec
                                                                                                                                                     a




                                                                                                                                                     h
                                                                                                                                                       Ko ubl
                                                          ➤ cases of drug-resistant gon-         practice this means using




                                                                                                                                                         re ic
                                                                                                                                                          g
                                                                                                                                                           ia




                                                                                                                                                           a
            DECLINING RESPONSE TO                             orrhoea acquired by tourists       antimicrobials both widely
              ANTIMALARIAL DRUGS                              visiting South-East Asia and       and wisely – neither too little,
                                                              transmitted among commu-           nor too much, and never inap- Source: Collected from published data
                                                              nities in Australia;               propropiately. Inappropriate
     100%
                                                          ➤ outbreaks of multidrug-              prescribing practices – including                  drugs available? The problem is that
                       Mefloquine
                                                              resistant TB in Western Eu-        the wrong choice of drug and incorrect             antimicrobial drugs not only kill the
        80                                                                                       dosage or length of treatment – poor               microbe being targeted, they also “treat”
                                                              rope traced back to Eastern
                      Sulfa




                             Quin                                                                compliance with treatment, and the use             other normally harmless microbes
                                  ine                         European countries where
        60                                                                                       of low quality (sometimes counterfeit)             (“normal flora”) in the body as well.
                        doxi




                                                              TB control is poor;
                                                                                                 drugs all contribute to the emergence of           For example, Streptococcus pneumoniae,
                         ne-P




        40                                                ➤ two outbreaks of MRSA                drug-resistant microbes.                           as well as causing otitis, pneumonia
                              yrim
              Ch




                                                              (methicillin-resistant Sta-                                                           and meningitis, is also carried by many
                lor


                               ethin




                                                              phylococcus aureus) hospital
                 oq




        20                                                                                                                                          people, especially children, as part of
                                                                                                 How does resistance
                   uin




                                                              infection in Canada involv-
                                 e




                                                                                                                                                    their normal throat flora, without caus-
                      e




                                                              ing patients who acquired the      develop?
         0                                                                                                                                          ing any symptoms. So every time they
                                                              strain in India.
               1976    1980   1984    1988   1992                                                     If a person develops an acute infec-          take an antimicrobial – for whatever
                                                              In addition, cases of drug-        tion such as pneumonia with a drug-                reason – their streptococci are exposed.
Source: The Southeast Journal of Tropical Medicine and resistant malaria occur among             susceptible strain of Streptococcus                If a mutant emerges, it will have a selec-
Public Health, Mekong Malaria, Volume 30, Supplement 4, travellers returning to developed        pneumoniae, for example, and is treated            tive advantage and can spread to other
p 68, 1999                                                countries from malaria-endemic         promptly with penicillin, the bacteria will        people. A similar process occurs when
                                                          countries where re-                                                                       salmonella bacteria are exposed to
    Chloroquine, for example – once the         sistance is high. These drug-                                                                       antimicrobials incorporated into ani-
first-line treatment for malaria – is no        resistant infections will not                                                                       mal feed. While these bacteria may
longer effective in 81 of the 92 countries      spread in developed countries               THE PARADOX OF CONTROLLING                              not cause the animal any harm, they can
where the disease is a public health prob-      provided there are no mosquito                         DRUG RESISTANCE
                                                                                                                                                    be spread to humans through the food
lem. In some regions, over half of all cases    vectors. But global warming                Antibiotics too      Undertreatment and inadequate       chain.
of streptococcal pneumonia are resis-           could change all that.                    readily available           access to antibiotics
tant to penicillin. And over 20% of new
TB cases are now multidrug-resistant.                                                                                                               What is multidrug-
                                                What is antimicrobial                                                                               resistance?
    To make matters worse, resistance
                                                resistance?
is already emerging to anti-HIV drugs.                                                                        Encourages                                There are many different classes
There are reports of resistance to all              When antimicrobial resist-                                 resistance                           of antimicrobials, and microbes have
currently marketed antiretroviral drugs.        ance occurs, it is the microbe                                                                      devised ways to resist the action of
And resistance is also widespread among         (bacterium, virus, fungus or pro-                                                                   each and every one. In addition, a single
sexually-transmitted infections, such as        tozoan) that is resistant; not the                                                                  microbial cell can carry resistance
gonorrhoea, that enhance the spread of          drug, nor the patient. Species of                                                                   genes to a whole series of totally
HIV.                                            bacteria that are normally resist-                        Resistant infections
                                                                                                                                                    unrelated antimicrobial drugs. Over
    But the problem does not end there.         ant to penicillin, for example, can                       not properly treated
Hospital-acquired (nosocomial) infec-           develop resistance to these drugs
tions, which account for 40,000 deaths          either through mutation (vertical Source: World Health Organization/CDS                                                 ...cont’d on page 8 ➠


Issue No. 28 & 29, 2000
8                                                                                                                                ESSENTIAL DRUGS MONITOR




  ANTIMICROBIAL                              RESISTANCE


Antimicrobial resistance...                      TACKLING          THE    PROBLEM
cont’d from pg. 7
                                              Can antimicrobial
                                              resistance be halted?
                                                                                                                 The example of leishmaniasis
time, the dysentery-causing bacterium                                                               Leishmaniasis is an insect-borne disease that is showing resistance to the highly
                                                 No. But it can be contained. Antimi-
Shigella, for example, has become                                                                   toxic, heavy metal-based antimonials at rates of 64% in some developing nations.
                                              crobial resistance is a natural biological            Currently, visceral leishmaniasis – otherwise known as Kala-azar – afflicts 500,000
resistant to each successive class            phenomenon – the response of microbes                 people each year in 61 countries in East Africa, India and the Mediterranean basin.
of antimicrobials used in treatment. As       subjected to the selective pressure of an-            The sandfly-transmitted parasite attacks the spleen, liver and bone marrow and is
a result, it has a string of genes, each      timicrobial drug use. The main priority               characterised by fever, severe weight loss and anaemia. Left untreated, the disease
                                                    should be to prevent infection in the           is fatal. Drug-resistant leishmaniasis results when treatment courses are too short,
                                                    first place. After that, containment            interrupted, or consist of poor-quality or counterfeit drugs. Once infected, victims
                                                    of the problem is the best we can               remain vulnerable to potentially fatal flare-ups throughout their life. As with most
                                                    aim for. And since it is antimicro-             infectious diseases, resistant strains flourish in areas where poverty is high, surveil-
                                                    bial use that drives resistance, the            lance is low and treatment frequently inconsistent due to limited medical access,
                                                    focus of any containment strategy               inadequate diagnosis, the availability of parallel-market drugs, and political discord.
                                                                                                    Active monitoring procedures that could reveal the true extent of the disease are
                                                    should be on minimising any
                                                                                                    hindered by lack of available funds and civil unrest. In one study, WHO researchers
                                                    unnecessary, inappropriate or irra-
                                                                                                    conducting a house-to-house search discovered that the actual rate of infection was
                                                    tional use of antimicrobial drugs.              48 times that which had been initially reported.
                                                    Many groups of people play a role
                                                    in determining how and where                    In the State of Bihar in north-western India, up to 70% of cases are non-responsive to
                                                    antimicrobials are used:                        current treatments, while in Bangladesh, Brazil – and particularly Sudan (where 90%
                                                                                                    of all cases originate), resistance continues to grow. In developed Mediterranean
                                                    ➤ patients and the general public;              nations, drug-resistant leishmaniasis is spreading as the number of patients co-
                                                    ➤ all groups of prescribers and                 infected with HIV increases. Those infected with HIV or who are immuno-suppressed
                                                      dispensers;                                   in any way (as a result of cancer treatments or organ transplants) are likewise
                                                                                                    vulnerable. Any kind of immuno-suppression can potentially increase the number of
                                                    ➤ hospital managers and health                  parasites in the blood, thereby giving rise to the likelihood of transmission through
                                                      care professionals;                           the bite of the sandfly. This cycle facilitates a destructive spiral of greater resistance,
                                                    ➤ users of antimicrobials in                    higher parasitic levels and increased infection-producing potential.
                                                      agriculture;                                  War, globalisation, increased travel and climatic change places this parasitic
                                                    ➤ national governments;                         infection solidly in the category of emerging diseases with rapidly-evolving
                                                                                                    resistance.
                                                    ➤ pharmaceutical, diagnostic and
                                                      “surveillance” industries;
                                                                                                Source: WHO. Overcoming antimicrobial resistance. Geneva: World Health Organization; 2000.
                                                    ➤ international agencies, NGOs,
                                                      professional societies.
                                                       All of these groups need to be engaged                                                                                                  A female patient
                                                    in developing and implementing a resistance                                                                                                with Leishmania
                                                                                                                                                                                               aethiopica
                                                    containment action plan.                                                                                                                   infection


                                                    What is WHO doing?
                                                       WHO has taken the lead in developing a
                                                    Global Strategy for the Containment of Antimi-
                                                    crobial Resistance. The strategy is designed to
Source: World Health Organization/CDS
                                                    reduce the emergence of resistance and slow the
                                                    spread of resistant infections, in an effort to re-
coding for resistance to a different anti-          duce the mortality, morbidity, and high costs
microbial. To make matters worse, this
string of genes can be transmitted from
one bacterial cell to another. Thus a
                                                              RESISTANCE CAN BE
previously susceptible Shigella can, in                      EFFECTIVELY TREATED
one fell swoop, acquire five or six
resistance genes.                                 Ideal drug usage involves:
                                                  • The correct drug
                                                  • Administered by the best route
Why is antimicrobial                              • In the right amount
                                                  • At optimum intervals
resistance spreading                              • For the appropriate period
so fast?                                          • After an accurate diagnosis

    Although mutations are rare events            Problems occur in both developed and developing
                                                                                                                                                                              Photo: WHO/TDR




                                                  countries when antimicrobials are:
(about one in a million bacteria may              • Not equitably available
show a mutation which might lead                  • Used by too many people
to resistance), microbes multiply                 • To treat the wrong disease
                                                  • In the wrong dosage
very rapidly – thereby enabling a single          • For the wrong period of time
mutant to rapidly become dominant.                • Not in the correct formulation or strength
                                                                                                              associated with antimicrobial resistance. The strategy is based on pub-
Microbes also spread readily from
                                                  Antimicrobial resistance is not a new or surprising         lished evidence, expert opinion, and the deliberations of other expert bodies.
person to person. Thus one patient in-
                                                  phenomenon. All micro-organisms have the ability            It includes a review of the factors responsible for the emergence and spread
fected with a resistant strain may be an          to evolve various ways of protecting themselves
                                                                                                              of resistance and of the interventions that have been tested or proposed to
important source of spread, not only of           from attack BUT over the last decade or so:
                                                  • Antimicrobial resistance has increased                    address the problem. The strategy provides a framework of interventions
the infection, but of a resistant infec-
                                                  • The pace of development for new and replacement           for implementation. It also highlights the gaps in current knowledge and
tion. This is demonstrated in hospitals,          antimicrobials has decreased                                the many outstanding research needs. Foremost among these is the need to
where one patient infected with MRSA,
                                                  RESISTANCE MEANS THAT:                                      develop new drugs to combat drug-resistant infections, and to develop a
for example, is often the source from
                                                  • People can’t be effectively treated                       new environment of incentives and public-private partnerships to address
which many others become infected or              • People are ill for longer                                 the challenges of antimicrobial resistance. ❏
colonised.                                        • People are at greater risk of dying
    Thus in taking action to contain              • Epidemics are prolonged
                                                  • Others are at greater risk of infection
resistance, both the emergence of resist-                                                                     For further details contact: Dr Rosamund Williams, Communicable Diseases Clus-
ance and the spread of resistant strains                                                                      ter, Anti-infective Drug Resistance and Containment, World Health Organization,
need to be considered.                        Source: World Health Organization/CDS                           1211 Geneva 27, Switzerland.


                                                                                                                                                              Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                                                  9




  ANTIMICROBIAL                                            RESISTANCE




Who contributes to
misuse of antimicrobials?
                                           ➢ KATHLEEN HOLLOWAY*                                                                the time), they are still Figure 2
                                                                                                                               greatly influenced by pa- Adequacy of diagnostic process
      ntimicrobial resistance is a natural consequence of antimicrobial use,                                                   tients’ demands. Many tra-

  A   which kills the sensitive organisms leaving the resistant ones to survive                                                ditional practitioners are now
                                                                                                                                                                       Pakistan
      and multiply (selection of resistance). Overuse and misuse of antimicrobials                                             prescribing allopathic me-
                                                                                                                               dicines instead of herbal or         Bangladesh
      do not help patients, they merely add to the problem of resistance
and waste resources.                                                                                                           other kinds of medicines be-        Burkina Faso
                                                                                                                               cause this is what patients              Senegal
Prescribers                                                                     information, leading to uncertainty            want. In Tanzania 60% of
                                                                                                                                                                         Angola
                                                                                about the diagnosis and the most               health workers admitted to
    There is a wide variation in the pre-                                                                                                                              Tanzania
                                                                                appropriate drug(s), and fear of poor          prescribing inappropriate
scribing of antimicrobials and other
                                                                                patient outcome                                drugs demanded by socially                        0         10          20         30          40          50      60
drugs. In primary health care 30–60% of
                                                                            ➤ patient demand                                   influential patients, to avoid
patients receive antibiotics (see Figure 1),                                                                                                                                   % observed consultations where the diagnostic process was adequate
                                                                            ➤ earning a living through selling                 being labelled “difficult”.6
perhaps twice what is clinically needed.
                                                                                medicines.                                     Many people in India believe
Misuse is common and may take the form
                                                                                                Many prescribers in de-        in ‘tonics’ and will not return Sources: Thaver et al, Social Science and Medicine 1998. Guyon
                                                                                                                                                                et al, WHO Bulletin 1994. Krause et al, Tropical Medicine and
Figure 1                                                                                   veloping countries have             to a doctor unless he or she International Health 1998. Bitran, Health Policy and Planning
Percentage of primary health care patients                                                 little access to good quality       prescribes according to their 1995. Bjork et al, Health Policy and Planning 1992, Kanji et al,
                                                                                           information about diagnosis         wishes. Even though doctors Health Policy and Planning 1995.
receiving antibiotics
                                                                                           and drugs. Standard treat-          may know that ‘tonics’ are
                      AFRICA
                                                                                           ment guidelines are often           ineffective, they prescribe them because               of antibiotic purchases were for 10 or
                       Sudan                                                               unavailable and health              they are dependent on the patient return-              fewer capsules, which in most circum-
                  Swaziland                                                                workers are often unsup-            ing for their livelihood.7 In Europe, over             stances would be less than a full course.
                  Cameroon                                                                 ported and unsupervised.            50% of mothers interviewed in a study                       In conclusion, antibiotics are often
                       Ghana
                                                                                           Frequently, drug company            expected to receive antibiotics for most               prescribed irrationally (over-prescription
                    Tanzania
                  Zimbabwe
                                                                                           representatives are doctors’        respiratory infections.8                               and inappropriate prescription) and
                        ASIA                                                               only source of information.             Prescribers citing patient demand as               this contributes to the development of
                   Indonesia                                                               Such information may well           a cause of irrational prescribing has been             antimicrobial resistance. However, pre-
                       Nepal                                                               be biased, particularly with
                 Bangladesh
                                                                                                                               reported in many countries. And patient                scribers may have very rational reasons
                                                                                           regard to how effective their       demand for specific drugs has been                     for prescribing irrationally and it is not
  LATIN AMERICA & CARIBBEAN
          Eastern Caribbean
                                                                                           company’s drug is com-              widely observed by researchers. How-                   just a question of lack of knowledge. Only
                 El Salvador                                                               pared to rival drugs of the         ever, the degree to which prescribers are              by understanding the reasons underlying
                     Jamaica                                                               same class. Uncertainty of          influenced by their patients is unknown                inappropriate prescribing can one design
                 Guatemala                                                                 the diagnosis, fear of poor         and probably varies according to the skills            effective interventions to change such
                                                                                           patient outcome, (and in in-        and confidence of the prescriber. There                behaviour. ❏
                             0% 10%    20%      30%       40%       50%      60%   70%
                                                                                           dustrialised countries, fear
                                    % of PHC patients receiving antibiotics                                                    is some evidence that it is a prescriber’s
                                                                                           of litigation), lead to over-                                                              * Dr Kathleen Holloway is a Medical Of-
                                                                                                                               perception of patient demand, rather                   ficer in the Department of Essential Drugs
Source: Managing Drug Supply, 2nd ed. Quick JD, Rankin JR,                                 presciption of antibiotics. In
                                                                                                                               than actual patient demand, during the                 and Medicines Policy at the World Health
Laing RO, O’Connor RW, Hogerzeil HV, Dukes MN, Garnett A,                                  many developing countries,
                                                                                                                               consultation process that may affect the               Organization.
eds. Hartford CT: Kumarian Press; 1997.                                                    the diagnostic process is
                                                                                                                               prescribing decision.9,10
                                                                                           often inadequate to arrive at                                                                    References
of incorrect dosage or inappropriate pre-                                   a diagnosis with any certainty (Figure 2).                                                                      1.  Gilson L, Jaffar S, Mwankusye S, Teuscher T. Assessing

scription. In Tanzania, 91% of antibiotics                                                                                     Effects of                                                       prescribing practice: a Tanzanian example. International
                                                                                                                                                                                                Journal of Health Planning and Management 1993;8:
were prescribed with incorrect dosage1                                      Patient demand or                                  dispensing doctors                                               37–58.
                                                                                                                                                                                            2. Uppal R, Sarkar U, Giriyappanavar Cr, Kacker V. Anti-
and in India over 90% of prescriptions                                      prescriber perception?                                 Many prescribers, as well as drug                            microbial drug use in primary health care. Journal of
did not have dose specifications.2 Inap-                                        Even if prescribers are certain of their       retailers, earn their living by selling                          Clinical Epidemiology 1993;46(7):671–673.
                                                                                                                                                                                            3. Hui L, Li X.S, Zeng X.J, Dai Y.H, Foy H.M. Patterns
propriate prescription of antibiotics has                                   diagnoses (and none of them will be all            medicines and not by charging a consul-                          and determinants of use of antibiotics for acute respira-
been reported to occur for vi-                                                                                                 tation fee. It has been shown in many                            tory tract infection in children in China. Paediatric
                                                                                                                                                                                                Infectious Disease Journal 1997;16(6):560–564.
ral respiratory tract infections Table 1                                                                                       countries that prescribers who earn                          4. Bosu W.K, Afori-Adjei D. Survey of antibiotic prescrib-
in 97% of cases in China3 and Inappropriate use of antibiotics in                                                              money from dispensing medicines                                  ing patterns in government health facilities of the Wassa
                                                                                                                                                                                                West District of Ghana. East African Medical Journal
81% of cases in Ghana.4 In-                                                                                                    consistently prescribe more drugs than
                                                      teaching hospitals                                                                                                                        1997;74(3):138–142.
appropriate prescription of                                                                                                    those who do not make money from                             5. Nizami S, Khan I, Bhutta Z. Drug prescribing practices
                                                                                                                                                                                                of general practitioners and paediatricians for childhood
antibiotics for childhood di-                                                                                                  dispensing. In a study in Zimbabwe11
                                                           Country                  Inappropriate Type/department                                                                               diarrhoea in Karachi, Pakistan. Social Science and
arrhoea commonly occurs, as                                                         use (%)                                    dispensing doctors prescribed antibiotics                        Medicine 1996;42(8):1133–1139.
                                                                                                                                                                                            6. Mnyika K.S, Killewo J.Z.J. Irrational drug use in Tanza-
reported in Pakistan. Here pri-                                                                                                to 58% of their patients compared to                             nia. Health Policy and Planning 1991;6(2):180–184.
vate general practitioners were                            Canada 1977              42%            Surgical ward –             non-dispensing doctors who prescribed                        7. Nichter M, Pharmaceuticals, health commodification
                                                                                                     injections, antibiotics                                                                    and social relations: ramifications for primary health
found to prescribe significantly                                                                                               antibiotics to 48% of their patients.                            care, Anthropology and International Health, South Asian
more antibiotics (41% of pae-                                                       50%            Gynaecology ward                                                                             Case Studies 1989; Section 3, No.9:233–277. (Kluwer
                                                                                    12%            Medical ward                In China, after the ‘socialist market                            Academic Publishers).
diatric cases) than paedia-
                                                           USA 1978                 41%            All patients                economy’ reforms of the late 1970s, drug                     8. Branthwaite A, Pechere J-C. Pan-European survey of
tricians (36% of paediatric                                                                                                                                                                     patients’ attitudes to antibiotics and antibiotic use. Jour-
                                                           Australia 1979           86–91%         Prophylaxis                 sales became an important source of
cases) in the public hospitals.5                                                                                                                                                                nal of International Medical Research 1996;24(3):
                                                           Canada 1980              30%            Paediatric medical cases    income for providers, including health                           229–238.
      Hospital prescribers are of-                                                  63%            Paediatric surgical cases                                                                9. Britten N, Ukoumunne O. The influence of patients’
ten the role models for primary                                                                                                worker salary supplements. Once drug                             hopes of receiving a prescription on doctors’ perceptions
                                                           Australia 1983           48%            All departments
health care prescribers. Unfor-                                                                                                sales formed part of health worker sala-                         and the decision to prescribe: a questionnaire survey.
                                                           Kuwait 1988              39%            Paediatric inpatients                                                                        British Medical Journal 1997;315:1506–1510.
tunately, antimicrobials are                               Australia 1990           64%            Patients on vancomycin      ries, greater polypharmacy was observed,                     10. Paredes P, de la Pena M, Flores-Guerra E, Diaz J, Trostle
misused just as much in hospi-                             Thailand 1990            91%            All departments             and the average prescription was found                           J. Factors influencing physicians’ prescribing behaviour
                                                                                                                                                                                                in the treatment of childhood diarrhoea: knowledge
tals as in primary health care,                            South Africa 1991        54%            Gynaecology inpatients      to cost two to six times the average per                         may not be the clue. Social Science and Medicine
as shown in Table 1.                                                                22–100%        Unrestricted antibiotics    capita daily income.12 Selling high cost                         1996;42(8):1141–1153.
                                                                                                                                                                                            11. Trap B, Hansen E.H, Hogerzeil H.V. Prescribing by dis-
      Why do providers prescribe                           Thailand 1991            41%            All departments             items, such as antibiotics, may earn                             pensing and non-dispensing doctors in Zimbabwe.
                                                                                    79.7%          Surgical prophylaxis                                                                         Copenhagen: Royal Danish School of Pharmacy; 2000.
antimicrobials too often and                                                                                                   dispensing prescribers more profit, but
                                                                                    40.2%          Documented infection                                                                         (Unpublished study).
unnecessarily? There are many                                                                                                  unfortunately many patients cannot afford                    12. Shao-Kang Z, Sheng-Ian T, You-de G, Bloom G. Drug
causes including:                                                                                                              such drugs and may buy incomplete                                prescribing in rural health facilities in China: implica-
                                                      Source: Hogerzeil HV. British Journal of Clinical                                                                                         tions for service quality and cost. Tropical Doctor
➤ lack of knowledge or Pharmacology 1995;39:1–6.                                                                               courses. In a study in the Philippines 90%                       1998;28:42–48.



Issue No. 28 & 29, 2000
                          10                                                                                                                              ESSENTIAL DRUGS MONITOR




                            ANTIMICROBIAL                                RESISTANCE




                          Problems from antimicrobial
                          use in farming
                                                              ➢ KLAUS STÖHR*                                                    many countries, people who are inad-
                                                                                                                                equately trained dispense them. One         Examples of the
                                 ollowing their success in human medicine, antimicrobials have been                             study reported that more than 90% of        consequences of overuse

                            F    increasingly used to treat disease in animals, fish and plants. They also
                                 became an important element of intense animal husbandry because of
                                 their observed growth enhancing effect, when added in sub-therapeutic
                                                                                                                                the drugs used in animals in the United
                                                                                                                                States in 1987 were administered
                                                                                                                                without professional veterinary con-
                                                                                                                                                                            ◆ Shortly after the licensing and use
                                                                                                                                                                               of fluoroquinolone, a powerful
                                                                                                                                                                               new class of antimicrobials, in
                          doses to animal feed. Some growth promoters belong to groups of antimicrobials                        sultation. Inappropriate doses and             poultry, fluoroquinolone-resistant
                          (for example, glycopeptides and streptogramins), which are essential drugs                            combinations of drugs are frequently           Salmonella and Campylobacter
                          in human medicine for the treatment of serious, potentially life-threatening                          used in animals. And antimicrobials            isolations from animals, and soon
                                                                                                                                administered to animal flocks and              afterward from humans, became
                          bacterial diseases. These include Staphylococcus or Enterococcus infections.                                                                         more common. Community and
                                                                                                                                herds in their feed causes problems of
                                                                                                                                inaccurate dosing, and the inevitable          family outbreaks, as well as
                              The widespread use of antimicrobials          Scale of use                                        treatment of all animals irrespective
                                                                                                                                                                               individual cases, of Salmonellosis
                          in farming is of serious concern as some                                                                                                             and Campylobacteriosis resistant
                                                                                The total amount of antimicrobials              of health status.                              to treatment with fluoroquinolones
                          of the newly emerging resistant bacteria          used in food animals is not precisely                                                              have since been reported from
                          in animals are transmitted to humans,             known, although it is estimated that about       ➤ Empiric treatment predominates                  several countries.
                          mainly from food of animal origin or              half of the antimicrobials produced glo-           because of the widespread lack of
                          through direct contact with farm animals.                                                            diagnostic services, particularly in de-     ◆ With the emergence of vancomy-
                                                                            bally are used in farming, particularly in
                          Treating disease caused by these resist-                                                                                                             cin-resistant strains of Staphylo-
                                                                            pig and poultry production.                        veloping countries. In many places,
                                                                                                                                                                               coccus and Enterococcus bacteria
                          ant bacteria in humans is more difficult              In Europe, all classes of antimicrobial        it is uncommon to submit clinical               in many hospitals around the
                          and costly and, in some cases, available          licensed for disease therapy in humans are         specimens and samples from sick ani-            world, the question arose if the
                          antimicrobials are no longer effective.           also registered for use in animals, a situ-        mals, due to the costs involved, time           use of those antimicrobial agents
                          The best-known examples are diseases              ation comparable with other regions in the         restrictions and the limited number of          in agriculture could have com-
                          caused by the foodborne pathogenic bac-           world, although comprehensive regis-               laboratories.                                   pounded the worsening problem.
                          teria Salmonella and Campylobacter and            tration data are much more difficult to                                                            Vancomycin-resistant Enterococci
                                                                            obtain. National statistics on the amount        ➤ Drug sales constitute a significant por-        were isolated in animals, food
                          the commensal (harmless in healthy
                                                                            and pattern of antimicrobial use, in hu-           tion of veterinarians’ income in some           and non-treated volunteers in
                          persons and animals) bacteria Enterococ-                                                                                                             countries where vancomycins were
                          cus. Research has shown that resistance           man medicine or anything else, exist in            countries and may lead to unnecessary
                                                                                                                                                                               also used as growth promoters in
                          in these bacteria is often a consequence          only a few countries.                              prescribing.                                    animals. By 1997 all European
                                                                                An average of 100 milligrams of                                                                countries had banned vancomy-
                          of using certain antimicrobials in
                                                                            antimicrobials are used in animals in Eu-        ➤ In many countries, including several            cin, and after this the prevalence
                          agriculture.
                                                                            rope to produce one kilogram of meat for           developed ones, antimicrobials are              of resistant Enterococci in animals
                              More studies are needed, however, as
                                                                            human consumption. Statistics from other           available over-the-counter and may be           and food, particularly in poultry
                          the impact of the widespread distribution         regions are scarce, but increased meat                                                             meat, fell sharply.
                                                                                                                               purchased without prescription.
                          of non-metabolised antimicrobials                 production in many developing countries
                          through manure and other effluents into           is mainly due to intensified farming,            ➤ Inefficient regulatory mechanisms
                          the environment is still unknown. And             which is often coupled with greater anti-          or poor enforcement, with lack of          How to tackle
                          information is also scarce on the type and        microbial use for both disease therapy and         quality assurance and marketing of         the problem
                          amount of antimicrobials used in the ex-          growth promotion.                                  substandard drugs, are important
                          panding aquaculture sector. Based on the                                                             contributory factors. Discrepancies           WHO, the UN Food and Agriculture
                          lessons learned from species living on            Factors contributing                               between regulatory requirements and        Organization, the Office International
                          land, there is an urgent need to review           to overuse                                                                                    des Epizooties and 14 other international
                                                                                                                               prescribing/dispensing realities are
                          current practices to identify potential haz-                                                                                                    governmental and nongovernmental or-
                                                                            ➤ Education on antimicrobial resistance            often wider than in human medicine.
                                                                                                                                                                          ganizations and professional societies
                          ards. This also applies to other uses of             and prudent antimicrobial use is                                                           have developed a framework of recom-
                          antimicrobials, in plant protection and in           lacking amongst dispensers and pre-           ➤ Antimicrobial growth promoters are
                                                                                                                                                                          mendations to reduce the overuse and
                          industry, for example.                               scribers of antimicrobials, and in              not considered drugs and are licensed,
                                                                                                                                                                          misuse of antimicrobials in food animals
                                                                                                                               if at all, as feed additives.
                                                                                                                                                                          for the protection of human health.
                                                                                                                                                                          (For further information see: http://www.
                                                                                                                             ➤ As in human medicine, pharma-
                                                                                                                                                                          who.int/emc/diseases/zoo/who_global_
                                                                                                                               ceutical industry marketing of
                                                                                                                                                                          principles.html).
                                                                                                                               antimicrobials influences veteri-
                                                                                                                               narians’ and farmers’ prescribing          What the various stakeholders
                                                                                                                               behaviour and use patterns. There are      need to do
                                                                                                                               currently few countries with industry
                                                                                                                               codes or government rules for over-        Responsibilities of regulatory
                                                                                                                               seeing advertising practices for           and other relevant authorities
                                                                                                                               antimicrobials for non human use.              All antimicrobials used in food ani-
                                                                                                                                                                          mals should be reassessed in relation to
                                                                                                                             ➤ There is a significant increase in         their propensity to cause antimicrobial
                                                                                                                               intensive animal production, particu-      resistance in bacteria which can be trans-
                                                                                                                               larly in countries with economies in       mitted to humans. Priority should be
Photo: WHO/PAHO/A. Waak




                                                                                                                               transition where all the factors listed    given to those products considered most
                                                                                                                               here are present. When animal pro-         important in human medicine.
                                                                                                                                                                              After the licensing of veterinary
                                                                                                                               duction appears to benefit from the use
                                                                                                                                                                          antimicrobials, surveillance of resistance
                                                                                                                               of antimicrobials, economic incen-
                                                                                                                                                                          to antimicrobials belonging to classes
                                                                                                                               tives may take precedence over the         considered important in human medicine
                                                                                                                               possible transfer of resistance to hu-     should be conducted. In this way emer-
                          A butcher’s stall in the Dominican Republic. There is increasing evidence of the problems caused     mans, and the potential negative           gence of antimicrobial resistance will
                          by feeding antimicrobials to farm animals                                                            impact on human health.                    be detected in time to allow corrective

                                                                                                                                                                                  Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                    11




  ANTIMICROBIAL                                RESISTANCE




                                                Promoting resistance?
Farming... cont’d from pg. 10
strategies to be implemented as part of
an efficient post-licensing review.
    Authorities should ensure that all
antimicrobials for disease control in ani-                                          ➢ JOEL LEXCHIN*                                               of this ad to interpret those words to
mals are classified as prescription-only
                                                                                                                                                  mean that clarithromycin has clinically
medicines.
                                                        he Autumn 1996 issue of Health Horizons, the magazine of the Interna-                     important advantages over alternative
Distribution/sales/marketing
    Enforcement policies should be
designed to ensure compliance with
                                                  T     tional Federation of Pharmaceutical Manufacturers Associations, ran a
                                                        two-page feature entitled “International Mobilization Against New and
                                                        Resistant Diseases.” This article highlighted the efforts being made by
                                                                                                                                                  antimicrobials and thus was a first line
                                                                                                                                                  antibiotic for common childhood in-
                                                                                                                                                  fections. As MaLAM pointed out, autho-
laws and regulations on the authori-            international organizations and the pharmaceutical industry to deal with the                      ritative sources did not recommend
sation, distribution and sale, and use          threat of increasing antibiotic resistance. What the article didn’t mention was                   clarithromycin as the treatment of choice
of antimicrobials. They should aim at           that some in the industry can also play a role in promoting bacterial resistance                  for paediatric otitis media, pharyngitis
preventing the illicit manufacture,             to currently available medications.                                                               or sinusitis. The parallels with the Cana-
importation, and sale of antimicro-                                                                                                               dian example of the advertisement for
bials, and at controlling their distribution        According to one company, cipro-            that otitis media, at least in children older     ciprofloxacin are clear; the advertise-
and use.                                        floxacin is “an appropriate choice for your     than two years, should not be treated             ments are encouraging the overuse of
    Special attention should be paid to         [doctors’] patients at risk.” This was the      with antibiotics unless the child fails to        second-line drugs.
the distribution and sale of counterfeit,       message in an advertisement that ap-            improve after 48 hours.                               A couple of American studies, span-
sub-potent and misbranded veterinary            peared in the 3rd October 2000 issue of             What these advertisements do is to            ning almost a quarter of a century, make
antimicrobials. Enforcement action              the Canadian Medical Association Jour-          promote, as first line choices, the use of        the point that the concern about promo-
should be taken to stop such distribu-          nal. “Appropriate” for whom? To answer          antibiotics that should be kept in reserve,       tion leading to the misuse of antibiotics
tion and sale by relevant authorities, in       that question readers had to notice a           and promote the use of antibiotics for            is more than just a theoretical problem.
coordination with the exporting country,        small asterisk after the word “risk” and        conditions that will probably resolve             The first of these, published in the early
if appropriate.                                 then look down to the bottom of the             without any intervention. Both situations         1970s, showed that more appropriate use
                                                page, where in small print they found           represent inappropriate use of antibiotics        of the antibiotic chloramphenicol was
Antimicrobial growth promoters                                                                                                                    related to infrequent use of journal ads to
                                                the definition. “Appropriate” for what?         and clearly have the potential to lead to
    Use of antimicrobial growth promot-                                                                                                           learn about usefulness of new drugs, and
                                                Once again in small type was the an-            increased resistance.
ers that belong to classes of antimicrobial                                                                                                       disapproval of detailers as sources of pre-
agents used (or submitted for approval)         swer; ciprofloxacin should be used in               The other common feature of these
                                                “challenging” respiratory tract infections.     advertisements is that they are for new,          scribing information for new drugs. 1
in humans and animals should be termi-                                                                                                            The second study came out in 1996. In
nated or rapidly phased-out in the absence      Challenging was never defined. In the           expensive antibiotics; drugs that can gen-
                                                same advertisement the company claimed          erate large profits for companies, if sales       this case, researchers presented a group
of risk-based evaluations.                                                                                                                        of primary care doctors with three case
                                                that it supports the appropriate use of         volumes are large. What doctors do not
Surveillance of                                 antibiotics.                                    see is advertising for older, less expen-         scenarios, two of which involved infec-
antimicrobial resistance                            Advertisements that do not give clear       sive antibiotics, even though these drugs         tious diseases, and asked them to choose
                                                information or that give it in print that re-   are the ones that are the most appropri-          between four treatment options of equal
    Programmes to monitor antimicro-
                                                quires the use of a magnifying glass are        ate. When was the last time there was an          efficacy but with widely varying costs.
bial resistance in animal pathogens,
                                                not supportive of appropriate use of me-        ad for penicillin for streptococcal phar-         The more credibility that doctors attached
zoonotic agents (for example, Salmonella
                                                dications. The message in the ad for            yngitis or for trimethoprim for a urinary         to information coming from sales repre-
spp. and Campylobacter spp.), and bac-
teria known to be indicators of anti-           ciprofloxacin is that doctors should feel       tract infection?                                  sentatives the higher the physician’s cost
microbial resistance (for example, Es-          free to use this medication as a first line         This scenario is not limited to Canada,       of prescribing.2
cherichia coli and Enterococcus faecium)        agent any time they are worried about           the situation is, if anything, worse in other         In many cases in developing countries
should be implemented on bacteria from          their patients, or think that there is some-    parts of the world. The Medical Lobby             doctors lack sources of objective infor-
animals, food of animal origin and              thing unusual going on. Ciprofloxacin is        for Appropriate Marketing (MaLAM)                 mation about antibiotics. These doctors
humans.                                         a good first choice for a limited number        has received a number of examples of              are totally reliant on promotional mate-
                                                of problems but not for most respiratory        inappropriate antibiotic promotion in de-         rial from companies, with all of the biases
Surveillance of antimicrobial use               tract infections. The Australian Schedule       veloping countries. Advertisements in             that this material entails. In the mid 1980s
    Information on the amounts of anti-         of Pharmaceutical Benefits restricts the        1994 and 1995 in the Philippines advo-            physicians practicing in a peripheral
microbials given to food animals should         use of this antibiotic in these situations      cated the use of lincomycin for tonsillitis/      health centre in Sri Lanka where poly-
be made publicly available at regular           and the same is true in some Canadian           pharyngitis and clindamycin in upper res-         pharmacy, multiple antibiotic therapy and
intervals, be compared to data from sur-        provinces.                                      piratory tract infections. The most likely        the use of mixtures of unproven efficacy
veillance programmes on antimicrobial               Another recent Canadian journal ad-         cause of any of these conditions is a viral       were common, were totally dependent on,
resistance, and be structured to permit         vertisement, this time for azithromycin,        infection where antibiotics are useless.          and positive towards, drug information
further epidemiological analyses.               had a young baseball pitcher, his face          Once again, antibiotics are being adver-          from drug companies.3
                                                determined, ready to release the ball with      tised for conditions that do not require              Drug companies are now racing to
Prophylactic use of antimicrobials                                                                                                                bring out new, more powerful antibiotics
                                                the message “tough on acute otitis me-          them.
    Use of antimicrobials for prevention                                                                                                          to combat drug resistance, and we should
                                                dia, easy on kids.” The message in this             1997 advertising claims in India
of disease can only be justified where it                                                                                                         welcome these medications. But if the
                                                case was that doctors and their young           for clarithromycin used the words “pae-
can be shown that a particular disease is                                                                                                         industry is sincere about wanting to
                                                patients need a powerful medication             diatric suspension . . . speed, . . . strength,
present or is likely to occur. The routine                                                                                                        do something about resistance then it
                                                to deal with otitis media and that              . . . spectrum, . . . safety” without any
prophylactic use of antimicrobials should                                                                                                         should start by monitoring its promotional
                                                azithromycin fits the bill. However, this       qualification. In MaLAM’s opinion it
never be a substitute for good animal                                                                                                             practices more closely. ❏
health management.                              does not reflect the growing consensus          would have been reasonable for readers
    Prophylactic use of antimicrobials in                                                                                                         * Dr Joel Lexchin is an emergency physician
control programmes should be regularly                                                                                                            in Toronto, Canada, and the Secretary-
assessed for effectiveness and whether                                                                                                            Treasurer of the Medical Lobby for Appropri-
use can be reduced or stopped. Efforts to       importance and benefits of prudent use          Research                                          ate Marketing. He is also a co-author of Drugs
prevent disease should continuously be          principles must be developed and imple-            Stakeholders should identify research          of Choice: A Formulary for General Practice.
in place, aimed at reducing the need for        mented to provide relevant information          priorities to address public health issues
the prophylactic use of antimicrobials.         on antimicrobial resistance for producers       of antimicrobial resistance from anti-            References
                                                and stakeholders. Emphasis must also be         microbial use in farming. Governments,
Education and training                          given to the importance of optimising                                                             1.   Becker MH, Stolley PD, Lasagna L, McEvilla JD, Sloane
                                                                                                universities, research foundations and                 LM. Differential education concerning therapeutics
   Veterinary undergraduate, postgra-           animal health through implementation of         industry should give high priority to                  and resultant physician prescribing patterns. Journal of
duate and continuing education should           disease prevention programmes and good          supporting research in these areas. ❏                  Medical Education 1972;47:118–27.

be evaluated to ensure that preventive          management practices.                                                                             2.   Caudill TS, Johnson MS, Rich EC, McKinney WP. Phy-
                                                                                                                                                       sicians, pharmaceutical sales representatives, and the
medicine, prudent antimicrobial use and             The public should be informed of                                                                   cost of prescribing. Archives of Family Medicine
                                                                                                * Dr Klaus Stöhr is a Scientist at the World
antimicrobial resistance are given high         the human health aspects of antimicro-          Health Organization, Communicable Dis-
                                                                                                                                                       1996;5:201–6.

priority. The effectiveness of this train-      bial use in food animals, so that they can      eases Cluster, Animal and Food-Related            3.   Tomson G, Angunawela I. Patients, doctors and their
                                                                                                                                                       drugs: a study at four levels of health care in an area of
ing should be continuously monitored.           support efforts to control antimicrobial        Public Health Risks, Department of Commu-              Sri Lanka. European Journal of Clinical Pharmacology
   Education strategies emphasising the         resistance.                                     nicable Disease Surveillance and Response.             1990;39:463–7.



Issue No. 28 & 29, 2000
12                                                                                                                                               ESSENTIAL DRUGS MONITOR




  ANTIMICROBIAL                                   RESISTANCE




Antibiotic use and bacterial resistance to
antibiotics in children in a Vietnamese
community                                                                                             Figure 1
                                                                                                      Antibiotic consumption amongst children

                                                                                                                         Symptom(s) of ARI 4 weeks preceding the                         Penicillin 12%
                                                                                                                         study and treated with antibiotics 75%
        n 1999 a household survey was conducted in one agricultural district                                                                                                                         Amoxicillin 11%


   I    in sub-tropical north Viet Nam. This district has 32 community health
        stations, one district hospital, three licensed private pharmacies, a few
        private practitioners, about 16 drug outlets and 362 villages. The re-
                                                                                                        Symptom(s) of ARI 4 weeks
                                                                                                        preceding the study. Not
                                                                                                        treated with antibiotics 7%
                                                                                                                                                                                                           Erythromycin 5%
                                                                                                                                                                                                           Tetracycline 4%
                                                                                                                                                                                                           Other 3%
                                                                                                                   No symptoms/
searchers randomly selected 200 children, aged 1–5 years, within 166                                               Not treated with                                                                       Don’t know 11%
households, from the 225 households in five villages (out of 67 villages where                                     antibiotics 18%
                                                                                                                                                                   Ampicillin 74%
there is a surveillance programme). Nasopharygeal and throat specimens were
collected from each child, and their carers were interviewed to obtain drug use                         Eighty-two percent of the 200 children had symptoms of ARI four weeks preceding the study (left pie chart)
                                                                                                        and seventy-five percent of these children had used antibiotics within this four week period (right pie
information. Researchers explained the purpose of the study to each household                           chart). As some antibiotics were used in combination, the percentages total more than 100%.
and obtained permission to collect the specimens.

    A standardised questionnaire was                  species identification and susceptibility       been treated with antibiotics. On average                    children resistant pathogens were found.
developed, piloted and then used by four              testing.                                        antibiotics were given for 3.9 days and                      Resistance to one or more antibiotics was
experienced local interviewers. They                                                                  ampicillin was the commonest choice;                         shown in 68% (50/74) of H.influenzae
asked questions about the types of anti-              Ignoring treatment                              this is contrary to the national treat-                      isolates, 90% (56/62) of S.pneumoniae
biotics which had been used, how long                                                                 ment guidelines, which recommend                             isolates, and 74% (20/27) of M.catarr-
                                                      guidelines
for, where they were purchased, and                                                                   cotrimoxazole for acute respiratory                          halis isolates. The prior consumption of
what they knew about them. At the same                    It was found that 82% of the children       infection.                                                   ampicillin or pencillin was associated
time, microbiologists from Hanoi Uni-                 had at least one symptom of acute respi-            When deciding which antibiotic to                        with a significantly greater ampicillin
versity collected nasopharygeal (pos-                 ratory infection during the four weeks          use, 67% of carers used a pharmacy, 11%                      or penicillin resistance, odds ratio 2.3
terior nares) and throat (tonsillar) swabs.           prior to interview, and that of these           decided themselves, and 22% followed                         (p<0.05). Multi-drug resistance to a com-
The swabs were immediately placed                     children 91% had been treated with              a doctor’s prescription. The carers were                     bination of trimethoprim/sulphonamide,
in charcoal transport medium, and trans-              antibiotics. Thus, 75% of all the children      asked what drug information they paid                        tetracycline, chloramphenicol, penicillin
ported to the laboratory for culture,                 (both with and without symptoms) had            attention to when treating their children,                   V and ampicillin was found in 26% of
                                                                                                      and replied as below:                                        H.influenzae isolates. Multi-drug resist-
Table 1                                                                                                  daily dosage                            87%               ance was found in 31% of S.pneumoniae
Prevalence of antibiotic resistant (R) and intermediate susceptible (I)                                  how to take the drug                    52%               isolates. Almost all S.pneumoniae isolates
strain of H. influenzae, S. pneumoniae and M. catarrhalis                                                   (e.g. with water)                                      were resistant to both tetracycline and
                                                                                                         total dosage                            12%               trimethoprim/sulphonamide and about
                                 H. influenzae           S. pneumoniae           M. catarrhalis          contraindictions                        8%                half were resistant to chloramphenicol
                                 n = 74                  n = 62                  n = 27                  expiry date                             3%                and/or erythromycin.
                                                                                                         antibiotic resistance                   1 person              The authors conclude that there is
   Antibiotics                   R           I           R           I           R              I
                                                                                                         Eighty percent of the antibiotics were                    a serious public health problem in the
   Ampicillin                    18%         6%          –           –           19%            30%   purchased from small shops and pedlars,                      Vietnamese community. A majority of
   Chloramphenicol               24%         0%          25%         3%          15%            4%    18% from community health stations and                       children will suffer acute respiratory in-
   Ciprofloxacin                 6%          6%          0%          80%         0%             19%   2% from a national hospital pharmacy.                        fection symptoms within any one month.
   Erythromycin                  4%          49%         23%         3%          –              –                                                                  They will be treated inappropriately
   Gentamicin                    0%          2%          3%          95%         0%             0%                                                                 with antibiotics, which are contributing
   Loracarbef                    2%          0%          –           –           0%             4%    A disturbing level                                           to significant levels of resistance. ❏
   Penicillin V                  24%         60%         6%          5%          54%            31%   of resistance
   Tetracycline                  32%         32%         88%         2%          13%            0%
   Trimethoprim/                 44%         3%          32%         12%         59%            19%
                                                                                                          One hundred and sixty-three isolates                     Source: Larsson M, et al. Antibiotic medica-
      Sulphonamide                                                                                    from 145 children were susceptibility                        tion and bacterial resistance to antibiotics: a
   Vancomycin                    –           –           2%          2%          –              –     tested. The carrier rate for S.pneumoniae                    survey of children in a Vietnamese commu-
                                                                                                      was 50%, for H.influenzae 39%, and for                       nity. Tropical Medicine and International
Number of susceptibility tested strains susceptibility tested (n). Antibiotic not tested (–).         M.catarrhalis 17%. In 74% of the 145                         Health 2000;5(20):711–721.




Working to decrease costs
of anti-TB drugs
➢ MARCOS ESPINAL, RAJESH GUPTA,                       to threaten global TB control efforts.          to cure MDR-TB cases.2 In some areas                            To respond to the challenge, WHO and
     MARIO RAVIGLIONE*                                MDR-TB is defined as disease caused by          of the world (especially countries of the                    several partners have launched pilot
                                                      Mycobacterium tuberculosis resistant to         former Soviet Union and eastern Europe),                     projects to manage MDR-TB within pro-
       mong infectious diseases tuber-                at least isoniazid and rifampicin, the two      rates of MDR-TB among new and pre-                           gramme conditions in settings of limited

 A     culosis (TB) remains a leading
       cause of adult mortality.1 Over the
       last decade, the rising spectre of
                                                      most powerful anti-TB drugs. There is
                                                      evidence that short-course chemotherapy
                                                      with first-line anti-TB drugs used to treat
                                                                                                      viously-treated cases are so high that
                                                                                                      they are considered “international
                                                                                                      public health emergencies” given the
                                                                                                                                                                   resources. However, one of the greatest
                                                                                                                                                                   obstacles to providing treatment to
                                                                                                                                                                   patients infected with MDR-TB has been
multidrug-resistant TB (MDR-TB) began                 drug-susceptible cases is not as effective      possibility of international spread.3,4                      the high cost of the second-line anti-TB

                                                                                                                                                                                    Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                          13




  ANTIMICROBIAL                                RESISTANCE


Anti-TB drugs...                                Green Light Committee.7                                                                                                     References
cont’d from pg. 12                              This Committee, housed                                                                                                      1. Raviglione MC, Snider DE
                                                in WHO, is currently com-                                                                                                       Jr, Kochi A. Global epide-
                                                                                                                                                                                miology of tuberculosis.
drugs needed for the management of              prised of six institutions:                                                                                                     Morbidity and mortality
MDR-TB.5 Over the last three years,             Centres for Disease Control                                                                                                     of a worldwide epide-
                                                                                                                                                                                mic. JAMA 1995;273(3):
open market prices for these second-line        and Prevention, Harvard                                                                                                         220–26.
anti-TB drugs have been as high as              Medical School, Médecins
                                                                                                                                                                            2. Espinal MA, et al. Standard
US$15,000 for an 18-month treatment             Sans Frontières, the Na-                                                                                                        short-course chemotherapy
regimen. In contrast, the first-line anti-      tional TB Programme –                                                                                                           for drug-resistant tuberculo-
                                                                                                                                                                                sis: treatment outcome in six
TB drugs needed for management of               Peru, Royal Netherlands                                                                                                         countries. JAMA 2000;283
drug-susceptible TB cost as little as           TB Association and WHO                                                                                                          (19):2537–2545.

US$11 for a six-month treatment regi-           (serving as a permanent                                                                                                     3. WHO, International Union
                                                                                                                                                                                Against Tuberculosis and
men.6 In order to decrease the cost of these    member and secretariat).                                                                                                        Lung Disease. Anti-tuber-
drugs, the WHO Working Group (spe-              Most of the work conducted                                                                                                      culosis drug resistance
cially created to deal with MDR-TB) has                                                                                                                                         in the world: the WHO/
                                                by the Green Light Com-                                                                                                         IUATLD Global Project
negotiated with both the research-based         mittee is performed via                                                                                                         on Anti-tuberculosis Drug
and generic pharmaceutical industry. Ne-        videoconference, telecon-                                                                                                       Resistance Surveillance,
                                                                                                                                                                                Report No. 2. Geneva:
gotiations have resulted in a preferential      ference and e-mail. All                                                                                                         World Health Organiza-
price decrease in the cost of treatment         decisions are made by                                                                                                           tion; 2000. WHO/TB/2000.
                                                                                                                                                                                278.
regimens of up to 90% in comparison to          consensus. 8




                                                                                                                                                                                                                          Photo: WHO/O. Harrer
                                                                                                                                                                            4. Harvard Medical School
the open market price. These preferential           Overall, the process has                                                                                                    and Open Society Institute.
prices were partially achieved through          worked well due to the joint                                                                                                    The global impact of
                                                                                                                                                                                drug-resistant tuberculosis.
global procurement of drugs. Consolidat-        efforts of all institutions                                                                                                     Programme in Infectious
ing the market into a single-demand             involved. Pilot projects                                                                                                        Disease and Social Change.
source not only allowed for some market                                                                                                                                         1999.
                                                have benefited from the
forces to arise, but also for industry mem-     procurement process and         A patient in Tanzania suffering from TB, a disease which is becoming increasingly           5. WHO. Procurement of sec-
                                                                                common and increasingly resistant to drug treatments                                            ond-line anti-tuberculosis
bers to conduct more accurate demand            the negotiations, which, by                                                                                                     drugs for DOTS-Plus Pilot
forecasts that, previously, had been very       virtue of the mechanism                                                                                                         Projects. Proceedings of a
difficult.                                                                                                                                             meeting. Gupta R, Brenner JG, Henry CL, et al, eds.
                                                described, guarantee that high-quality anti-TB drugs provided at preferential prices                   Geneva: World Health Organization; 2000. WHO/CDS/
    At the same time, in order to protect       are used in the best possible, controlled manner. This method of procurement helps to                  TB/2000.276.
against the misuse of drugs and creation        ensure the scientific integrity of the pilot projects and should be explored for use in            6. Khatri. Personal Communication. 2000.
of resistance to these drugs (the last line     other infectious diseases, including HIV/AIDS. ❏                                                   7. WHO. Guidelines for establishing DOTS-Plus Pilot
of chemotherapeutic defence against TB),                                                                                                                        Projects for the management of multi-drug-resistant tu-
these preferentially priced drugs are only                                                                                                                      berculosis. Geneva: World Health Organization; 2000.
                                                                                                                                                                WHO/CDS/TB/2000.279.
released to those projects adhering to          * The authors work for the World Health Organization, Communicable Diseases Cluster, in
                                                                                                                                                           8.   WHO. DOTS-Plus and the Green Light Committee. Ge-
standard scientific guidelines as deter-        Strategy Development and Monitoring for Endemic Bacterial and Viral Diseases, Communi-                          neva: World Health Organization, 2000. WHO/CDS/TB/
mined by an independent body called the         cable Disease Control, Prevention and Eradication.                                                              2000.283.




How Chile tackled overuse
of antimicrobials
         ➢ LUIS BAVESTRELLO                     Table 1
       AND ANGELA  CABELLO*                     Percentage increases in consumption of selected
                                                antibiotics and groups of antibiotics, 1988–1997
         n 1998, the Pan American Infec-

  I      tious Diseases Society and the
         Pan-American Health Organiza-
         tion carried out a study in Chile
                                                   Antimicrobial               1988
                                                                               DDD/1000
                                                                               pop. per day*
                                                                                                  1997
                                                                                                  DDD/1000
                                                                                                  pop. per day
                                                                                                                  Variation
                                                                                                                  % increase

on trends in antimicrobials use during the
previous 10 years.1 The study revealed a           cloxacillin                   0.39               0.417                7
                                                                                                                                                                                                                           Photo: WHO/PAHO/C. Gaggero




significant increase in antibiotic con-            ampicillin                    0.54               0.613               14
sumption, expressed in terms of DDD                amoxicillin                   0.87               5.204             498
(defined daily dose) per 1,000 population          clavul. amoxicillin           0.0025             0.414          16460
per day over the 10 years, based on an-
                                                   cotrimoxazole                 0.965              1.163               20
nual sales data for antibiotics in terms of
                                                   cephalosporins                0.064              0.262             309
both grams consumed and units of sale.2
Noteworthy findings included increases             fluoroquinolones              0.049              0.281             473
in sales of amoxicillin (+ 498%), oral                                                                                             These children playing happily in Chile stand to benefit from the
cephalosporins (+ 309%) and oral fluoro-        * Defined Daily Dose per 1,000 population per day                                  country’s actions to minimise antimicrobial resistance
quinolones (+ 473%) between 1988 and
1997. The only antibiotic with declining        Committee on Health of the National                  individual tablets in Chile’s pharmacies.             displaying posters and by extensive
consumption was chloramphenicol                 Congress. Professional organizations of                                                                    coverage on radio and television news
(-18%). See Tables 1 and 2.                     physicians and chemists, and the National            Hitting the headlines                                 programmes. In addition, the attention
    These findings were submitted to the        Department of Consumer Affairs were                      At the end of September 1999, after               of the pharmaceutical chemists respon-
Chilean Ministry of Health, and meetings        also consulted, with a view to informing             this consultative process, the Ministry               sible for the technical management of
arranged to study what to do about the          the general public before adopting                   of Health acted to control antibiotics, by            pharmacists was drawn to the increase in
problem. Health Ministry staff met with         any potentially unpopular measures.                  making them available only through                    antibiotic consumption over the previous
scientific associations, the body regulat-      This was necessary because people                    chemists and on prescription. Compliance              10 years.
ing drug manufacture and prescribing,           were accustomed to purchasing anti-                  with the measure was encouraged by dis-
the Institute of Public Health and the          biotics without a prescription, and even             tributing leaflets in private chemists,                                         ...cont’d on page 14 ➠


Issue No. 28 & 29, 2000
14                                                                                                                                                    ESSENTIAL DRUGS MONITOR




  ANTIMICROBIAL                                RESISTANCE


Chile... cont’d from pg. 13                      Table 2
                                                 Annual sales of packs of antimicrobials in private pharmacies in Chile, by antimicrobial group, 1988–1997
    Three months after the Ministry’s
action an evaluation study showed a                   Year           Macrolides               Penicillin: broad Penicillin:             Cephalo-       Cotrimox-             Tetra-                Chloram-        Fluoro-
                                                                                              spectrum          M-R Spectrum            sporin         azole                 cycline               phenicol        quinolone
downturn in consumption. This further
study, entitled “Preliminary evaluation of
the impact of the measures to regulate out-           1988              765,800              3,199,000          3,488,600                    .....     1,409,800              836,500              392,600               ....
patient consumption of antimicrobials in              1989              798,400              3,373,700          3,797,800               185,200        1,457,000              851,400              457,100               ....
Chile”, involved a comparison between                 1990              989,235              3,633,271          3,379,425               214,084        1,478,396              870,288              398,428               ....
the same two quarters of two years, one               1991           1,053,390               4,104,949          3,354,194               221,457        1,717,625           1,028,031               402,170               ....
immediately before the introduction of the            1992           1,118,807               4,368,913          3,240,031               247,261        1,578,412              914,297              278,566               ....
measure, the other immediately after. The             1993           1,435,275               5,151,850          3,289,910               322,135        1,752,653              883,301              298,809         240,167
study showed a decline in consumption                 1994           1,400,078               5,090,712          3,250,074               367,539        1,543,922              844,178              276,392         269,452
of 36% in amoxicillin, 56% in ampicillin
                                                      1995           1,615,879               6,213,139          3,548,893               505,036        1,532,223           1,016,890               320,594         307,376
and 30% in erythromycin between the last
                                                      1996           1,818,824               6,858,590          3,676,448               537,154        1,550,226              979,917              341,639         335,728
quarter of 1998 and the same quarter of
1999.                                                 1997           2,076,073               7,799,949          4,035,888               563,902        1,692,889           1,055,055               330,348         414,625
    Expenditure         dropped         by
US$6,483,883 between 1998 and 1999,              … = No data available                                                                                                                Source: International Marketing System
representing a saving for the population
as shown in Table 4.                             the sale and consumption of antibiotics                        Table 4
    Studies reveal that the Ministry of          in Chile. As a result, in Chile antibiotics                    Dollar sales of groups of antimicrobials by private pharmacies in
Health’s control measures introduced             may now only be purchased by prescrip-                         Chile, 1998–1999
after consultation with scientific, profes-      tion. This has reduced self-medication
                                                 and the concomitant threat of microbial                           Group of                                       1998                    1999                Difference(US$)
sional and consumer associations, and
                                                                                                                   antimicrobials
with Parliament, had a clear impact on           resistance.
                                                                                                                   macrolides                             14,763,740                  12,448,627              2,315,113
Table 3                                                                                                            broad spectrum penicillins             13,747,242                  11,227,954              2,519,288
Changes in consumption by DDD/1000 pop./per day between the last                                                   oral cephalosporin                      4,488,543                   4,193,849                294,694
quarter of 1998 and the same quarter of 1999 (immediately after                                                    fluoroquinolone                         4,075,818                   4,115,261                 -39,443
the introduction of the Ministry of Health regulation)                                                             med.-nar. spect. penicillin             4,121,100                   3,275,517                845,583
                                                                                                                   cotrimoxazole                           2,316,260                   1,767,612                548,648
   Antimicrobials             4th quarter 1998         4th quarter 1999              Variation (%)                 Total                                43,512,703                37,028,820                  6,483,883

   clarithromycin               0.366                    0.446                         21.8                     Source: International Marketing System
   azithromycin                 0.342                    0.353                         3.2
   erythromycin                 0.536                    0.370                         -30.9
                                                                                                                    This Chilean example shows that                         Angela Cabello is a pharmaceutical chemist
   amoxicillin                  4.639                    2.943                         -36.5
                                                                                                                given political will, determination, con-                   in the Pharmaceutical Unit, Dr Gustavo Fricke
   ampicillin                   0.391                    0.182                         -53.4                    sultation and public education, effective                   Hospital, Alvarez 1532, Viña del Mar, Chile.
   clavulanic amoxicillin       0.459                    0.443                         -3.5                     measures that save lives – by promoting                     Tel/fax: + 56 32 652450.
   cloxacillin                  0.424                    0.338                         -20.3                    rational use of antibiotics – and money
                                                                                                                                                                            References
   phenoxymethylpenicillin      0.184                    0.111                         -39.7                    are possible. ❏
                                                                                                                                                                            1.   PAHO. Resistencia antimicrobiana en las Américas:
   cotrimoxazol                 0.913                    0.633                         -30.7                                                                                     Magnitud del problema y su contención. Editores
                                                                                                                                                                                 Salavtierra-González R, Benguigui Y. OPS/HCP/HCT/
   tetracycline                 0.499                    0.340                         -31.8                    * Dr Luis Bavestrello is a clinical pharma-                      163/2000 pp.234–240.
                                                                                                                cologist and Head of the Infectious Diseases                2.   Bavestrello L, Cabello A. Estudio del consumo de
   ciprofloxacin                0.317                    0.386                         21.8                                                                                      antimicrobianos en la comunidad. Chile, diez años
                                                                                                                Department, Dr Gustavo Fricke Hospital, and                      después. Rev Chil Infect (1999);16(3):185–190.




Nepal: an economic strategy
to improve prescribing
         pre-post with control study was         fee systems were changed.                                      Table 1

 A       conducted in 33 health facilities
         (10–12 per district) in three dis-
         tricts in Eastern Nepal1. In 1992
                                                     Table 1 shows that both item fees were
                                                 associated with significantly better pre-
                                                 scribing quality than the prescription fee.
                                                                                                                The effects of different kinds of user fee on prescribing quality
                                                                                                                in Nepal

all three districts charged the same flat        The percentage of patients receiving an-                          Fees system            Control flat fee / Px          1-band fee / drug item        2-band fee / drug item
fee per prescription, covering all drugs in      tibiotics decreased and the proportion of                                                        n=12                          n=10                          n=11
whatever amounts. In 1995 the control            prescriptions conforming to standard                              Av. no.                2.9 ➜ 2.9    (0%)              2.9 ➜ 2.0      (-31%)         2.8 ➜ 2.2    (-21%)
district charged the same fee, but the other     treatment guidelines increased in both                            items/Px
two districts had instituted new fee sys-        item fee districts as compared to the pre-
                                                                                                                   % Px with              66.7 ➜ 67.5 (+0.8%)            63.5 ➜ 54.8 (-8.7%)           60.7 ➜ 54.3 (-6.4%)
tems. One district charged a single fee per      scription fee district. The 1-band fee was                        antibiotics
drug item (1-band item fee), whatever            associated with a greater reduction in
the drug, but covering a full course of the      cheap vitamins and tonics, and the 2-band                         % Px with              23.4 ➜ 20.0 (-3.4%)            19.8 ➜ 16.1 (-3.7%)           21.8 ➜ 14.9 (-6.9%)
                                                                                                                   injections
drug. A second district charged a higher         fee with a greater reduction in expensive
fee per expensive item (e.g. antibiotics         injections. ❏                                                     % Px with              27.0 ➜ 22.1 (-4.9%)            26.5 ➜ 8.4     (-18.1%)       23.5 ➜ 15.8 (-7.8%)
and injections) and a lower fee per cheap                                                                          vitamins or tonics
item (e.g. vitamins), each fee covering a                                                                          % Px conforming        23.5 ➜ 26.3 (+2.8%)            31.5 ➜ 45.0 (+13.5%)          31.2 ➜ 47.7 (+16.5%)
                                                 Reference
full course of the drug. All the fees were                                                                         to STGs
                                                 1.   Holloway KA, Gautam BR. The effects of different
priced so as to cost patients about 25% of            charging mechanisms on rational drug use in eastern ru-
                                                                                                                   Av. cost /             24.3 ➜ 33.0 (+35.8%)           27.7 ➜ 28.0 (+1.1%)           25.6 ➜ 24.0 (-6.3%)
average daily household income for two                ral Nepal. Paper presented at the First International
                                                                                                                   Px (NRs)
                                                      Conference on Improving Use of Medicines; 1997 April
drug items. Prescribing was monitored in              1 to 4; Chiang Mai, Thailand. Available on the Web at:
all health facilities before and after the            www.who.int/dap-icium/posters/4e2_Text.html               Px = prescription


                                                                                                                                                                                         Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                        15




  ANTIMICROBIAL                               RESISTANCE




Containing drug resistance
through hospital infection control
         ➢ NIZAM DAMANI*                       suit individual needs.                     catheter-associated and intravenous line       Hospital, 68 Lurgan Road, Portadown, Co.
                                                   Hospitals should have a written dis-   infection is not recommended.                  Armagh BT63 5QQ, Northern Ireland, UK.
        ospitals are a crucial component       infectant policy with procedures to ensure                                                Tel: + 44 128 38 33 4444 ext. 2654, fax:


 H      of the antimicrobial resistance                                                                                                  + 44 128 38 33 4582.
                                               adequate decontamination of equipment      A universal challenge
        problem world wide, because            and the environment. Internationally
        highly vulnerable patients often       recommended sterility checks must be            The control and containment of multi-     References
require prolonged antibiotic therapy, and      carried out on a regular basis. As multi-  resistant micro-organisms represents a
the problem of cross infection arises.                                                    universal challenge requiring national         1. WHO. Recommendations for the control of meticillin-
                                               resistant organisms can survive in the                                                        resistant Staphylococcus aureus (MRSA). Geneva: World
    Every hospital should make con-            environment for prolonged periods, and     and international efforts, as ease of long         Health Organization; 1996. WHO/EMC/LTS/96.1.
tainment and control of multi-resistant        may act as a reservoir for infection, the  distance travel no longer limits spread.
micro-organisms a high priority, and it re-                                                                                              2. The Hospital Infection Control Practices Advisory Com-
                                               hospital environment should be kept        Every hospital should devote ade-
                                                                                                                                             mittee. Recommendations for preventing the spread of
quires a team approach. The first step is      clean, dry and dust free.                  quate resources to an infection control            Vancomycin resistance. Morbidity and Mortality Weekly
to establish an active and effective infec-        Therapeutic devices, such as urinary   programme or health and health care                Report 1995;44:1–13.
tion control committee with responsibility     and intravenous catheters, are not only    resources could suffer. ❏                      3. Global consensus conference on infection control issues
for formulating, implementing and audit-       responsible for the majority of hospital-                                                     related to antimicrobial resistance: Final recommenda-
ing an infection control programme             acquired (nosocomial) bacteraemias, but    * Dr Nizam Damani is Clinical Director and
                                                                                                                                             tions. American Journal of Infection Control 1999;
throughout the hospital.                                                                                                                     27:503–513.
                                               also for cross infection/outbreaks of      Consultant Microbiologist, Craigavon Area
                                               multi-resistant organisms. Urinary                                                                  4. The Hospital Infection Control Practices Ad-
The microbiology                               catheters should be inserted only                                                                        visory Committee. Guidelines for isolation
                                                                                                                                                        precautions in hospitals. American Journal of
laboratory’s role                              when necessary and removed when                                                                          Infection Control 1996;24:24–52.
                                               no longer required. All hygiene
    A good diagnostic microbiology labo-                                                                                                           5. Shlaes DM, Gerding DN, John JF, et al. Soci-
                                               precautions must be followed.
ratory service is essential. Laboratories                                                                                                               ety of Healthcare Epidemiology of America
                                               The use of antibiotics should be                                                                         and Infectious Diseases Society of America
should use internationally recognised
                                               restricted to patients who show                                                                          Joint Committee on the Prevention of Antimi-
protocols to identify organisms and                                                                                                                     crobial Resistance: Guidelines for prevention
                                               clinical signs of infection.
antibiotic sensitivity, and their range of                                                                                                              of antimicrobial resistance in hospitals. Infec-




                                                                                                                                                                                                                        Photo: WHO/PAHO/A. Waak
                                                   The majority of primary blood                                                                        tion Control and Hospital Epidemiology
diagnostic facilities should cover non                                                                                                                  1997;18:279–291.
bacterial and unusual infections. Close        stream infections are associated
liaison with clinicians, the infection         with the use of intravascular de-                                                                   6. Goldman DA, et al. Strategies to prevent and
control team and the drug and therapeu-        vices. Again the best prevention is                                                                      control the emergence and spread of antimi-
                                               to insert an intravascular line only                                                                     crobial-resistant micro-organisms in hospitals.
tics committee is essential. Laboratories                                                                                                               Journal of American Medical Association
should serve as an important source of         if necessary and to keep it in place                                                                     1996; 275:234–240.
local surveillance data both for the           for a minimum period. The rou- No one is more vulnerable to multi-drug resistance than people
hospital and the community.                    tine use of antibiotics to prevent admitted to hospital wards                                                         ■ ■ ■


Antibiotic prescribing:
a crucial element



                                               Changing prescriber behaviour
    Hospital drug and therapeutics
committees should be responsible for
the promotion of rational prescribing,
drug use monitoring and cost con-
tainment. They must regularly review
antibiotic use, conduct audits and give        TRAINING  AND TREATMENT                             of prescriptions conforming to standard              conforming to treatment guidelines) were
doctors feedback to influence prescribing                                                          treatment guidelines) did not improve                much greater than for antibiotic use alone
                                               GUIDELINES IMPROVE
habits. Committees should also approve                                                             when only guidelines were disseminated,              (percentage of prescriptions containing
the use of newer antimicrobial agents,         PRESCRIBING IN UGANDA
                                                                                                   but greatly improved if dissemination was            antibiotics). ❏
which should be restricted to agreed                                                               accompanied by training and supervision.
clinical conditions.                                   randomised controlled trial to test

                                                A
                                                                                                   The intervention used was not only di-
    Doctors must be trained to take re-                the impact of standard treatment                                                                 Reference
                                                                                                   rected at antibiotic prescribing, but other
sponsibility for rational prescribing and              guidelines (STGs) plus training
                                                                                                   aspects of prescribing also. This may                    Kafuko J.M, Zirabumuzaale C, Bagenda D. Rational drug
to justify their antimicrobial use. Their              and supervision on rational pre-                                                                     use in rural health units of Uganda: effect of national
                                                                                                   account for why the changes in prescrib-                 standard treatment guidelines on rational drug use. Final
prescribing policy must be evidence-           scribing was carried out in 127 health
                                                                                                   ing quality (percentage of prescriptions                 report. Kampala: UNICEF, Uganda; 1996.
based and should reflect local antibiotic      units in Uganda. Prescribing was moni-
resistance surveillance data. This can be      tored in all facilities both before and after
achieved by having a written hospital for-     the interventions. In a control group of            Table 1
mulary, and an antibiotic policy that is       42 health units, no intervention was in-            Randomised controlled trial in Uganda
regularly updated and has broad input and      troduced. In a second group of 42 health
consensus among all involved.                  units, the national standard treatment                 Randomised group             n       % prescriptions                   % prescriptions
                                               guidelines were disseminated but no                                                         containing antibiotics            conforming to STG
Infection control measures                     training or supervision was conducted.
                                               In a third group of 29 health units, the               Control group                42      53.0 ➜ 58.0% +5.0%                24.8 ➜ 29.9% +5.1%
   Barrier precautions are vital to pre-       national standard treatment guidelines
vent the spread of multi-resistant micro-      were introduced and on-site training on                Dissemination of STG         42      51.6 ➜ 57.8% +6.2%                24.8 ➜ 32.3% +7.5%
organisms in hospitals. These include          therapeutic problems conducted. In a
isolating patients with multi-resistant        fourth group of 14 health units, the same              STG + on-site training       29      51.7 ➜ 50.7% -1%                  24.0 ➜ 52.0% +28.0%
organisms, and ensuring that staff ad-                                                                in therapeutic problems
                                               was done as for the third group but, in
heres to hand hygiene procedures and           addition, four supervisory visits were                 STG + on-site training       14      54.3 ➜ 54.3% 0%                   21.4 ➜ 55.2% +33.8%
use of appropriate personal protective         conducted over a six-month period.                     in therapeutic problems
equipment. It is important for infection           Table 1 shows how prescribing                      + 4 supervisory visits
control measures to be based on the            changed in the different groups. Prescrib-             in 6 months
local epidemiology and be tailored to          ing quality, (as judged by the percentage

Issue No. 28 & 29, 2000
16                                                                                                                           ESSENTIAL DRUGS MONITOR




  ANTIMICROBIAL                                 RESISTANCE




Prioritising interventions to
contain antimicrobial resistance
                                 ➢ KATHLEEN HOLLOWAY*

        ust as there are many actors and activities that contribute towards anti-

  J     microbial resistance, so there are many potential strategies to contain
        the growth and spread of resistance. The WHO Global Strategy to con-
        tain resistance, (which will be published in 2001 and will be available
on the Web via http://www.who.int/emc/amr), identifies 64 interventions in
total. Of these, 44 interventions are aimed at improving the use of antimicrobial
drugs in humans at the national level or below, (i.e. excluding interventions
concerning animal use, new vaccine and drug development and international
measures).

Critical decisions                               described. The first method was used in




                                                                                                                                                                                              Photo: WHO/PAHO/A.Waak
    No country in the world is imple-            two WHO Regional Offices and one
menting all of these recommended                 country, whilst the Global Strategy was
interventions and most would find it im-         being developed. From the problems en-
possible to do so. Therefore, all countries      countered using the first method, a second
                                                 method was developed and used at WHO
will need to prioritise the interventions
                                                 Headquarters in finalising the present
and choose which ones to implement first
                                                 draft of the Global Strategy.
and which to implement later. Develop-                                                        A pharmacy in Colombia. Ensuring good dispensing practices is seen as a high priority in the
ing countries in particular will need to                                                      fight against antimicrobial resistance
prioritise and choose only those interven-                   REGIONS’
                                                           THE
tions that, in their local contexts, are both       PRIORITISATION PROCESS                    Eastern Mediterranean (EMRO) and the             corner of the chart and were judged to be
feasible and likely to have the greatest                                                      Regional Office for South-East Asia              of highest priority. Those interventions
impact. This article discusses the prob-         Step one: deciding who                       (SEARO), participants were WHO staff             that appeared in the bottom left-hand
lem of how to choose which interventions         participates in the process                  members. In Nepal they were from the             corner of the chart were judged less fea-
will be both feasible and have a signifi-           A list of participants was agreed lo-     Ministry of Health, academic institutions        sible and relevant. For example, in a
cantly large impact. Two methods are             cally. In the Regional Office for the        and local NGOs. All health disciplines           group of 11 people, the maximum score
                                                                                              concerned with antimicrobial use and/or          an intervention could receive for either
Table 1                                                                                       resistance were invited, including all           importance or feasibility was 22 (11 par-
Agreed list of interventions to contain antimicrobial resistance                              those concerned with communicable dis-           ticipants awarding a maximum of two
                                                                                              eases, health systems, essential drugs and       points). The points plotted on the matrix
   Target group           Recommended interventions                                           primary health care.                             would therefore be 22 for importance and
                                                                                                                                               22 for feasibility.
   A                      1.   Education on appropriate use                                   Step two: developing a list
   Patients and           2.   Education on hygiene                                           of interventions                                 Diverse views
   the public             3.   Discourage self-medication                                         EMRO participants developed a list               The graphs below (figures 1–3) in-
                                                                                              of interventions starting from those             dicate the priority given to different
   B                      1.   Training                                                       recommended in the WHO draft Global
   Prescribers and        2.   Guidelines and formularies                                                                                      interventions. Comparison shows how the
                                                                                              Strategy. SEARO and Nepali parti-
   dispensers             3.   Monitoring and supervision                                                                                      various regions agreed and disagreed on
                                                                                              cipants also agreed to use this list (see
                          4.   Regulation of professionals                                                                                     which interventions should have highest
                          5.   Educate prescribers about promotion
                                                                                              Table 1).
                                                                                                                                               priority. The reasons for differences in the
                                                                                              Step three: voting on the                        priorities between these three groups may
   C                      1.   Therapeutic committees                                                                                          have been due to different priorities in
   Health systems         2.   Infection control committees                                   proposed interventions
                                                                                                                                               different areas, but were also in large part
                          3.   Guidelines for antimicrobial use                                   Each intervention was scored accord-
                                                                                                                                               due to the different expertise of partici-
                          4.   Antimicrobial use surveillance                                 ing to:
                          5.   Laboratory network and epidemiological                                                                          pants in the different groups. For example,
                                  resistance surveillance
                                                                                              (1) the importance or relevance of any           in SEARO there was no one specialising
                                                                                                  impact it might have, and                    in health systems or drug regulation, in
   D                      1.  National AMR task force with budget                             (2) the feasibility of implementation.           Nepal microbiologists were poorly rep-
   Government             2.  Drug policies e.g. essential drugs list, standard                   It was agreed that “relevance” would         resented, as were agriculturalists in both
   policies, strategies         treatment guidelines                                          take into account whether an intervention        EMRO and SEARO.
   and regulations        3. Registration of all drug outlets                                 would impact on the diseases of particu-
                          4. Antimicrobials by prescription-only                                                                               The most feasible and important inter-
                                                                                              lar concern locally, and that “feasibility”
                          5. Dispensing of antimiocrobials by licensed staff only
                                                                                              would take into consideration both cost          ventions agreed by everyone included:
                          6. Quality assurance system
                          7. Drug licensing to include resistance data                        of implementation and the political con-
                                                                                                                                               ➤ training of prescribers and dispensers,
                          8. Undergraduate and postgraduate training on AMR                   text. The scoring was as follows:
                                                                                                                                                 and the use of guidelines and formu-
                          9. Access to evidence-based drug information                            0 = not feasible or no relevant impact         laries;
                          10. Cut perverse rational drug use economic incentives                  1 = medium feasibility or medium
                          11. Monitor and supervise drug promotion                                     relevant effect                         ➤ establishing infection control commit-
                          12. Monitor and link AMR and drug use data                                                                             tees, guidelines for antimicrobial use,
                                                                                                  2 = good feasibility or very relevant
                                                                                                       effect                                    and surveillance of antimicrobial use
   E                      1.   Incentives for industry to do research and development                                                            in hospitals;
   Pharmaceutical         2.   Monitor and supervise drug promotion                           Step four: collating the voting data
   industry               3.   Production according to Good Manufacturing                                                                      ➤ developing national drug policies,
                                 Practice standards                                               All the participants’ scores for likely
                                                                                                                                                 essential drugs lists and standard
                                                                                              relevant impact and feasibility for each
                                                                                                                                                 treatment guidelines;
   F                      1.   Surveillance of resistance and use                             intervention were added up and then plot-
   Non-human              2.   Phase-out growth promoters                                     ted on a matrix. Interventions that were         ➤ ensuring undergraduate and post-
   antimicrobial use      3.   Educate farmers and vets                                       likely to have the greatest impact and be          graduate training on antimicrobial
                                                                                              feasible appeared in the top right-hand            resistance;

                                                                                                                                                         Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                                                                                  17




  ANTIMICROBIAL                               RESISTANCE


➤ ensuring drugs are produced accord-          clinical microbiology and other related       ➤ the interrelationship between various                                                                          low, and consideration was given to
  ing to Good Manufacturing Practice           disciplines from all over the world were        interventions, including the need to                                                                           whether the ranking would vary accord-
  standards.                                   invited to a workshop in Geneva. Parti-         undertake some interventions in a                                                                              ing to a national health system’s level of
The least feasible and important inter-        cipants were divided into three working         logical sequence.                                                                                              development.
ventions agreed by everyone included:          groups, with each considering inter-              As a result of this process, interven-                                                                          Once interventions for each target
                                               ventions aimed at a particular target         tions were ranked as high, medium and                                                                                                                          ...cont’d on page 18 ➠
➤ ensuring that antimicrobials are dis-        audience:
  pensed by licensed staff and only with
  a prescription;                                 Group 1: Prescribers and dispensers
                                                                                             Figure 1
                                                  Group 2: Hospitals
➤ cutting perverse economic incentives                                                       Prioritisation of interventions by the 11 members
  to prescribe antibiotics – for example          Group 3: Health systems                    of EMRO antimicrobial resistance task force
  the problem of dispensing prescribers            For each target audience, the interven-
  earning more money from selling              tions were prioritised according to their                   25
  antibiotics than from other drugs;           relative merits and ranked according to
                                                                                                                                                                                                                                         8                      Feasible and relevant
➤ monitoring and linking data concern-         sequence and importance of implemen-                                                                          4                    6                                        3             2             1
  ing antimicrobial resistance and             tation. This complex task required                          20                                                4            5                3 3                 5           1                      3
                                                                                                                                                                          3                2 1
  antimicrobial use;                           consideration of multiple factors relating                                     11                             12                            9 4 3
                                               to each intervention including:                                                                                                                        1                    2                      2
                                                                                                                                            2                1                    5
➤ monitoring and supervising drug pro-                                                                     15                                       1                             7
                                               ➤ overall importance of the interven-



                                                                                              Importance
  motion both for human and animal
  use;                                           tion to improving the appropriate use                                                                                            2
                                                 of antimicrobials and containing                          10               10
➤ phasing out growth promoters in                antimicrobial resistance;                                                                                                                        A       interventions targeting patients, families, communities
  animal use.                                                                                                                                                                                     B       interventions targeting prescribers and dispensers
                                               ➤ likely impact, allowing for the ex-                                                                                                              C       interventions targeting health systems
                                                 pected cost of implementation;                               5           Not feasible or relevant                                                D       interventions involving government policies, strategies, regulations
           PRIORITISING                                                                                                                                                                           E       interventions targeting the pharmaceutical industry
                                                                                                                                                                                                          interventions targeting non-human antimicrobial use
 INTERVENTIONS FOR THE
                                               ➤ complexity of implementation, con-                                                                                                               F
                                                                                                              0
                                                 sidering the capacity of various health
 WHO GLOBAL STRATEGY                             care systems and political realities;
                                                                                                                   0                  5                                           10
                                                                                                                                                                                             Feasibility
                                                                                                                                                                                                                        15                                      20                  25

    As a result of the diverse views ob-
                                               ➤ time required for implementation
tained from the regions, a different
                                                 and the expected lag period before          Figure 2
process of prioritisation was conducted
for the draft Global Strategy, in order to
                                                 outcomes could be expected;                 Prioritisation of interventions by 15 health officials in Nepal
produce some concrete practical advice         ➤ the accuracy with which most health
for Member States.                               care systems could assess the efficacy                                                                                                                       3        4
    Experts in the fields of drug use,           of each intervention;                                        25                                                              2        3                               1       2         3                  3    1 1
                                                                                                                                                        5                                                              5
                                                                                                                                                                                       1           3 11 13                                        2
                                                                                                                                                4                                                                      4 3 2                  8
                                                                                                                                                              1                        5     1        6                            9
                                                                                                              20
            Priorities in the WHO Global Strategy                                                                                               10           12
                                                                                                                                                              2
                                                                                                                                                                                                                  2
                                                                                                 Importance




                                                                                                                                                                                                                            Feasible and relevant
        for Containment of Antimicrobial Resistance                                                                                                               7


  Although all interventions were classi-      ◆ disease prevention (including                                15
  fied into fundamental, high, medium            immunization) and infection control                                                                                                                          A       interventions targeting patients, families, communities
  and low, only the first two categories         issues.                                                                                                                                                      B       interventions targeting prescribers and dispensers
                                                                                                                                 Not feasible or relevant                                                     C       interventions targeting health systems
  are shown below. Within the two                                                                                                                                                                                     interventions involving government policies, strategies, regulations
                                               3. Targeted undergraduate and post-                                                                                                                            D
  priority groupings shown here,                                                                                                                                                                              E       interventions targeting the pharmaceutical industry
                                                  graduate education programmes
  interventions are not ranked.                                                                                                                                                                               F       interventions targeting non-human antimicrobial use
                                                  for all prescribers, dispensers and                         0
  Fundamental interventions                       other health care workers, and                                      0                                 10                                          15                                       20                          25
  Make containment of antimicrobial               veterinarians, on accurate diagnosis                                                                                                           Feasibility
  resistance a national priority                  and management of common
  including:                                      infections.
                                                                                             Figure 3
  ◆ creating a national task force;            4. Development, updating and use of
                                                  standard treatment guidelines and
                                                                                             Prioritisation of interventions by 7 staff members of SEARO
  ◆ allocating resources to implement
     interventions to contain antimicrobial       treatment algorithms to foster
                                                  appropriate use of antimicrobials.                        15
     resistance;                                                                                                                                                                                                            1
                                                                                                                                                                                       1                                   1 4           3                                    3 8
  ◆ developing indicators to monitor           5. Infection control programmes with
                                                                                                                                                                                       1          3           3 2              1                      2 2            5
     and evaluate the impact of an                responsibility for effective manage-
                                                                                                                                                                  3 4             3 4             2                                                                            2
     antimicrobial resistance strategy;           ment of antimicrobial resistance in
                                                                                                                                                    2                 5               12          9               6
  ◆ designating or developing reference           hospitals.
                                                                                                            10                         10
     microbiology laboratory facilities.       6. Diagnostic laboratories that provide:                                                                               7                                                                Feasible and relevant
     These would coordinate effective,
                                                                                               Importance




                                               ◆ microbiology laboratory services                                                                   5                 1
     epidemiologically-sound, surveillance
                                                  which are appropriately matched                                                                                 11
     of antimicrobial resistance among
                                                  to the level of the hospital (e.g.
     common pathogens in the community,                                                                       5
                                                  secondary, tertiary);                                                                                                                                   A        interventions targeting patients, families, communities
     hospitals and other health care
                                               ◆ appropriate diagnostic tests, bacte-                                                                                                                     B        interventions targeting prescribers and dispensers
     facilities.                                                                                                                 Not feasible or relevant                                                 C        interventions targeting health systems
                                                  rial identification, antimicrobial                                                                                                                      D        interventions involving government policies, strategies, regulations
  High priority interventions                     susceptibility tests of key pathogens,                                                                                                                  E        interventions targeting the pharmaceutical industry
                                                  with adequate quality assurance,                                                                                                                        F        interventions targeting non-human antimicrobial use
  1. Patient education on:
                                                  and timely, relevant reporting of                           0
  ◆ the importance of measures to                 results.                                                        0                                                   5                                                                  10                                              15
     prevent infection such as immuniza-                                                                                                                                                     Feasibility
     tion, vector control, use of bed-nets;    7. Limiting the availability of
  ◆ simple measures that may reduce               antimicrobials to prescription-only
                                                                                             The figures should be viewed in conjunction with Table 1, as the different shapes and colours on the
     transmission of infection in the             status, except in special circum-
                                                                                             three graphs each represent one of the six target groups (A–F) listed in the Table. For example, a
     household and community, such as             stances where they may be                  green circle signifies D – interventions involving government policies, strategies and regulations.
     hand washing, food hygiene.                  dispensed on the advice of a               The numbers within each shape correspond to the different recommended interventions in each of
                                                  trained health care professional.          the target groups. So there are 12 green circles on the map numbered 1 to 12, corresponding to the
  2. Prescriber and dispenser (including
                                               8. Ensuring that only antimicrobials          numbered list of interventions under D in Table 1. Their position on the graph is dependent on the
     drug seller) education on:
                                                                                             scores participants awarded them. For example, D10 – cutting perverse rational drug use economic
  ◆ the importance of appropriate                 meeting international standards of
                                                                                             incentives – appears in the bottom left-hand corner of the graph, showing that it received the lowest
     antimicrobial use and containment            quality, safety and efficacy are           scores for both importance and feasibility.
     of antimicrobial resistance;                 granted marketing authorisation.
                                                                                             The dotted green cross lines signify where the average score (1 point for both importance and
                                                                                             feasibility awarded by each person in the group) would appear.


Issue No. 28 & 29, 2000
18                                                                                                                                   ESSENTIAL DRUGS MONITOR




  ANTIMICROBIAL                                 RESISTANCE


Prioritising interventions...                            INTERVENTIONSFOR                                Interestingly, regional staff felt that
cont’d from pg. 17                                         MAXIMUM IMPACT                            surveillance of antimicrobial use in hos-
                                                                                                     pitals was feasible and important, and
audience were ranked, the interventions                Comparison of the priorities identified       gave it higher priority than the experts
were then ranked according to their over-          at country, regional and international            invited to Geneva did. On the other hand,
all importance and timing (sequence) of            levels shows many similarities. The in-           while the Geneva group felt that restrict-
implementation, without consideration of           terventions agreed by everyone to be both         ing antimicrobials to prescription-only
their target audience. This was done by            high priority and feasible are:                   status was very important, regional staff
all the participants in a plenary session          1. training prescribers and dispensers,           felt that it was not feasible.
(see box). It was recognised that some                and using guidelines and formularies;              There is no hard evidence as to which
priorities might vary depending on the             2. establishing infection control commit-         interventions are most important and have
health care system in which they would                tees and guidelines for antimicrobial          the greatest impact, and expert opinion
be implemented. However, this did not                 use;                                           varies. Nevertheless the two different
impact to any significant extent on the                                                              processes of prioritisation identified the
                                                   3. developing national drug policies,             five interventions listed above. Everyone
priority given to the majority of very high
                                                      essential drugs lists and standard treat-      agreed that these interventions were fea-
priority interventions.
                                                      ment guidelines;




                                                                                                                                                                                                            Department of Health, UK
    Although it was not planned to address                                                           sible and would have the greatest impact
issues relating to consumers and drug              4. ensuring undergraduate and post-               on antimicrobial resistance if adequately
promotion at this workshop, in fact they              graduate training on antimicrobial             implemented. ❏
were also considered. This was because                resistance;
participants, particularly in Group 1,             5. ensuring that drugs are produced ac-           * Dr Kathleen Holloway is a Medical Of-
felt that prescribers and dispensers                  cording to good manufacturing                  ficer in the Department of Essential Drugs        A leaflet from the UK’s public education
could not be considered separately from               practice standards and are of adequate         and Medicines Policy at the World Health          campaign on the correct use of antibiotics
consumers.                                            quality.                                       Organization.




Useful websites on antimicrobial resistance
APUA-Alliance for the Prudent Use of Antibiotics                  US National Center for Infectious Diseases                         WHO. Integrated management of childhood illnesses: A WHO/
http://www.antibiotic.org (see also EDM No.24 p.20)               http://www.cdc.gov/ncidod/eidtopics.htm                            UNICEF initiative. WHO Bulletin 1997;75 (Supplement 1).

AR InfoBank-WHO Antimicrobial Resistance Information Bank         Washington University Infectious Disease Division, USA             WHO. The medical impact of the use of antimicrobials in food
http://oms2.b3e.jussieu.fr/arinfobank                             http://www.id.wustl.edu/                                           animals: Report and proceedings of a WHO meeting, Berlin,
                                                                                                                                     Germany, 13–17 October 1997. Geneva: World Health
BUBL Catalogue of Internet Resources – Infectious Diseases        WHO Communicable Diseases Home Page
                                                                                                                                     Organization; 1997. WHO/EMC/ZOO/97.4.
http://bubl.ac.uk/link/i/infectiousdiseases.htm                   http://www.who.int/health-topics/idindex.htm
                                                                                                                                     WHO. Treatment of tuberculosis: guidelines for national
Center for Adaptation Genetics and Drug Resistance                WHO/TDR (Special Programme for Tropical Disease
                                                                  and Research)                                                      programmes; 2nd ed. Geneva: World Health Organization;
http://www.healthsci.tufts.edu/labs/Sblevy/home.html                                                                                 1997. WHO/TB/97.220.
                                                                  http://www.who.int/tdr
Center for Complex Infectious Diseases                                                                                               WHO. Use of quinolones in food animals and potential impact
http://www.ccid.org/                                              Selected references                                                on human health. Report and proceedings of a WHO meeting,
                                                                                                                                     Geneva, Switzerland, 2–5 June 1998. Geneva: World Health
Centers for Disease Control, Drug Resistance Homepage             Coast J, Smith RD, Millar MR. An economic perspective on           Organization; 1998. WHO/EMC/ZDI/98.12.
http://www.cdc.gov/drugresistance/                                policy to reduce antimicrobial resistance. Soc Sci Med
                                                                  1998;46:29–38.                                                     WHO. Basis for the development of an evidence-based
CIA. The global infectious disease threat and its implications                                                                       case-management strategy for MDR-TB within the WHO’s
for the United States. 1999                                       Fidler DP. Legal issues associated with antimicrobial drug         DOTS Strategy. Geneva: World Health Organization; 1999.
http://www.odci.gov/cia/publications/nie/report/nie99-17d.html    resistance. Emerg Infect Dis 1998;4:169–77.                        WHO/TB/99.269.
EARSS-European antimicrobial resistance surveillance system       Finch RG, Williams RJ. Eds. Antibiotic resistance. Clin Infect
                                                                                                                                     WHO. Containing antimicrobial resistance. Review of the
http://EARSS.rivm.nl                                              Dis 1999;5(2).                                                     literature and report of a WHO workshop on the development of
                                                                  Goldmann DA, Huskins WC. Control of nosocomial anti-               a global strategy for the containment of antimicrobial resistance.
Eurosurveillance                                                                                                                     Geneva, Switzerland, 4–5 February 1999. Geneva: World
http://eurosurv.org/                                              microbial-resistant bacteria: a strategic priority for hospitals
                                                                  worldwide. Clin Infect Dis 1997;24 (Supplement 1):S139–45.         Health Organization; 1999. WHO/CDS/CSR/DRS/99.2.
                                                                                                                                     www.who.int/emc/WHO_docs/general.htm
Global Polio Eradication Initiative
http://www.polioeradication.org                                   Hart CA, Kariuki S. Antimicrobial resistance in developing
                                                                  countries. BMJ 1998;317:647–650.                                   WHO. WHO report on infectious diseases. Removing obstacles
                                                                                                                                     to healthy development. Geneva: World Health Organization;
Infectious Disease News                                           Institute of Medicine. Antimicrobial resistance: issues and
http://www.slackinc.com/general/idn/idnhome.htm                                                                                      1999. WHO/CDS/99.1.
                                                                  options. Workshop report. Washington D.C.: National Academy        http://www.who.int/infectious-disease-report/
                                                                  Press; 1998. http://books.nap.edu/books/0309060842/html/
International Society for Infectious Diseases
http://isid.organize-it.com/                                      R1.html#pagetop                                                    WHO. Anti-tuberculosis drug resistance in the world. Report
                                                                                                                                     no. 2. Prevalence and trends. The WHO/International Union
                                                                  Pittet D et al. Effectiveness of a hospital-wide programme to      Against Tuberculosis and Lung Disease global report on anti-
Johns Hopkins University – Infectious Diseases                    improve compliance with hand hygiene. Lancet 2000;356:
http://www.hopkins-id.edu/index_id_links.html                                                                                        tuberculosis drug resistance surveillance. Geneva: World Health
                                                                  1307–1312.                                                         Organization; 2000. WHO/CDS/TB/2000.278.
Karolinska Institute, Sweden                                      Polk HC Jr, Christmas AB. Prophylactic antibiotics in surgery
http://micf.mic.ki.se/Diseases/                                                                                                      WHO. Global tuberculosis control: WHO Report 2000. Geneva:
                                                                  and surgical wound infections. Am Surg 2000;66:105–11.
                                                                                                                                     World Health Organization; 2000. WHO/CDS/TB/2000.275.
National Foundation for Infectious Diseases, USA                  UK Standing Medical Advisory Committee Sub-Group on
http://www.nfid.org/                                                                                                                 WHO. Guidelines for establishing DOTS-Plus pilot projects for
                                                                  Antimicrobial Resistance. The path of least resistance. London:
                                                                  Department of Health; 1998.                                        the management of multidrug-resistant tuberculosis (MDR-TB).
Project Icare: Intensive Care Antimicrobial Resistance                                                                               Geneva: World Health Organization; 2000. WHO/CDS/TB/
                                                                  http://www.open.gov.uk/doh/smac.htm
Epidemiology                                                                                                                         2000.279.
http://www.sph.emory.edu/ICARE/                                   WHO. World Health Assembly 1998. Emerging and other
                                                                  communicable diseases: antimicrobial resistance. WHA51.17,         WHO. Management of the child with a serious infection or
Roll Back Malaria                                                 agenda item 21.3.                                                  severe malnutrition: guidelines for care at the first-referral level
http://www.rbm.who.int/                                           http://www.who.int/emc/                                            in developing countries. Geneva: World Health Organization;
                                                                                                                                     2000. WHO/FCH/00.1.
Stop TB Initiative                                                WHO. Anti-tuberculosis drug resistance in the world. The
http://www.stoptb.org                                             WHO/International Union Against Tuberculosis and Lung              WHO. World Health Organization report on infectious diseases
                                                                  Disease global report on anti-tuberculosis drug resistance         2000. Overcoming antimicrobial resistance. Geneva: World
The Hot Zone: Emerging Infectious Diseases Reports                surveillance 1994–97. Geneva: World Health Organization;           Health Organization; 2000. WHO/CDS/2000.2.
and Web Sites                                                     1997. WHO/TB/97.229.                                               http://www.who.int/infectious-disease-report-2000
http://www.qis.net/~edwardmc/eid.htm
                                                                  WHO. Guidelines for the management of drug-resistant               WHO. Surveillance standards for antimicrobial resistance.
UK Public Health Laboratory                                       tuberculosis. Geneva: World Health Organization; 1997. WHO/        Geneva: World Health Organization; 2000. CDS/CSR/DRS
http://www.phls.co.uk/                                            TB/96.210.                                                         2000.2 (in preparation).


                                                                                                                                                                  Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                  19




  ANTIMICROBIAL                                RESISTANCE




Pioneers of
antimicrobial resistance
Paul Ehrlich, 1854–1915                                         Selman Waksman, 1888–1973                                         Robert Koch, 1843–1910
                   A German medical scientist renowned                            A Ukrainian-born biochemist, Selman                              A 1905 Nobel Prize honoree, Koch was
                   for his pioneering work in haematol-                           Waksman played a major role in initi-                            the first scientist to identify the organ-
                   ogy, immunology and chemotherapy,                              ating a calculated, systematic search for                        ism that causes tuberculosis, Koch is
                   Ehrlich won the 1908 Nobel Prize for                           antibiotics among microbes. His dis-                             considered the founder of modern
                   his discovery of the first effective                           covery of streptomycin – effective in                            bacteriology because he successfully
                   treatment for syphilis. As well as his                         the treatment of tuberculosis – garnered                         isolated several disease-causing bacte-
                   research into early chemotherapy,                              him the Nobel Prize in 1952.                                     ria and discovered the animal vectors
                   Ehrlich also developed “side chain                                                                                              of a number of major diseases includ-
theory” a hypothesis that provided the first plausible                                                                            ing anthrax. Through his many experiments, Koch
description of the body’s own immunological response            Sir Alexander Fleming, 1881–1955                                  discovered how to obtain microorganisms from animals,
                                                                                                                                  and how to culture those same samples. It was Koch
to destructive pathogens.
                                                                                 Honoured with a Nobel Prize for his              who discovered that cholera is primarily a water-borne
                                                                                 discovery of penicillin, Fleming                 disease.
                                                                                 transformed medical science with
Louis Pasteur, 1822–1895
                                                                                 the development of the world’s first
                  Considered one of the greatest French                          antibiotic. While working with Sta-              John Enders, 1897–1985
                  biologists of the nineteenth century,                          phylococcus bacteria in 1928, the
                                                                                                                                                    American microbiologist and Nobel
                  Pasteur devoted his life to solving                            Scottish bacteriologist noticed a                                  laureate John Enders led a research
                  practical problems in industry, agri-                          bacteria-free circle around a mould                                team which developed a technique for
                  culture and medicine. Pasteur was             growth contaminating a culture of staphylococci. Upon                               growing viruses in cultured cells. He
                  the first to discover that fermentation       further investigation he discovered a substance that                                showed that poliomyelitis viruses grew
                  and putrefaction only took place in the       prevented bacterial replication even when diluted                                   in both brain and cultured tissues and
                  presence of living organisms. With            800 times. In 1943 he was elected fellow of the Royal                               in this way caused cell destruction.
further research he developed the technique of pasteuri-        Society and knighted in 1944.                                     John Enders went on to demonstrate the safety of cul-
zation that not only revolutionized the dairy industry,                                                                           tured viruses in producing immunity, and proved that
but food processing as well.                                                           ◆       ◆    ◆                             measles could be prevented through vaccination.




  LETTERS               TO      THE            EDITOR


Private sector prescribing                      offices is impractical, and often impossi-         Substandard chloroquine                        acceptable level is between 118.75 and
                                                ble to implement. Here in Tanzania’s               in Ghana                                       131.25 per 5ml.
Editor,                                         Dodoma region the Out Patient Service                                                                 Of the 38 tablet samples analysed, four
    When I worked as a pharmacist in the        has adopted my suggestion of patients              Editor,                                        contained levels of chloroquine phosphate
public sector I found it relatively easy to     keeping a “health booklet”. The booklet                                                           below the minimum requirement, with
                                                                                                       Countries in tropical Africa account
promote rational use of drugs through           is in fact a primary school exercise book,                                                        one sample at 38.9%. Of the 57 samples
                                                                                                   for more than 90% of total malaria inci-
adherence to the essential drugs list,          widely available and priced at around                                                             of syrup 10 contained levels of active in-
                                                                                                   dence and the great majority of malaria
standard treatment guidelines and formu-        US$0.06. As the booklet is the patient’s                                                          gredient below the minimum required.
                                                                                                   deaths, with children the most vulnerable
laries. However, now employed in the            property, a sense of ownership means it                                                               We conclude that during the eight-year
                                                is usually well kept and made available            to the disease. Cloroquine is one of the
private sector, I find these tools difficult                                                                                                      study period some malaria sufferers were
                                                whenever requested.                                most frequently used drugs in prevention       exposed to significant amounts of sub-
to use because of prescribers’ resistance                                                          and treatment. But in recent years in some
to what they see as restrictions upon them.         The system’s advantages are that it can                                                       standard chloroquine phosphate in both
                                                provide a full patient history, particularly       endemic areas certain strains of plasmo-       tablets and syrups. However, lessons have
    Obviously the forces driving the pri-                                                          dium falciparum, one of the parasites
vate sector are unlike those in the public      useful in cases such as hypertension, dia-                                                        been learned, and steps taken to improve
                                                betes, asthma or allergy. Also data are            responsible for malaria, has become re-        matters. One local manufacturer had to
sector. For example, cost containment is                                                           sistant to chloroquine. Among the reasons
not a priority, as the consumer (generally      recorded chronologically, whereas before                                                          withdraw affected batches of drugs and
                                                we often had to sort through numerous              cited for this is the manufacture, sale and    had his factory closed until an effective
those dissatisfied with the public health                                                          use of substandard chloroquine formula-
care system) pays for services, mainly          pieces of paper and put them in date or-                                                          quality assurance scheme was in place.
                                                der. When there is a shortage of hospital          tions. In Ghana we have completed an           Local manufacturers supplying the Min-
through some form of health insurance.                                                             eight-year study to discover the scale of
My question is, in the private sector is it     cards and files, the booklet can also be                                                          istry of Health must now have their
                                                used as an in patient file or as a growth          the problem, and it has reinforced con-        products tested and certified by the na-
really possible to rationalise medicines’                                                          cerns about the quality of chloroquine
use and still have a good income? I would       chart for the under-fives. As senior doc-                                                         tional quality control laboratory. The
                                                tors can comment on and change previous            available here.                                Food and Drugs Board is implementing
be interested to hear readers’ views.                                                                  Thirty-eight samples of chloroquine
                                                diagnoses and treatments, the system can                                                          measures to assure drug quality in manu-
                                                help in improving junior colleagues’ skills        phosphate tablets and 57 samples of syr-       facture, supply and distribution. And
—Dr Atieno Ojoo, P.O. Box 13576, Nairobi,
                                                and prescribing practices.                         ups, manufactured locally by different         during 1999 an association of drug manu-
Kenya.
                                                    Lack of supplies and of motivated staff        firms, were tested in the Ghana Standards      facturers was formed, pledging to comply
                                                should convince hospital managements to            Board’s laboratories between 1992 and          with WHO Good Manufacturing
             ✍      ✍      ✍                    rely more on user commitment, and let              1999. All the samples were analysed ac-        Practices.
                                                patients document their own medical                cording to British Pharmacopoiea assay
A simple solution to outpatient                 histories.                                         methods. The Pharmacopoiea’s specifi-          —Charlotte Ohene-Manu and Jonathan
record keeping?                                                                                    cation for the content of chloroquine          Martey, Ghana Standards Board, Drugs
                                                —Dr Massimo Serventi, Paediatrician,
                                                                                                   phosphate in tablets ranges between            and Cosmetics Department, P.O. Box MB,
Editor,                                         Dodoma General Hospital, Box 1498,
                                                                                                   92.5% and 107% of the label claim. In          245, Accra, Ghana.
                                                Dodoma, Tanzania.
   In developing countries the idea of                                                             Ghanaian produced tablets 250 mg of
keeping medical records in hospital                          ✍      ✍      ✍                       chloroquine is the norm and for syrup the                   ✍      ✍     ✍

Issue No. 28 & 29, 2000
                             20                                                                                                                              ESSENTIAL DRUGS MONITOR




                               NATIONAL                     DRUG            POLICY




                             Meetings give impetus to Africa’s
                             essential drugs programmes
                                     ssential drugs programme manag-          that local industries should not be put at       and efficiency.                               inspection services; and the legislation

                               E     ers in Africa have met to debate a
                                     range of pharmaceutical issues
                                     and move forward their agenda to
                                                                              an undue disadvantage in the bidding
                                                                              process.
                                                                                  Delegates emphasised that easy access
                                                                                                                                   Rational use of drugs was high on the
                                                                                                                               agenda. Participants recommended
                                                                                                                               that Member States develop strategies
                                                                                                                                                                             and regulations necessary to ensure drug
                                                                                                                                                                             quality. As in South Africa there was
                                                                                                                                                                             much discussion on improved pricing
                             ensure access to essential medicines. At         to reliable information on pharmaceu-            and incorporate rational use principles in    policy. Participants called for com-
                             two critical meetings they endorsed the          tical suppliers and pricing was vital to         health workers’ training curricula. Phar-     plementarity between the public and
                             Intensified Essential Drugs Programme            achieve optimal quality at affordable            macotherapeutics committees were seen         private sectors, the creation of autono-
                             for the African Region, and made                 prices. A Web site should be established,        as a way to improve rational use by pre-      mous central medical stores, promotion
                             numerous policy recommendations.                 coordinated by WHO, to make such in-             scribers and dispensers, and should be        of local production, and state and com-
                                 The first meeting, in South Africa in        formation freely available and keep it           introduced at all levels of care.             munity co-financing to improve drug
                             March 2000, brought together managers            updated.                                             Acknowledging the role of traditional     supply and access. They also discussed
                             from 16 anglophone countries. They                   Participants also wanted information         medicines in African health care, pro-        integrating drug policy programmes in
                             called on health authorities to adopt            disseminated on the concept and benefits         gramme managers urged WHO to                  health development plans, creating ra-
                             good procurement practices for essential         of harmonisation of drug                                        give support to countries      tional drug use strategies, and improving
                             drugs. Authorities should capitalise             regulatory activities, and                                      in deciding how best to        staff training.
                             on economies of scale, and make pricing          the promotion of common                                         use them within health             At both meetings WHO requested
                             information available to prescribers,            minimum standards. This                                         systems.                       countries to specify the activities they
                             dispensers, consumers and health insur-          would generate confi-                                               In August 2000 it was      would carry out to implement the Inten-
                             ance companies, to enable them to make           dence in the quality of                                         the turn of 38 essential       sified Essential Drugs Programme, so that
                             informed decisions. Participants also pro-       services. Public health                                         drugs programme manag-         the Organization can make detailed plans
                             posed that governments should encourage          needs rather than commer-                                       ers from 20 francophone        for supporting them. But important work
                             local production of essential drugs, and         cial interests should drive                                     countries to spend time        is already underway. The WHO Regional
                             remove taxes on both the drugs and their         the harmonisation pro-                                          reflecting on their work       Office for Africa is running training in
                             raw materials.                                   cess, delegates stressed. In                                    and planning ahead. Meet-      good manufacturing practices, and the
                                 The managers endorsed the idea of            addition, Member States                                         ing in Lomé, Togo, they        AFRO Essential Drugs Price Indicator
                             joint bulk purchasing of drugs for prior-        should strengthen the ca-                                       recommended: the crea-         has been launched. Countries continue to
                             ity health problems, and urged WHO to            pacity of drug regulatory The AFRO Essential Drugs Price tion of Directorates of               receive support in implementing national
                                                                                                            Indicator – one of the welcome
                             provide more information to Member               agencies and grant them initiatives introduced by the           Pharmacy and Medicines;        drug policies, assessing drug regula-
                             States on the benefits and limitations of        some degree of autonomy, AFRO Intensified Essential             quality control labora-        tory capacity in Member States and
                             such schemes. However, they insisted             to ensure effectiveness Drugs Programme                         tories; pharmaceutical         reviewing pharmaceutical legislation. ❏




                             Brazil: WHO’s Director-General
                             speaks out for generics
                                     r Gro Harlem Brundtland,                  of pharmaceutical companies’ moral ob-          cost, increasing choice and helping to        transparent legislation exists. The Direc-

                              D      WHO’s Director-General, has
                                     made a major speech in Brazil
                                     strongly supportive of generic
                                                                               ligation to contribute to the solution, but
                                                                               also said that protective tariff barriers and
                                                                               distribution margins for drugs should
                                                                                                                               rationalise both the selection and use of
                                                                                                                               pharmaceuticals.
                                                                                                                                                                             tor-General pointed out that in the USA
                                                                                                                                                                             generic drugs represent half of the mar-
                                                                                                                                                                             ket in volume. One of the European
                             drug strategies. Testifying before the            come down. Dr Brundtland highlighted            Relevance for the                             Union’s three major policy regulations on
                             country’s Parliamentary Commission on             the need for political acceptance of the        private sector                                pharmaceutical pricing and reimburse-
                             Investigation of Medicines in April 2000,         concept of “equity pricing”, especially for                                                   ment is to enhance competition by making
                                                                                                                                   Dr Brundtland told Commission
                             she discussed national drug policies,             newer essential drugs of vital public                                                         the market more transparent and encour-
                                                                                                                               members that policies advocating gener-
                             essential drugs and the importance of             health importance. Equity pricing means                                                       aging generics. And many hospitals in
                                                                                                                               ics – which are frequently only associated
                             generics in promoting affordability of            that the poor would not have to pay the                                                       developed countries have lists of ap-
                                                                                                                               with the public sector – can be just as
                             medicines.                                        same price for life-saving drugs as those                                                     proved drugs which identify products by
                                                                                                                               beneficial in the private sector, because
                                 Saying that there are no “simplistic          who are better off. She urged govern-                                                         generic name.
                                                                                                                               they promote efficiency within pharma-
                             solutions and no magic bullets”, Dr               ments of industrialised countries to lead                                                         In conclusion, Dr Brundtland said
                                                                                                                               ceutical markets. She stressed the
                             Brundtland explored how people living             in its establishment. While developing                                                        that WHO has, for a long time, been en-
                                                                                                                               importance of this in developing coun-
                             in poverty might get sustainable access           country governments must facilitate                                                           couraging drug policies based on the
                                                                                                                               tries, where up to 90% of drug con-
                             to drugs at affordable prices. She spoke          access by “improving financing, impor-                                                        promotion of generic drugs of assured
                                                                                                                               sumption is through the private sector.
                                                                                               tation, purchasing and                                                        quality – a cost-effective strategy in
                                                                                                                               She added that generic strategies in-
                                                                                               distribution systems for                                                      containing drug expenditure. She told
                                                                                                                               volve much more than legal mandates;
                                                                                               medicines, vaccines and                                                       Commission Members that WHO is,
                                                                                                                               “they need support and enforcement, must
                                                                                               medical equipment”, Dr                                                        therefore, in favour of so called “early
                                                                                                                               respond to the concerns of involved par-
                                                                                               Brundtland continued.                                                         workings” of patented drugs for generic
                                                                                                                               ties and provide adequate economic
                                                                                                   Brazil’s National Drug                                                    manufacturers, to encourage competition
                                                                                                                               incentives”.
                                                                                               Policy highlights generic                                                     and give impetus to research for improved
                                                                                               drug prescribing and use,                                                     products. This includes the use of pat-
Photo: WHO/PAHO/C. Gaggero




                                                                                               and stipulates mandatory
                                                                                                                               More countries adopt                          ented drugs for research and testing,
                                                                                               adoption of generic names       the strategy                                  which necessitates prompt registration
                                                                                               in all public purchases.            Dr Brundtland spoke of the progress       and early production of generic drugs, the
                                                                                               The Director-General said       made to date. In Latin America, several       Director-General said. Countries with
                                                                                               that promoting generics         countries have already enacted legislation    variations of early workings provisions
                                                                                               can help meet the ob-           relevant to generic strategies, but in most   include Argentina, Australia, Canada,
                                                                                               jectives of health sector       cases implementation is limited. Overall,     Hungary, Israel and the USA. ❏
                             A young patient in Brazil, where generic drugs are rapidly        reforms by improving            however, the results indicate that lower
                             increasing their share of the pharmaceutical market               affordability, reducing         prices have resulted where solid and                         ■    ■   ■


                                                                                                                                                                                     Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                          21




  NATIONAL                    DRUG             POLICY



Launch of the Australian                                                                                                                                                Nevertheless, our comprehensive policy
                                                                                                                                                                        has finally won the endorsement of Gov-
                                                                                                                                                                        ernment and with this endorsement goes
National Medicines Policy                                                                                                                                               the expectation that continuing resources




                                                                                                                                               Photo: WHO: H. Anenden
                                                                                                                                                                        will be made available to ensure that we
                                                                                                                                                                        can implement strategies in the many ar-
         ➢ ANTHONY SMITH*                          In line with the prototype policy                                                                                    eas which are currently less than ideal. It
                                               elaborated by WHO, rational use (or qual-                                                                                would have been good to have had this
         ustralia has gained a reputation as   ity use, as we chose to call it) of medicines                                                                            policy and its endorsement a long while

 A       an innovative country for its work
         on the quality of use of medicines,
         and for its recently established
                                               became the fourth component of Austra-
                                               lian policy in 1992. Therefore, our
                                               Medicines Policy evolved over a long
                                                                                               Aborigines in Kalgoorlie, Australia. Adoption
                                                                                               of the National Drug Policy has formalised
                                                                                               the country’s efforts to provide quality
                                                                                               medicines for all
                                                                                                                                                                        ago!
                                                                                                                                                                            The Australian Medicines Policy
                                                                                                                                                                        document may be accessed and down-
National Prescribing Service. It may           period in contrast to that of many coun-                                                                                 loaded from: http://www.health.gov.
therefore come as a surprise to learn that,    tries who have devised theirs over a                                                                                     au:80/haf/docs/nmp2000.htm ❏
                                                                                               separate evaluation committee for these
until recently, Australia had no formal,       period as short as a few months.
                                                                                               products).
comprehensive, endorsed National Me-               At last, and primarily through the
                                                                                                  As a country we have been very                                        * Anthony Smith is Professor of Clinical Phar-
dicines Policy. The reasons are historic       work of the Australian Pharmaceutical
                                                                                               fortunate that several of the essential                                  macology, Newcastle University Mater
rather than political.                         Advisory Council (APAC), all this activ-
                                                                                               ingredients of a National Medicines                                      Misericordiae Hospital, Waratah NSW
    For more than 50 years, acceptable         ity has come together in the National
                                                                                               Policy have been in existence for so long.                               2298, Australia.
quality, safety and efficacy of medicines      Medicines Policy which was formally
have been assured through the work of          launched by the Joint Parliamentary
the Therapeutic Goods Administration.          Secretary for Health, Senator Grant
    Equity of access to medicines is pro-      Tambling, on 10 December 1999.
vided through the Pharmaceutical
Benefits Scheme which, by a system of
                                                   APAC was a good vehicle for the de-
                                               velopment of the Policy document as its
                                                                                               Progress on drug policy
graduated co-payments, allows access to
medicines for all including the poorest
                                               membership reflects the partnership ap-
                                               proach which has become central,                in FYR Macedonia
members of society – in the extreme at         particularly, to the Quality Use of Me-
no cost to the consumer. This Scheme has       dicines Programme in Australia. Con-                     he Former Yugoslav Republic of Macedonia launched its National Drug Policy
operated for half a century.
    While the pharmaceutical industry
may have some ambivalence about its re-
                                               sumers, the pharmaceutical industry,
                                               government and health professionals are
                                               all represented on APAC. The document
                                                                                                 T      development process in February 2000, with the support of WHO/EURO and
                                                                                                        WHO Humanitarian Assistance Office, Skopje.
                                                                                                           Five working groups were created to develop different elements of policy:
lationships with government, financial         reflects all of their views including, most     legislation and regulations; drug selection; drug information; rational drug use; supply
incentives have been provided to enhance       recently, those relating to the community       and economic strategies; and human resource development. By October the groups
industry’s viability, both in Australia        role of complementary medicines (Aus-           were ready to move to the next phase of the process – combining the different drafts
and as a presence in the South-East            tralia has a Federal Government Office          to produce one comprehensive document. Macedonia is now deciding on future
Asia/Western Pacific region.                   for Complementary Medicines and a               activities and a time frame for policy implementation. ❏


  NEWSDESK




World Health Assembly 2000:
                                                                                                                                                                        of the problem. The audience was told of
                                                                                                                                                                        highly sophisticated operations in which
                                                                                                                                                                        criminals take advantage of cross-border
                                                                                                                                                                        loopholes. Supplies, production, shipping

drug debates focus on HIV/AIDS                                                                                                                                          re-labelling, financing and distribution of
                                                                                                                                                                        these drugs are often handled in different
                                                                                                                                                                        countries.
         comprehensive resolution on           Numerous delegates stressed the need            their voices to support for WHO’s role in                                    The meeting called for closer coop-

 A       HIV/AIDS was among the high-
         lights of the World Health Assem-
         bly, held in Geneva in May 2000.
                                               for WHO to retain its independent voice
                                               when advising countries on the com-
                                               plex subject of health-related aspects of
                                                                                               providing global pricing information on
                                                                                               quality medicines for people living with
                                                                                               HIV/AIDS.
                                                                                                                                                                        eration between law-enforcing agencies,
                                                                                                                                                                        legislative bodies and the pharmaceuti-
                                                                                                                                                                        cal industry. Saying that there was “an
Ninety-five percent of the 34 million          trade.                                                                                                                   urgent need for action”, Dr Yasuhiro
people living with HIV/AIDS are in                 At one of the many side meetings dur-       Tackling counterfeit drugs                                               Suzuki, Executive Director of WHO’s
developing countries. And it was these         ing the Assembly, public health advocates           A well-attended technical briefing on                                Health Technology and Pharmaceuticals
countries’ representatives who success-        from Health Action International, Mé-           drug quality at the Assembly focused on                                  Cluster, referred to the “deadly combina-
fully campaigned for WHO to increase           decins Sans Frontières and Consumer             counterfeits. The presence of senior health                              tion of demand for cheap drugs and fat
its role in advising on the best treatment     Project on Technology held a joint brief-       officials, and representatives from Inter-                               profit margins” that makes counterfeiting
options, and how to overcome drug              ing for Member States on improving              pol, the pharmaceutical industry and                                     drugs so attractive to criminals and such
pricing and access problems. During            access to essential drugs. And they added       NGOs reflected the multi-faceted nature                                  a threat to society. ❏
discussions on the Revised Drug Strat-
egy delegates also stressed the need for
WHO to support broader approaches to
drug financing, and to address the grow-
ing dangers of unregulated sale of             Bridging the digital divide
medicines on the Internet and counterfeit
drugs.                                                 nly a small fraction of global          medical and health research institutions                                 negotiating with service providers in the
    Among its provisions resolution
WHA53.14 on confronting the HIV/
AIDS epidemic requests the Director-
                                                O      health research expenditure goes
                                                       to research into diseases and
                                                       health issues that affect the
                                                                                               in Africa, Central Asia and Eastern Eu-
                                                                                               rope with Internet access to quality
                                                                                               scientific information from around the
                                                                                                                                                                        eight initial countries to provide high-
                                                                                                                                                                        speed connection to the Internet. Research
                                                                                                                                                                        staff in the countries will receive com-
General to: support the implementation         poor, such as malaria, killer childhood         world.                                                                   prehensive training to ensure maximum
of drug price monitoring systems in Mem-       diseases and nutrition. One step towards            The project’s first year pilot phase                                 benefit from the project. It is anticipated
ber States, to promote equitable access to     changing this is to facilitate research         will enable scientists at leading research                               that by the end of its second year between
care, including essential drugs; promote       in the countries that have first-hand           institutions in Armenia, Ghana, Mali,                                    30 and 40 countries will have joined
rational use of drugs by strengthening         experience of these problems. Now               Mozambique, Mongolia, Uganda, Tanza-                                     the project, which is part of the wider
Member States’ capacity to implement           WHO and the Open Society Institute              nia and Uzbekistan to access information                                 United Nations programme “Health
drug monitoring systems; and continue to       (part of the Soros Foundation network)          in digital format. In this way integration                               InterNetwork”. This aims to improve pub-
develop methods and support for moni-          have teamed up with information provid-         of the world scientific community                                        lic health world wide by facilitating the
toring the pharmaceutical and public           ers ISIO and SilverPlatter, and other           through electronic communication will                                    flow of health information using Internet
health implications of trade agreements.       partners to do just that. They will provide     advance. WHO will be among those                                         technologies. ❏

Issue No. 28 & 29, 2000
22                                                                                                                              ESSENTIAL DRUGS MONITOR




  ACCESS




WHO and partners – taking the
initiative to make a healthier world
      here are several important and new international health initiatives involv-              intensive final phase in order to mop up                                        For more news on the Polio Eradi-

  T   ing WHO in global partnerships that are addressing some of the most
      pressing health problems of our time. Here we focus on some of them,
      beginning with WHO Director-General Gro Harlem Brundtland’s call for
                                                                                               the final pockets of the virus.
                                                                                                   In September 2000, a broad spectrum
                                                                                               of leaders from business, governments,
                                                                                                                                                                            cation Initiative check: www.who.int/
                                                                                                                                                                            vaccines-polio/

a concerted global effort to tackle diseases of poverty, made in October 2000.                 UN agencies and humanitarian groups,                                                    STOPPING TB
                                                                                               met at the United Nations in New York
                                                                                               to galvanise the necessary financial re-                                         Tuberculosis (TB) remains the larg-
    Opening a meeting of 200 health and            assessment of health systems and            sources and political will for the Initiative                                est killer of young people and adults in
advocacy experts from 70 countries in              international development efforts.          to ensure it meets the 2005 deadline. Over                                   the world, and the problem is growing
Winterthur, Switzerland, Dr Brundtland             Since its inception the Alliance has        250 participants pledged to help over-                                       with the spread of HIV/AIDS and drug
said that although the world had long          received a great deal of interest from de-      come the challenges: poliovirus was still                                    resistant strains of the disease. Stop TB
known that illness and poverty are closely     veloping countries wanting to benefit           circulating in up to 20 countries at the end                                 is a global movement to accelerate social
linked, recent data show a much more           from its work. On 20th September 2000           of 2000, and US$450 million in new fund-                                     and political action to stop the unneces-
devastating economic impact on devel-                                                                                                                                       sary spread of TB around the world. Its
                                               the Global Vaccine Fund, one of the             ing is needed to conquer the disease in
oping country economies by a few                                                                                                                                            mission is to ensure that every person with
                                               financial tools used by the initiative, an-     those places. The 20 high-risk countries
infectious diseases, particularly malaria,                                                                                                                                  TB has all the necessary information
                                               nounced that it will be giving more than        also present some of the most difficult
HIV/AIDS and tuberculosis. But a                                                                                                                                            and access to treatment and cure. Stop
                                               US$150 million worth of vaccines and            logistical challenges to polio eradication,
number of effective health interventions                                                                                                                                    TB is a partnership working with public
                                               funding over five years to improve im-          including populations that are geogra-
exist that dramatically reduce mortality                                                                                                                                    and private organizations from the local
                                               munization rates in Africa, Asia and Latin      phically isolated and, in a handful of                                       to the global level. Donors, research in-
of these killers, she emphasised. “Quite       America. According to estimates more            countries, living in the midst of severe                                     stitutions, industry, international agencies,
simply, if we can take these interven-         than 100,000 lives will be saved every          civil conflict. Emphasising the urgency                                      governments and NGOs are all playing
tions to scale – and by that I mean to a       year due to initial grants to 13 countries.     of the task, UN Secretary-General, Kofi                                      a role in:
global scale – we have in our hands a              For further information check:              Annan, said that “our race to reach the
concrete, result-oriented and measurable       www.who.int/vaccines/aboutus/gavi.htm           last child is a race against time. If we do                                  ➤ linking TB control to health sector
way of starting to reduce poverty.” Dr                                                         not seize the chance now, the virus will                                       development;
Brundtland said that a concerted global                                                                                                                                     ➤ linking TB control to poverty allevia-
                                                  ROLLING        BACK MALARIA                  regain its grip and the opportunity will
                                                                                                                                                                              tion;
effort was needed that would involve a                                                         elude us forever”.
process, a road to follow, a framework for         When she became WHO’s Director-                                                                                          ➤ linking TB control to relevant aspects
thinking and a set of values to underpin       General in 1998, Dr Gro Harlem                  A recent milestone                                                             of socioeconomic development;
it all.                                        Brundtland decided that malaria would be                                                                                     ➤ promoting a more client-centered
                                               one of the Organization’s top priori-               The WHO Western Pacific Region
    The forum followed recent announce-                                                                                                                                       approach for wider coverage and
                                               ties. She instigated Roll Back Malaria,         was certified polio-free on 29 October
ments by the G8 leading industrial nations                                                                                                                                    compliance by partnering with
                                               a partnership involving a wide range            2000 by an independent panel of interna-
of targets to reduce the burden of malaria                                                                                                                                    community-based groups and others.
                                               of organizations at country, regional           tional public health experts. The Region
and tuberculosis by 50% within 10 years,                                                                                                                                        For further information check:
                                               and global levels. The initiative’s goals       includes 37 countries and areas ranging
and to reduce the spread of HIV/AIDS                                                                                                                                        www.stoptb.org/stop.tb.initiative/index.
                                               include:                                        from tiny islands to China with a popula-
by 25% within the same time period. It                                                                                                                                      html#StopTB
                                                                                               tion of 1.2 billion people. The Regional
also comes after the creation of a new         ➤ support to endemic countries in devel-                                                                                         One of Stop TB’s partners is the Glo-
                                                                                               Certification Commission on Poliomyeli-
policy framework by the European Com-            oping their national health systems                                                                                        bal Alliance for TB Drug Development,
                                                                                               tis Eradication confirmed that no new
mission intended to focus the European           as a major strategy for controlling                                                                                        a not-for-profit venture that is accelerat-
                                                                                               cases of indigenous polio have been de-
Union’s aid effort on reaching those             malaria;                                                                                                                   ing the discovery and development of new
                                                                                               tected in the Western Pacific in the last
targets.                                                                                                                                                                    drugs to fight the disease by drawing upon
                                               ➤ efforts to develop the broader health         three years, despite excellent surveillance
                                                 sector – all providers of health care to      for the virus – the major benchmark for                                      best practice and resources from the pub-
                                                 the community. This includes the pub-                                                                                      lic and private sectors (see page 19). The
      ACCESSING         VACCINES                                                               certification.
                                                                                                                                                                            Alliance aims to fill a gap in TB drug
                                                 lic sector health system, civil so-
    Every year, nearly three million chil-       ciety, NGOs and private health                                                                                             development by using a lean research and
dren die from diseases that could be             providers (including drug ven-                                                                                             development operating model that
prevented with currently available               dors and traditional healers) and                                                                                          outsources projects to public or private
vaccines. The Global Alliance for                others;                                                                                                                    partners. It will survey all TB drug de-
Vaccines and Immunization (GAVI),                                                                                                                                           velopment and selectively intervene when
                                               ➤ encouragement to obtain the                                                                                                its actions will help move a drug candi-
formed in 1999, is a coalition of interna-         necessary human and financial                                                                                            date towards registration and use in
tional organizations, with a mission to            investments for health system                                                                                            therapy. In this way the Global Alliance
ensure that every child is protected against       development.                                                                                                             will build a portfolio of projects with
vaccine-preventable diseases. It wants
                                                   In recent months Roll Back Ma-                                                                                           varying levels of funding, management
to close the growing gap in the number
                                               laria has received a major boost from                                                                                        and ownership.
of vaccines available to children in                                                                                                                                            Further information is available at:
                                               the African summit meeting, which
industrialised and developing countries.                                                                                                                                    www.tballiance.org/home.cfm
                                               set the agenda for the continent’s
GAVI is working to:
                                               efforts to beat the disease (see report
➤ improve access to sustainable immu-          on page 23).                                                                                                                     IMPROVING       INJECTION
  nization services;                               Find out more at: www.rbm.
                                               who.int                                                                                                                                    PRACTICES
➤ expand the use of all existing cost-
                                                                                                                                                                                Injections are predominantly needed
  effective vaccines;
                                                   ERADICATING          POLIO                                                                                               for the treatment of severe diseases,
                                                                                                                                               Photo: WHO/PAHO/C. Gaggero




➤ accelerate the development and intro-                                                                                                                                     mostly in hospital settings. Nevertheless,
  duction of new vaccines;                         The Polio Eradication Initiative                                                                                         they are overused to administer medica-
                                               is on track to certify global eradica-                                                                                       tions in many countries because of an
➤ accelerate research and development          tion of the disease in 2005, with more                                                                                       ingrained preference for injections among
  efforts for vaccines and related prod-       than 190 countries and territories                                                                                           health workers and patients. In develop-
  ucts specifically needed by developing       which will have interrupted polio-                                                                                           ing countries up to 50% of injections
  countries;                                   virus transmission by the end of the                                                                                         are administered with re-used syringes
➤ make immunization coverage an                year 2000. This is an initiative that     A sight that will soon disappear? A polio victim                                   and needles. Such unsafe practices have
  integral part of the design and              began in 1988, but it is entering an      learns to walk with callipers                                                      been linked to the transmission of many

                                                                                                                                                                                     Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                         23




  ACCESS




                                                              New drugs needed to fight TB
pathogens between patients, including the
hepatitis, HIV, Ebola and dengue fever
viruses, and the malaria parasite.
    The Safe Injection Global Network
(SIGN) is a coalition of several public
and private partners, including WHO,                                   ore than 120 tuberculosis (TB)        Mixed panels discussed the pharmaco-                      The meeting discussed accelerating
UNICEF, UNAIDS, NGOs, govern-
ments, universities, health workers and
industry. Formed in Geneva in October
                                                               M       and public health experts, govern-
                                                                       ment and industry representa-
                                                                       tives, researchers and donors
                                                                                                             economics of the TB drug market, which
                                                                                                             is predicted to be US$700 million for
                                                                                                             treating 10,000,000 TB patients world-
                                                                                                                                                                   the development of new TB drugs to im-
                                                                                                                                                                   prove prevention and treatment of the
                                                                                                                                                                   disease. It also decided to develop a de-
1999, it aims to unite the partners’                          discussed TB drug development at a two-        wide by 2008. The general opinion was                 dicated Global Alliance for TB Drug
strengths and skills to work together on                      day workshop in Cape Town, South               that the size of this market should enable            Development, with partners from aca-
injection safety. Because there have been                     Africa, in February 2000. They met be-         the development of at least one or two                demia, industry, major agencies, NGOs
few integrated programmes that link com-                      cause of the urgent need for new drugs to      new drugs.                                            and donors worldwide.
munity and health systems to promote                          ensure shorter TB treatments and to fight          But some participants argued that
safe injection use, SIGN is coordinating                      the increasing resistance to existing drugs.   there was a reluctance to develop drugs               From vision to fruition…
the launch of pilot projects in five coun-                    Basic TB drugs are already 20–30 years         for a market where most of the people are
tries. Results of the pilot projects’                         old, and few new drugs have been               poor, and where developing countries,                     By October 2000 the participants’
evaluation should be available by 2002,                       marketed in recent years.                      institutional buyers and agencies work-               push for a Global Alliance for TB Drug
and will enable the Network to identify                           TB experts, including WHO repre-           ing on TB demand low prices. A                        Development became a reality with its
and adopt successful strategies to                            sentatives, described the need for new TB      guaranteed off-take or market would be                launch by WHO’s Director-General, Dr
counter unsafe injections.                                    drugs, researchers presented promising         a strong incentive for manufacturers.                 Gro Harlem Brundtland, at a meeting in
                                                              state-of-the-art research methods and          There was a view that “corporate aware-               Bangkok. And in February 2001 the Alli-
                                                              findings, and drug companies explained         ness” of the problem is increasing. Some              ance opened its head office in Cape Town,
Positive developments
                                                              the difficulties of drug development.          companies have specific TB projects, oth-             South Africa, to coordinate and fund
    SIGN’s annual meeting, held in Cairo                                                                             ers are considering “donating” the            research in tuberculosis in developing
in October 2000, showed that there has                                                                               licensing rights of economically              countries.
already been progress. For example, Pa-                                                                              less viable second-line TB drugs                  The main aim is to find a major new
kistan has set up a national “SIGN” group,                                                                           to public bodies.                             treatment for TB by 2010, specifically a
Tanzania has launched an education cam-                                                                                                                            drug that is more effective so that it needs
paign for the public and health workers,                                                                                                                           to be used for a shorter time, reducing the
and Burkina Faso has made significant
                                                                                                                     Not only money…
                                                                                                                                                                   treatment period by at least 50 per cent,
improvements in injection safety recently.                                                                               Many participants warned that             and so increasing adherence.
Participants reviewed the previous year’s                                                                            low cost drugs or even donations                  The Alliance will not to set up its own
activities, exchanged information and                                                                                are no guarantee of solving the TB            research institutions but will support ex-
coordinated their advocacy and public                                                                                problem, as managerial problems               isting projects, particularly in developing
awareness activities.                                                                                                in many countries with mid level              countries, and coordinate their findings.
    New technical guidelines on prevent-                                                                             economies have meant that they                The first funding allocations will be made
ing infection from injections are being                                                                              have only achieved 50–60% cure                in April 2001. ❏
prepared, and a provisional document                                                                                 rates. Poor patient adherence
                                                Credit: WHO




open for comments from the public will                                                                               after the first two months of a six-
be available on the SIGN Web site:                                                                                   month treatment period increases              For further information on the Global Alliance
www.injectionsafety.org ❏                                                                                            the risk of drug resistance.                  for TB Drug Development see page 22.




Beating malaria:
leaders pledge action at historic summit
         alaria, a disease that is prevent-                     years of age and pregnant women,             re-emergence of malaria;

 M       able, treatable and curable, kills
         one million people a year in
         Africa, with nine out of 10 cases
                                                                benefit from the most suitable combi-
                                                                nation of personal and community
                                                                protective measures. These include in-
                                                                                                             provide reliable information
                                                                                                             on the disease to decision-
                                                                                                             makers at all levels; and to
occurring in the sub-Saharan region.                            secticide treated mosquito nets and          reduce or waive taxes and
Now, the first summit of African heads                          other accessible and affordable inter-       tariffs for mosquito nets,
of state to focus on the disease has com-                       ventions, to prevent infection and           insecticides, anti-malarial
mitted to intensive efforts to halve malaria                    suffering;                                   drugs, and other goods and
mortality by 2010. Held in Abuja, Nigeria,                    ➤ at least 60% of all pregnant women           services needed for malaria
in May 2000, the summit was attended                            who are at risk of malaria, especially       control strategies.
                                                                                                                                                                                                                        Photo: WHO/RBM




by representatives of forty-four of the fifty                   those in their first pregnancies, have
malaria-affected countries in Africa. Also                      access to chemoprophylaxis or pre-           Hidden costs
present were officials from United Na-                          sumptive intermittent treatment.             reinforce urgency
tions agencies and major international
                                                                                                                 The summit’s impor-
donors. The meeting culminated in the                         Commitment, targets                            tance was reinforced by The world’s biggest bednet was erected at Abuja as a symbol
signing of the Abuja Declaration and the                      and resources                                  simultaneous publication of the 225 African children who die every two and a half
Plan of Action in which the leaders re-                                                                                                      hours from malaria
                                                                  The Heads of State called upon all         of a report showing that the
solved to initiate sustainable actions to
                                                              countries to undertake and continue health     cost of malaria is substan-
strengthen health systems, so that by
                                                              systems reforms that will promote com-         tially greater than economists previously      But the longer-term costs are even more
2005:
                                                              munity participation in rolling back           estimated. According to the report,1 the       devastating to the country, the report
➤ at least 60% of those suffering from                        malaria, and so increase sustainability.       disease results in a loss of economic          argues. ❏
  malaria have prompt access to, and are                      Diagnosis and treatment of malaria             growth of more than one percentage point
  able to correctly use, affordable and                       should be available as peripherally as         per year.                                      Reference
  appropriate treatment within 24 hours                       possible (including home treatment), and           Previous estimates have looked only        1. Gallup JL, Sachs JD. Economics of malaria. Centre for
  of the onset of symptoms;                                   accessible to the poorest.                     at immediate short-term financial                  International Development, Harvard University and the
                                                                                                                                                                London School of Hygiene and Tropical Medicine.
➤ at least 60% of those at risk of ma-                            Amongst other things the signatories       implications, such as the loss of labour           (Forthcoming). Executive summary available on the Web
  laria, particularly children under five                     to the Declaration pledged to: prevent         and the costs of treatment and prevention.         at: http://www.malaria.org/jdsachseconomic.html



Issue No. 28 & 29, 2000
                                  24                                                                                                                                          ESSENTIAL DRUGS MONITOR




                                    ACCESS




                                  NGO meetings on drug access
                                          ollowing their successful confer-               The presentation of a new study show-

                                    F     ence on compulsory licensing
                                          held in Geneva in March 1999
                                          (see EDM-27), Médecins Sans
                                                                                      ing that East Africans pay more than
                                                                                      Europeans for life-saving drugs1 was one
                                                                                      of the conference highlights. Among
                                                                                                                                                           Five key messages from WHO on
                                                                                                                                                       trade agreements and pharmaceuticals
                                  Frontières, Health Action International             the many examples cited in the study
                                  and the Consumer Project on Technology              is that of the antibiotic, ciprofloxacin,
                                  have organized two more meetings on one             which was found to be twice as expen-                                                             ◆    ◆    ◆
                                  of today’s most topical issues. A con-              sive in Uganda as in Norway. Another                         “First, patent protection is a necessary and effective incentive for research and
                                  ference entitled Increasing Access to               example is fluconazole, a treatment for                      development for needed new drugs. Essential drugs are a public good and not
                                  Essential Drugs in a Globalised Economy             AIDS-related meningitis. In Thailand,                        simply just another commodity. Patents must therefore be managed in an impartial
                                  – Working Towards Solutions, brought                where generic competition has lowered                        way to benefit both the patent holders and the public.
                                  together 350 people from 50 countries in            prices, fluconazole costs only US$0.30.                      Protectionism has never benefited public health. WHO supports governments to enact
                                  Amsterdam in November 1999. Health                  However, the same drug costs US$18.00                        national legislation which can draw advantage from more open trade and a better
                                  advocates and public health profes-                 in Kenya, where it is patent protected.                      regulated international system. And we support governments in incorporating the
                                  sionals from developing countries,                      Participants argued that the reasons                     safeguards that have been built into the WTO TRIPS Agreement to protect the rights
                                                                                            medicines are expensive in East                        of the public.
                                                                                            Africa include high tariffs, taxes and                 Second, priority-setting for research and development in the pharmaceutical market
                                                                                            lack of generic competition as well                    is imperfect. There are also striking market failures when there is such desperate
                                                                                            as strong patent protection. Discus-                   demand for products that are available – but not within reach of those in need.
Photo: Médecins Sans Frontières




                                                                                            sion focused on strategies to enact                    WHO has initiated, with other partners, innovative mechanisms to stimulate research
                                                                                            legal safeguards to remedy the cur-                    and development in areas of high public health need, such as malaria and tuber-
                                                                                            rent situation. Delegates heard that,                  culosis. Through its Medicines for Malaria Venture (MMV), the Global Alliance for
                                                                                            within existing international trade                    Vaccines and Immunization (GAVI) and other initiatives, WHO is actively encourag-
                                                                                            rules, such safeguards include par-                    ing public sector financing for critical public health problems and neglected tropical
                                                                                            allel importing (the right to shop                     diseases.

                                  Intense concentration on the faces of delegates at the
                                                                                            around for the best prices of branded                  Third, WHO strongly supports development of mechanisms for preferential low
                                  Nairobi meeting, which tackled complex and                products) and compulsory licensing                     prices for essential drugs in lower-income countries. Lower-income countries simply
                                  controversial issues                                      (granting limited production rights                    cannot be expected to pay the same price for essential drugs as the wealthier
                                                                                            to generic producers).                                 countries.
                                  representatives from domestic and inter-                Another report presented at the meet-                    For governments, industry, and other stakeholders, there is a range of measures
                                  national NGOs, the pharmaceutical                   ing on patent protection and medicines                       which might be used to achieve preferential pricing. But where there is an abuse of
                                  industry, international organizations, na-          in Kenya and Uganda2, calls on govern-                       patent rights, where patented essential drugs are unavailable or where a national
                                                                                      ments to ensure these safeguards, and to                     emergency exists, recourse to compulsory licensing is a legitimate measure consistent
                                  tional governments and academics all
                                                                                                                                                   with the TRIPS Agreement.
                                  contributed their ideas on how to achieve           include Ministry of Health representatives
                                  access to essential medicines. After two            and health professionals when negotiat-                      Fourth, WHO supports implementation of the TRIPS Agreement to ensure prompt
                                  days intensive work, the Conference cul-            ing and adopting trade agreements. ❏                         availability of generic drugs upon patent expiration. WHO has long promoted use
                                  minated in the drawing up of the                                                                                 of generic drugs of assured quality. Experience from countries with “generic-friendly”
                                  Amsterdam Statement, which includes a                                                                            policies clearly demonstrates that the market competition created by these policies
                                                                                      References                                                   increases affordability of medicines, stimulates true innovation within the research-
                                  recommendation for the World Trade
                                                                                      1. Myhr K. Pharmaceutical pricing: law of the jungle.        based industry, and encourages increased production efficiency by the generic
                                  Organization to create a Standing Work-                 Amsterdam: Health Action International; 2000.            industry.
                                  ing Group on Access to Medicines. The
                                  Group would work within the WTO to                  2. Boulet P. Patent protection of medicines in Kenya and     Finally, trade agreements should not create barriers to trade. An important WTO
                                                                                          Uganda. Geneva: Médecins Sans Frontières; 2000.
                                  consider the impact of trade policies on                                                                         principle is that technical regulations, standards and assessment procedures should
                                  people in developing and least developed                                                                         be based on international standards, guides and recommendations. In the area of
                                  countries. It would provide a public health                                                                      pharmaceuticals, WHO norms, standards and guidelines represent such international
                                                                                      Further information on this series of meetings               consensus. So we will actively promote these guidelines”.
                                  framework for the interpretation of key             on access to essential drugs can be found
                                  features of WTO agreements, and WHO                 at: www.haiweb.org
                                  and other international organiza-
                                  tions would support the activities of the
                                  Working Group.
                                      Among the many thought-provoking
                                  speeches, Dr Gro Harlem Brundtland,
                                  WHO’s Director-General, told delegates                  Trade and access:
                                                                                          Ugandan groups push for progress
                                  that “Making a difference requires the
                                  often painful work to build consensus
                                  among stakeholders that can move things
                                  in the right direction. Health products
                                  and health services are tradable. Health                     he title of a workshop held in                    need to network and to create awareness of key issues using various media. Discus-
                                  products such as pharmaceuticals are pro-
                                  duced, marketed and sold across the globe
                                  – benefiting some but failing to reach too
                                                                                             T Kampala, Uganda, in February
                                                                                               2000, certainly conveyed the
                                                                                               spirit of the event and the breadth
                                                                                                                                                 sions also highlighted the importance of involvement in legislation review and
                                                                                                                                                 formulation (particularly the draft bill on intellectual property rights), and participa-
                                                                                                                                                 tion in Uganda’s National Drug
                                  many. So the rules that regulate this trade         of subjects addressed. “Advocacy and                       Policy review. Delegates were
                                  are key”, she told delegates.                       Campaign for Better Trade, Access to                       urged to campaign for improved
                                      The Director-General listed WHO’s               Essential Medicine and Promoting                           infrastructure. Only when this is
                                  five key public health messages on                  Rational Drug Use in Uganda ” was the                      in place can important develop-
                                  international trade agreements and                  result of collaboration between Uganda’s                   ments get underway, such as
                                  pharmaceuticals (see box).                          Consumers Protection Association,                          offering incentives to open drug
                                                                                      Action Aid Uganda, Health Action                           outlets in poor rural areas. ❏
                                                                                      International and Médecins Sans
                                  Moving on to Africa                                 Frontières.                                                For further information contact:
                                      The NGO campaign on access to es-                   Participants left this lively meeting in               R. Mutambi, Health and Gender
                                                                                                                                                                                                                                              Photo: E. Paterson




                                  sential drugs gathered further momentum             February 2000 determined to push for                       Officer, Uganda Consumers
                                                                                                                                                 Protection Association, Desai
                                  in Nairobi in June 2000. The Kenyan                 better trade policy, improved health serv-
                                                                                                                                                 House, Plot 4, Parliament Avenue,
                                  capital was the venue for the East Africa           ices and increased consumer awareness                      PO Box 23783, Kampala,
                                  Access to Drugs Conference, where rep-              of pharmaceutical issues. They agreed                      Uganda. Tel: + 256 41 234 002,      This ambulance may be stuck in the mud in Uganda, but
                                  resentatives from 21 countries met to               that access to drugs is a crosscutting is-                 Fax: + 234003, e-mail: ucpa@        the description could not apply to campaigners pushing
                                  devise a regional strategy.                         sue, and that to be more effective they                    imul.com                            for improvements in the pharmaceutical sector


                                                                                                                                                                                                          Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                            25




  ACCESS




Transforming drug
supply in Dar es Salaam
                               ➢ KARIN WIEDENMAYER,                                            commitment from the recipient side. The      inventory management was done
                                  DEO MTASIWA*                                                 project bypassed the national procure-       haphazardly and did not follow good
                                                                                               ment system, the former Central Medical      practice. Bin cards were unavailable,
         n 1990 the inadequacy of the pharmaceutical supply system in Dar es                   Stores being unreliable and inefficient.     drug flow monitoring was difficult and

  I      Salaam, commercial capital of the United Republic of Tanzania, was
         evident. There was chronic shortage of drugs at health facilities, supply
         was erratic as was Government funding, drug supply management was
                                                                                               Later the organization was restructured
                                                                                               and became an autonomous department
                                                                                               within the Ministry of Health, under the
                                                                                                                                            documentation was poor.
                                                                                                                                                By 2000, full decentralisation to the
                                                                                                                                            districts was complete, on structural,
poor and use of drugs irrational. Despite a national policy to provide drugs free              responsibility of an external management     administrative and operational levels.
of charge, unofficially patients often had to pay for them. Drugs were purchased               team. In 1996, the new Medical Stores        Pharmacy premises have been reorgan-
from the national Central Medical Stores, which was seen as inefficient, unreli-               Department was operating efficiently, and    ized, and hospital and district pharmacies
                                                                                               it was considered appropriate to start us-   have been physically separated. The sepa-
able and poorly stocked. Drug quality was questionable and pharmacy premises
                                                                                               ing the existing local drug procurement      ration of these premises considerably
were often unsuitable – hot, humid and cluttered with piles of drugs, some of
                                                                                               infrastructure. The Department’s per-        facilitates storage and inventory practice,
them expired. Pharmacists tended to have low professional visibility and not to                formance has been good overall, with an      as well as drug flow monitoring, which
be involved in hospital committees. At a time when studies showed that patients                adequate product range, appropriate          have consequently improved. District
equated availability of drugs with good quality of care1, a survey of user pat-                pricing, good quality and service, and       pharmacies are located within the newly
terns in Dar es Salaam in 1990 reported that “the majority of patients complained              sufficient provision for emergency situa-    constructed district medical offices, at a
that usually health facilities do not have drugs at all”.                                      tions. The Medical Stores Department         distance from the district hospitals.
                                                                                               has become the backbone of the Project’s
    Ten years on and the picture is very       as well as irrational use.                      supply system.
different. Dar es Salaam has a decentral-          In 1984, the Government created the             Drug kits are a good but not optimal     KEEPING TRACK OF DRUGS:
ised supply system with drug requisition       Essential Drugs Programme to provide            solution. Because of their predetermined     MONITORING AND
at district level and local procurement        essential drugs to health facilities. The       contents (selection and quantity) certain    DOCUMENTATION SYSTEM
from a newly restructured Medical Stores       Programme introduced a prepacked drug           items were regularly out of stock, others
                                                                                                                                                 The Project implemented a disease
Department, financed by cost-sharing           kit system, which partially improved the        were piling up and some even expired
                                                                                                                                            and drug monitoring system. Forms were
schemes and Government contributions,          situation for health centres and dispensa-      before redistribution. Quantification
                                                                                                                                            developed for data collection on morbid-
and based on the National Drug Policy.         ries, but not for the hospital sector. And      was therefore introduced at the health
                                                                                                                                            ity, drug consumption and kit distribution.
How was this achieved?                         the foreign financed and operated (by           facilities and ordering is now done by
                                                                                                                                            However these were not used routinely,
    The structural and functional rehabili-    WHO, the Danish International Develop-          decentralised requisition, i.e. the indent
                                                                                               system has gradually replaced the push       little evaluation was done, and little at-
tation of Dar es Salaam’s Government           ment Agency and the United Nations                                                           tempt made to give health facilities
health facilities, based on primary health     Children’s Fund) drug kit system did not        system with prepacked kits. A recent
                                                                                               study on quality of care showed a signifi-   feedback on the data. Follow-up of drug
care principles, started in 1990 with an       help to improve management of the drug                                                       consumption, distribution and perform-
intergovernmental agreement between            sector’s infrastructure.                        cant improvement in drug availability. For
                                                                                               example, the level of availability of four   ance monitoring was almost impossible.
Switzerland and Tanzania, with the Swiss           In the early 1990s, when the Dar es                                                      Drug flow could not be traced and
Tropical Institute as the executing agency.    Salaam Urban Health Project began, Tan-         key drugs rose to 95% in 1998 compared
                                                                                               with 64% in 1992.                            accountability was difficult to enforce.
The overall goal of the Dar es Salaam          zania started to restructure the economy                                                          To improve this situation, a Pharmacy
Urban Health Project, created at this time,    towards a market-oriented environment.                                                       Plan of Operations and a Monitoring/
was, and remains, to improve the health        In the health sector this translated into the   DISTRIBUTION      AND STORAGE
                                                                                                                                            Supervision Form were drawn up with
status of people in the Dar es Salaam re-      appearance of the private profit oriented           Initially drug kits were delivered       all pharmacists. Operational objectives/
gion. As regards drug supply, the main         sector and the introduction of user             monthly to the three district hospital       activities, implementors, a timeframe,
aim was to improve resource adminis-           fees. In 1991, Tanzania formulated the          pharmacies. From there, subsequent           reporting channels and evaluation out-
tration at all levels of care, to create a     National Drug Policy, which aimed to            distribution to the hospitals, health        puts were defined. Several documents and
reliable, efficient and sustainable drug       improve the whole pharmaceutical                centres and dispensaries was the res-        forms have been standardised, incorpo-
management system, addressing both ef-         sector, and ensure a regular supply and         ponsibility of the district pharmacist,      rated in the documentation system and
fective supply and rational use of essential   rational use of essential drugs through-        who supervised all peripheral distribution   used in all health facilities. Today, phar-
drugs.                                         out the country. Later, the Health Sector       and monitoring. Delivery of drugs from       macy management tools are available
    The Project serves three districts each    Reform Action Plan 1996–1999 covered            the district stores to the hospital posed    and are to varying degrees integrated into
with one district hospital, one or two         decentralised district-based drug supply        no problems as they were on the same         district and hospital operational plans.
health centres and a total of about 60         and management, liberalised drug                premises. From the district hospitals the    Documentation and monitoring of drug
dispensaries in urban and semi-rural           procurement, quality assurance, and eq-         kits were distributed by vehicle to health   flow have improved.
areas. In 1990 the population of Dar es        uitable access and affordability of drugs.      centres and dispensaries on a monthly             Security of drugs has always been a
Salaam was estimated at 1.5 million and        Here we highlight the main elements of          basis. Logistics were more problematic
the current population is approximately        the Health Project’s work and how against       and deliveries were often delayed due to                         ...cont’d on page 26 ➠
2.5 million.                                   this background, it has transformed drug        lack of transport, distance
                                               supply in the region.                           and road conditions. Health
                                                                                               workers inspected the kits
THE BACKGROUND: DRUG SUPPLY                                                                    on arrival and documented
HISTORY IN DAR ES SALAAM                       BUYINGDRUGS: WHICH,                             receipt. All reorganized fa-
                                               HOW MUCH AND WHERE?                             cilities had adequate and
    During the late 1960’s the number of                                                       secure drug storage areas.
health units in Tanzania increased con-            Drug need quantification was initially      Functioning cold chain
siderably. This increase and the economic      done by morbidity and later by the con-         equipment was also avail-
crisis of the late 1970’s led to a drug cri-   sumption method. Drug selection was             able, however, storage con-
sis in the public health sector. The lack of   based on the National Essential Drug List.      ditions in district stores were
                                                                                                                                                                                          Photo: K. Wiedenmayer




drugs was caused by: the acute shortage        Drug kits for the Dar es Salaam Health          inadequate, with high tem-
of foreign currency; an increase in access     Project were procured through restricted        peratures and humidity
to health units; people’s greater aware-       international tender. The kit system was        affecting drug quality. Pile-
ness of modern medicines; and wastage          centrally and externally organized, donor       ups and expired drugs that
of drugs due to poor planning, procure-        funded, supplied and imported from              were not disposed of took up
ment, storage, distribution and transport,     overseas, with little or no involvement or      valuable space. Storage and Delivering drug kits to a dispensary in Dar es Salaam

Issue No. 28 & 29, 2000
26                                                                                                                            ESSENTIAL DRUGS MONITOR




  ACCESS


Dar es Salaam...                                 voice. Pharmacists are part of the hospi-      Project. The budget gap has been filled              political support, and improvements
cont’d from pg. 25                               tal and district health management team.       by Tanzanian Government contributions                in management and accounting.
                                                 One pharmacist received training in the        and cost-sharing schemes.                      ➤ A programme to promote rational
major concern. Not all drugs used to reach       UK and all pharmacy staff participated             Currently, all dispensaries and health       drug use has been implemented,
the intended patient. Pilferage and mis-         in the training programme on rational          centres operate a Bamako-type model of           with Standard Treatment Guidelines
appropriation was a significant problem          prescribing (see below).                       a drug revolving fund. Hospitals have            and training of all prescribers in the
that is hard to quantify. Despite there be-                                                     introduced 50% to 80% cost-sharing               districts.
ing sufficient drugs, some patients still                                                       and are supported with donor and, un-
complained about not receiving drugs or          PROMOTING        RATIONAL USE
                                                                                                fortunately irregular, Government con-         Shortcomings
of occasionally being forced to pay. In-             All efforts put into a well functioning    tributions. User fees allowed donor
ternal monitoring also indicated that                                                           contributions to gradually decrease. Gov-      ➤ Management capacity is still insuffi-
                                                 drug supply system can be futile if not
drugs, particularly antibiotics, were used                                                      ernment funding is still essential for           cient (storage, inventory management,
                                                 followed by rational use of drugs by pre-
by health staff for their own and their                                                         hospitals, cost-sharing exemptions, staff        documentation, monitoring of drug
                                                 scribers, dispensers and patients. From its
families’ treatment. However, increased                                                         costs etc., and needs to continue to com-        flow) particularly at district hos-
                                                 inception, the Project has emphasised the
supervision, professional ownership and                                                         plement user fees or future insurance            pital level. Supervision needs to be
                                                 importance of promoting rational drug
accountability are improving the situa-                                                         schemes. The system is no longer depend-         strengthened and accountability
                                                 use. In 1994, a programme was started to
tion. Good inventory practice and drug                                                          ent on donor funds. Long-term sus-               reinforced.
                                                 improve prescribing. A general quantita-
monitoring have helped reduce pilferage.         tive drug use indicator study clarified the    tainability will require continued politi-     ➤ The human resource potential of phar-
Each health facility has a Health Board,         drug use situation. A concurrent qualita-      cal will and Government funding,                 macy staff should be strengthened
so involving the concerned community,            tive study investigated motivations and        together with further improvements in            further (knowledge, skills, motivation
which has also helped to reduce the              underlying causes of prescribing habits        drug supply management and accounting.           and involvement). Quality of care in
problem.                                         and constraints within the system. Prob-                                                        terms of attitude and patient care
                                                 lems identified were overprescribing of                                                         needs improvement.
                                                 antibiotics and injections, low availabil-     REVIEW     OF EXPERIENCE
                                                                                                                                               ➤ Rational drug use needs further pro-
QUALITY     OF DRUGS
                                                 ity of the national Standard Treatment             The objective of drug availability has       motion to improve prescribing
    The main mechanism used for qual-            Guidelines and incorrect prescribing           been achieved with large investments and         behaviour (continuing training and su-
ity assurance of drugs is supplier selection     according to norms. Based on these find-       is one of the Project’s recognised accom-        pervision). Dispensing of drugs needs
and contract conditions with the Medical         ings, interventions were selected and          plishments: visible, appreciated by pa-          attention (training of drug dispen-
Stores Department. However, there is no          implemented to improve prescribing             tients and health workers, and valuable          sers). There is a great need to educate
formal reporting system for drug quality         and quality of care. They include new                                                           patients about drug use.
                                                                                                for the health care system. This has con-
problems. Pharmacists and patients have          Standard Treatment Guidelines, a Drug          tributed greatly to the credibility of Dar     ➤ Dialogue with the private sector is
to learn that they have a right and a duty       Information Manual, concurrent training,
to complain and follow-up on substand-                                                          es Salaam’s health care delivery system          minimal.
                                                 continuing education and supervision.          and the willingness of patients to share
ard drugs. Since 1997, operations and                Since printed material alone has
management at the National Pharmacy                                                             the cost of services.                          Summary of development and
                                                 shown very little effect on prescribing
Board have been restructured in order to                                                            Professionally defined quality of care     achievements of Dar es Salaam
                                                 practices, continuing education and su-
enforce drug regulation and quality as-                                                         relating to drugs (availability, prescribing   Urban Health Project drug supply
                                                 pervision are necessary tools to assure        practice, drug quality) has improved,
surance. More recently a new quality             sustained impact. Training sessions were
                                                                                                whereas community perceived quality of           Drug related            1990                        2000
control laboratory has begun operating.          conducted in all districts. Within five
                                                                                                services (dispensing practice, patient care,     activities
                                                 months a total of 328 Project prescribers
                                                                                                affordability) is less enthusiastic.




                                                                                                                                                                                                       ➔ ➔ ➔ ➔ ➔
                                                 (80%) in the three districts’ health facili-                                                    Selection               Appropriate
BEINGIN CHARGE OF DRUGS:
                                                 ties were trained. Unfortunately, despite




                                                                                                                                                                                                         ➔ ➔ ➔
                                                                                                Achievements                                     Procurement             Foreign kit import
HUMAN RESOURCES AND TRAINING                                                                                                                                                                (kits being phased out)
                                                 the existence of approved tools and an
                                                                                                ➤ The Project has a functional drug              Distribution            Deficient
    At the beginning, the Project’s phar-        agreed schedule, planned activities for
macists generally had limited manage-            continuing education and supervision are         supply system in place that assures            Storage                 Poor
ment skills – a major reason why the drug        not yet conducted in a systematic way.           continued availability of essential            Monitoring and          Poor
supply system functioned poorly. Today,                                                           drugs at Dar es Salaam public health            documentation
                                                                                                  facilities. The drug supply system is          Quality assurance       Poor
                                                                                                                                                                                                       ➔
each district has a district pharmacist op-
erationally responsible for supervision of       PAYING     FOR DRUGS                             decentralised and integrated as part            & security
district health facilities, including district       After liberalisation of the health sec-      of the general district management             Promotion of            Irrational use
                                                                                                                                                                                                       ➔

hospitals. Hospital pharmacists are more         tor, a 1995 study identified that about 35%      structure within a reformed health               rational drug use
involved in the usual drug supply man-           of the population used public health fa-         organization in the framework of               Management              Poor
                                                                                                                                                                                                       ➔ ➔ ➔




agement activities, such as quantification,      cilities as first contact. It was estimated      health sector reform. Pharmacists
                                                                                                                                                 Training                None
procurement, storage and distribution of         that drug expenditure for essential              have gained a voice, are more
                                                                                                                                                 Financing               Donor dependent
                                                                                                                                                                                                       ➔




drugs, as well as in some clinical activi-       drugs to all public health facilities of         involved, better informed, more inter-                                                  (reduction in dependence)

ties within hospital committees and in           the City Council amounted to between             ested in their work and more present
drug information. However, pharmaceu-            US$0.7million and US$1.1million a year.          in the system.
                                                                                                                                                 Indicators              1990                        2000
tical management capacity, particularly at       This represents a yearly per capita drug
                                                                                                ➤ A purchase agreement with the Medi-
district level, remains weak and should          expenditure of about US$1 to 1.5, which                                                         Availability            Poor
                                                                                                                                                                                                        ➔
                                                                                                                                                                                                        ➔




                                                                                                  cal Stores Department constitutes the
be strengthened. Decentralisation needs          is in line with the generally accepted fig-                                                     Affordability           Free                             *
                                                                                                  basis for local procurement of drugs.
to be founded on capacity-building at            ure for essential drugs coverage in Africa3.
                                                                                                  Drugs are of good quality since most           Quality                 Poor
                                                                                                                                                                                                        ➔ ➔ ➔ ➔
                                                                                                                                                                                                              ➔




local level.                                     A recent study concluded that drugs ac-
                                                                                                  are bought from a reputable non profit         Rational use            Poor
    With the focus on general district           count for 40% of the total governmental
                                                                                                  international procurement agency.
                                                 and external health expenditures at Dar                                                         Sustainability          No
                                                                                                                                                                                                          ➔




management in the Project’s early years,
                                                                                                  Storage and inventory practice has
training for pharmacists did not receive         es Salaam level.                                                                                Quality of care         Poor
                                                                                                  improved. Monitoring and documen-
the necessary attention. Human resources             From 1992 until 1996, the City Coun-
                                                                                                  tation tools are available and partially
were neglected. Only much later were             cil health facilities were supplied with
                                                                                                                                               ➔ ➔
                                                                                                                                                 ➔




                                                                                                  used. The indent system (drug requi-           significant improvement
the district pharmacists and pharmacy            essential drugs financed by an untied non-
                                                                                                  sition) has been introduced and kits           some improvement
technicians consulted, and invited to dis-       reimbursable allocation from the Swiss
                                                                                                  are gradually being phased out.              * Cost-sharing/full cost recovery with little
cussions and activities aimed to improve         Government. In 1993, the Tanzanian Par-                                                         change in attendance rates, exemption
the drug supply system. Pharmacists have         liament allowed health services to be          ➤ Drugs are financed by full drug cost-          policy
therefore mainly been responders to              charged for. Cost sharing was introduced         recovery at dispensaries and health
change rather than reformers themselves,         in Dar es Salaam public hospitals as in          centres, and by cost sharing at hospi-
even though policy implementation                the rest of the country. A pilot Bamako-         tals. Attendance rates have changed          LESSONS          LEARNT
and operational planning in part depend          type project successfully implemented            little, and exemption policies are in           The Dar es Salaam Urban Health
on them.                                         full cost-recovery of drugs in a few Dar         place. The budget gap is filled with         Project’s drug supply experience was
    Ten years later pharmacists are more         es Salaam public dispensaries. The do-           Government and donor contribu-               and is a learning process. An efficient,
involved, visible and in control. They           nor contribution gradually decreased and         tions. Financial sustainability seems
have gained some self-confidence and a           ended in 2000 with that phase of the             possible provided there is continued                                 ...cont’d on page 27 ➠

                                                                                                                                                             Issue No. 28 & 29, 2000
   ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                    27




                          ACCESS




                        Why do the poor pay more?
                        Survey reveals disparity in drug prices
                                 hat effect is an increasingly          ➤ prices of each package size in the na-       importer prices vary between countries.          reverse engineering (a practice for discov-

                         W       globalised economy with tighter
                                 intellectual property systems
                                 having on developing countries’
                                                                            tional currency and then converted to
                                                                            US dollars.
                                                                            In line with the results of other stud-
                                                                                                                       And that import duties and distribution
                                                                                                                       costs, pharmacy margins and local taxes
                                                                                                                       also vary greatly between countries, but
                                                                                                                                                                        ering the manufacturing process of a
                                                                                                                                                                        product starting from the finished prod-
                                                                                                                                                                        uct), as the country’s legislation did not
                        efforts to make essential drugs available       ies reported at the Nairobi Conference         particularly from one developing coun-           provide patent protection for products, the
                        and affordable? A Consumers Interna-            (see page 20), the survey found a very         try to another, so contributing to price         authors state.
                        tional and HAI survey in 1999 addressed         wide variation in retail prices in the coun-   differentials.                                       The report advocates that provisions
                        this crucial question. The survey exam-         tries surveyed. Among its most striking            This wide range in proprietary drug          for compulsory licensing and parallel
                        ined retail prices of 16 drugs in 36            findings were that:                            prices in developing countries (1:4–1:59)        imports should be in all national legisla-
                        countries – 10 advanced economies and           ➤ in some developing countries retail          is shown in the Table, with India having         tion on intellectual property rights as
                        25 developing ones in Africa, Asia and              prices were higher than in developed       the lowest prices for six out of nine dos-       permitted by TRIPS. It states that this will
                        Latin America, plus one from the                    countries. This was the case for 15 out    age forms. Consumers International and           help developing countries ensure regular
                        Commonwealth of Independent States.                 of 18 dosage forms of 11 drugs (those      HAI argue that the Indian situation proves       access to good quality essential drugs at
                            For the study the drugs were grouped            for which comparable data exist);          that competition is possible in the phar-        affordable prices. ❏
                        into three categories according to their        ➤ proprietary brand forms of several of        maceuticals market and that it brings
                        patent status: those still under patent in          the multisource drugs surveyed are the     prices down. They say that India under-
                        some countries; drugs whose patents will            only products available in many of the     scores the need for national policies on         For further information contact: Consumers
                        expire soon or have recently expired;               African countries. This is even though     intellectual property systems with provi-        International, 5th Floor Wisma WIM, 7 Jalan
                        and multisource drugs with several                  low priced generic equivalents are         sions to enable national firms to begin          Abang Haji Openg, Taman Tun Dr. Ismail,
                        companies’ products available in all                                                           production of new drugs as quickly as            60000 Kuala Lumpur, Malaysia. Fax: + 60
                                                                            available in the world market, in coun-
                        the countries. The drugs are all widely                                                        possible. Indian firms could do this by          3 772 61599, e-mail: consint@ciroap.org
                                                                            tries not offering patent protection to
                        prescribed.
                                                                            pharmaceuticals;
                            HAI partners and Consumers Inter-                                                          Price comparison of 8 proprietary brand drugs
                                                                        ➤ survey differences in the retail prices
                        national members visited leading retail
                        pharmacies in the 36 capital cities
                                                                            of proprietary drugs are much wider        in developing countries in the study
                                                                            (range 1:16–1:59), than those for
                        seeking information on the:
                                                                            prices of generic equivalents (range           Generic name           Retail price of 100 units in US$                             Ratio of
                        ➤ availability and retail prices of the pro-        1:7–1:18);                                                            Country       Price        Country              Price        lowest to
                            prietary or brand name product of the       ➤ variations in the retail prices of                                                                                                   highest price
                            16 drugs;                                       multisource drugs in developing coun-                                      Lowest                       Highest
                        ➤ total number of products which in-                tries are much wider than the                  Acyclovir 200mg        Togo          50           Indonesia            371              1:7
                            clude the originator’s brand, branded           variations in the developed countries.         Acyclovir 800mg1       India         94           South Africa         790              1:8
                            generics and generics of each of the            While the study did not analyse the            Atenolol 25mg          India         03           Cameroon             53               1:18
                            16 drugs available in the pharmacy;         sources of price variations, researchers           Ciprofloxacin 500mg    India         15           Mozambique           740              1:49
                        ➤ retail prices of the originator’s brand       suggest that the small difference in prices        Diclofenac 50mg        India         02           Argentina            118              1:59
                            and the package size. Where several         in the industrialised countries may in part        Nifedipine 20mg        India         03           Peru                 96               1:32
                            products of the drug were available,        be due to co-marketing arrangements by             Omeprazole 20mg        Zambia        30           Brazil               477              1:11
                            the prices of the next two best-selling     manufacturers, parallel importing, refer-          Ranitidine 150 mg      India         02           South Africa         116              1:58
                            products in addition to the proprietary     ence pricing and drug pricing policies.            Zidovudine 100mg       Pakistan      81           Argentina            316              1:4
                            brand or top-selling brand.                 Other studies have shown that producer/



                        Dar es Salaam...                                   a visible symbol of development, to             makes evidence-derived outcome               a resource for and in interrelation with
                        cont’d from pg. 26                                 gain people’s confidence and satisfy            measurement difficult.                       other sub-systems that have to be coordi-
                                                                           politicians, but it was not sustainable                                                      nated. For the new drug supply system,
                                                                                                                       ➤ An efficient national Medical Stores
                        reliable and sustainable drug supply sys-          by itself.                                                                                   which developed over nearly 10 years, to
                                                                                                                         Department has proven to be one of
                        tem depends on a variety of internal and        ➤ There was insufficient effort to in-                                                          be sustainable active consolidation is
                                                                                                                         the main pillars for the drug supply
                        external factors, and many components             volve, train, empower and motivate                                                            necessary. New structures and processes
                                                                                                                         system, providing drugs of good
                        and actors determine its success. In ret-         pharmacy staff. To have had phar-                                                             need to be kept alive, to be to imple-
                                                                                                                         quality at affordable prices. Thus ex-
                        rospect we learnt the following lessons:          macy staff proficient in drug supply                                                          mented and to become established, to
                                                                                                                         ternally organized tendering and
                        ➤ Initially there was mainly an external          management from the beginning                  import from overseas could be re-              avoid falling back into old patterns. Ac-
                          materials injection, i.e. provision of          would have been extremely important            placed by local and professional bulk          tive consolidation involves strengthening
                          drugs, which increased their short-             for improving allegiance and coopera-          purchasing, clearing, distribution and         as well as internal and external support.
                          term availability. Human resources,             tion, including early capacity-building        storage of essential drugs.                    This translates into careful monitoring,
                          infrastructure such as pharmacy                 and training. Emphasis needed to be                                                           supportive supervision and continuing
                                                                                                                       ➤ The Tanzanian National Drug Policy             education. A key assumption is a stable
                          premises, and drug supply manage-               placed on improving skills, increas-
                                                                                                                         has been an important tool and frame-          and supportive political environment. ❏
                          ment skills were neglected. The                 ing motivation and changing attitudes.
                                                                                                                         work for the development of a more
                          provision of drugs was important, as            Supportive supervision and monitor-
                                                                                                                         efficient, equitable and sustainable           * Dr Karin Wiedenmayer is a pharmacist at
                                                                          ing as well as continued education are
                                                                                                                         drug supply system for the Dar es              the Swiss Tropical Institute, Socinstrasse 57,
                                                                          important tools.
                                                                                                                         Salaam Project.                                CH-4002, Basle, Switzerland, and Dr
                                                                        ➤ In order to follow-up, monitor and                                                            Deo Mtasiwa is the City Medical Officer of
                                                                          evaluate the quantitative and quali-                                                          Health, Dar es Salaam, United Republic of
                                                                          tative outcome of a high invest-
                                                                                                                       A   TENTATIVE OUTLOOK                            Tanzania.
                                                                          ment drug supply system over 10                 A drug supply system cannot be man-
                                                                                                                                                                        References
                                                                          years, a detailed baseline assessment        aged in an isolated way but needs to be
                                                                                                                                                                        1.    Kanji N, Kilima PM, Munishi GM. Quality of primary
Photo: K. Wiedenmayer




                                                                          with structure, process and outcome          considered as part of a larger socio-                  curative care in Dar es Salaam. Dar es Salaam: Dar es
                                                                          indicators should have been con-             cultural, political and economic context               Salaam Urban Health Project; 1992.
                                                                                                                                                                        2.    Wyss K, Whiting D, Kilima P, Mc Larty DG, Mtasiwa
                                                                          ducted at the beginning of the pro-          and environment. It is also part of an or-             D, Tanner M, Lorenz N. Utilisation of Government and
                                                                          ject. However only some rather               ganization, the supporting health sys-                 private health services in Dar es Salaam. East African
                                                                                                                                                                              Medical Journal 1996; 73:357.
                                                                          randomly and informally collected            tem, from which it cannot be isolated.           3.    World Bank. Better health in Africa. Experiences and
                        Training prescribers in rational use of drugs     information was available, which             Each sub-system, such as drug supply, is               lessons learnt. Washington D.C.: World Bank; 1994.



                        Issue No. 28 & 29, 2000
                              28                                                                                                                          ESSENTIAL DRUGS MONITOR




                                DRUG            INFORMATION




                              Introducing Pakistan’s first Drug
                              Helpline for professionals and patients
                                                                ➢ AYESHA AHMED*                                            Pills, American Hospital Formulary             months in operation showed that 47% of
                                                                                                                           Service, Physician’s Desk Reference, USP       users were health professionals including
                                     roviding independent drug information to health professionals and                     Drug Information, WHO Drug Informa-            doctors, pharmacists and paramedic staff,

                               P     consumers through specially designated drug information centres is a
                                     relatively new concept in Pakistan. Although many countries automati-
                                     cally incorporate such centres in hospitals, in Pakistan they are rare.
                                                                                                                           tion, British National Formulary and
                                                                                                                           Ellenhorne’s Medical Toxicology are
                                                                                                                           available. Information is also gathered
                                                                                                                                                                          and 53% consumers. The most frequently
                                                                                                                                                                          asked questions concern side-effects,
                                                                                                                                                                          availability and cost of medicines, fol-
                              Those that exist, such as at the Aga Khan Medical University Hospital and                    from the electronic discussion groups          lowed by drug dosage regimen, drugs
                              Jinnah Post-Graduate Hospital, Karachi, and Lahore’s Children’s Hospital, are                Essential Drug (E-Drug) and International      of choice, drug interactions and drug use
                              only for use by health professionals. But recently The Network-Association for               Network of Drug Information Centres            during pregnancy. Approximately 95%
                              Rational Use of Medication in Pakistan has established a Drug Information                    (INDICES).                                     of questions are answered by telephone,
                                                                                                                                                                          and the rest receive written replies.
                              Helpline, the first of its kind in the country. Catering to the needs of doctors
                              and patients, it is not hospital based but is run from The Network’s office in               Much in demand
                              Islamabad.                                                                                                                                  Spreading the word
                                                                                                                               Although it is early to assess its con-
                                                                                                                           tribution to rational drug use, the ser-           The Helpline has printed separate pub-
                              Meeting a need                                 support from WHO, it aims to give             vice is catering to the needs of eleven        licity brochures in English and Urdu and
                                                                             adequate, objective and up-to-date            hospitals, both Government- and non            posters in the local Urdu language. Each
                                  As elsewhere, the available sources of                                                   Government-run. Analysis after 12              hospital in Islamabad and Rawalpindi was
                                                                             information on request.
                              drug information for Pakistan’s health
                              professionals, apart from pharmaceutical
                              companies, are the standard pharmacol-         A comprehensive service
                                                                                                                             Ref No.
                              ogy textbooks, and local and international         A pharmacist, trained at the WHO
                              compendia. These are not only cumber-                                                          The Network’s Drug Information Helpline
                                                                             Collaborating Centre for Drug Informa-
                              some but soon become outdated. Busy            tion, The National Poison Centre in
                              physicians have little time to go through                                                      Administrative Record:
                                                                              Penang, Malaysia, runs the Helpline.
                              these sources and may rely                                                                     Requestor (Name):                                       Date:
                                                                                  Consumers and health professionals
                              mostly on industry infor-                                                                      Profession (Please tick the right option):              Time:
                                                                                     access the service by phone, fax,
                              mation about medicines.                                                                        ❏ Doctor       ❏ Pharmacist       ❏ Nurse               Status: ❏ New ❏ Follow up
                                                                                       mail and e-mail. Working hours
                                  Although patient                                         are quite short, 9am–5pm          ❏ Paramedic ❏ Medical/ Pharmacy students                Method of communication:
                              information leaflets                                             Monday to Friday, main-       ❏ Public                                                ❏ Verbal     ❏ Written
                              supplied by the manu-                                             ly due to financial and
                              facturer accompany                                                                             Address of the requestor:
                                                                                                staffing constraints.
                              each medicine, the                                                   The Helpline provides     Tel:
The Network’s Drug Bulletin




                              consumers’ sources of                                            information on drug dos-      Patient Information:
                              information about drugs                                        age, formulations, effects      Age:                                        Diagnosis:
                              are mainly their pre-                                          and adverse reactions, and      Sex:                                        Allergies:
                              scriber and word of                                            probable drug interactions      Weight:                                     Medication being used:
                              mouth. But prescribers                                       with food and with other          Occupation:
                              have little or no time to                                  allopathic medicines used to-       Marital Status:                             Laboratory values:
                              tell people about possible ad-                     gether. The service does not offer any      Additional Information:
                              verse/side-effects, precautions or drug        help with disease diagnosis or with pre-
                              interactions, as there are usually other       scribing medication to consumers, nor           Request:
                              patients waiting. They may also be una-        does it provide information on herbal or        Drug Information:
                              ware of some details if the drug company       homeopathic medicines.
                              does not provide complete information.                                                         ❏ General product information               ❏ Drug interaction (unknown/drug/
                                                                                 Requests from health professionals                                                        laboratory/disease/food)
                              Sales representative may minimise the          and consumers are dealt with in different
                              importance of side-effects and precau-                                                         ❏ Pharmacokinetics/Pharmacology             ❏ Side effects/Adverse effects/
                                                                             ways. Consumers have to supply addi-
                              tions, for example. This creates a situation                                                                                                 Contraindication
                                                                             tional information about their prescribers
                              where there is insufficient information for                                                    ❏   Therapy Evaluation/Drug of choice       ❏ Teratogenecity/Genetic effects
                                                                             and their prescriptions. Requests are
                              the doctor and even less for the consumer.     documented on a standard form (see              ❏   Dosage/Regimen recommendation           ❏ Poisoning/Toxicology
                              In the vast majority of cases people dis-      right) and scheduled on the basis of their      ❏   Pharmaceutical (formulation)            ❏ Pregnancy/Lactation/Infant risks
                              cuss their medicines with others showing       urgency and the available resources – all       ❏   Others                                  ❏ Compatibility/Stability/Administration
                              similar symptoms, leading to abuse of          are answered as quickly as possible. Dif-                                                     (rate/method)
                              medicines and the use of completely            ferent queries about the same drug by
                              inappropriate drugs.                           the same person are recorded as one.            Search Conducted (Source and utility, record specific data):
                                                                             For example: if a request comes in for
                              The Network’s efforts                          misoprostol and the doctor has asked
                                                                                                                             Findings/ Evaluation:
                                                                             for its availability, drug interactions,
                                  Since it became involved in the health
                                                                             contraindications, precautions and side-
                              sector nine years ago, The Network, a
                                                                             effects, staff complete only one form and       Response:
                              not-for-profit organization, has been com-
                                                                             the various categories are marked on it.
                              mitted to protecting consumers from
                              harmful effects of medicines caused by
                              lack of knowledge and misinformation.          Our resources                                   Responder:                      Method of response: Verbal, Written
                              Through its publications, especially the           The Centre uses the latest version of       Date:                           Time:                  Time spent:
                              Drug Bulletin, The Network has been            MICROMEDEX, the standard updated
                              catering to the information needs of health    database. It has the Drug Index and the         Follow Up:                      Additional Comment:
                              professionals and consumers, but on an         poisoning information database, Poison          ❏ Effective
                              individual level there was no system to        Index. In addition, the Australian Pre-         ❏ Required additional help
                              deal with specific requests. The Helpline      scriber, Prescrire International, Drug and      ❏ Unsatisfactory
                              has filled this gap. Started with initial      Therapeutics Bulletin, Worst Pills Best

                                                                                                                                                                                   Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                  29




  DRUG            INFORMATION


contacted separately, with a letter and pro-   Iowa Drug Information Service too.               boost the profile of hospital pharmacists      to form a network of such services, based
motional materials sent to the Medical             Currently our dedicated phone-line           and give them an opportunity to become         within hospitals, and once we have shown
Superintendent or Executive Director.          is sufficient for people calling from within     a more integral part of the health team.       our value nationally, we hope to attract
Doctors and other health staff received        Islamabad and Rawalpindi. But it is in-              Independent and objective drug infor-      the funding to ensure sustainability. ❏
publicity materials at seminars about the      convenient for people calling from               mation is essential for achieving rational
service, which were held at all hospitals.     outside the cities, mainly because it is ex-     drug use. If it is to be effective, this in-   * Ayesha Ahmed is the pharmacist in charge
The Drug Bulletin and our Urdu publica-        pensive to call during the peak daytime          formation has to be tailored to the level      of the Helpline. For further information con-
tion featured articles, as did the national                                                                                                    tact: The Network For Consumer Protection,
                                               hours. A separate toll free telephone line       and specific needs of the enquirer. But this
                                                                                                                                               40-A, Ramzan Plaza, G-9 Markaz,
daily English and Urdu newspapers when         would solve this problem.                        is a complex process. By starting small,       Islamabad, Pakistan. Tel: + 92 51 2296802,
the Helpline was launched.                                                                      with what we had, we have shown that           fax: + 92 51 2291552, e-mail: helpline@
                                               Proving our value                                Helplines can be successful. We intend         best.net.pk
Educational activities
                                                   Since the Helpline started as a small
    The drug information Helpline has          pilot project in Islamabad in November
regular input in The Network’s Drug Bul-       1999, it has proved popular with doctors
letin and the Urdu publication Sarfeen
Aur Sehat. As well as providing articles
on specific drugs, the service also passes
                                               and consumers. Now it is facilitating
                                               several hospitals, including major               UK’s new bulletin fills
                                                                                                patient information gap
                                               Government-run ones. We now believe
on the information it has on drug use          that if information services are based
trends, who is accessing the Helpline and      within hospitals, doctors and patients
the types of requests it is receiving.         could access them quicker. It could also
                                                                                                         or many years the UK’s Con-           Consumers Association decided there
Money matters
    The service’s major constraint is
lack of finance. Eventually, we want
                                                                                                  F      sumers’ Association has been
                                                                                                         providing professionals and
                                                                                                         consumers with impartial in-
                                                                                                                                               was still a dearth of high-quality, impar-
                                                                                                                                               tial information about drugs and medi-
                                                                                                                                               cal treatments designed expressly for
                                                                                                formation about health. Now, as more           patients.
to create a national service, but for                                                           patients want to be involved in the in-            The new information bulletin will
this we need more staff. At present                                                             creasingly complex decisions regarding         cover one topic per leaflet, for example,
answering queries and promoting                                                                 their health care, the Association is intro-   antibiotic resistance or weight loss. It will
our service are the major activities,                                                           ducing a new information service. It will      give background information for the
and one person is sufficient to run                                                             reinterpret the information it gives to        newly diagnosed patient, and advice and
the Centre. But we need to publi-                                                               doctors and pharmacists in its Drug            recommendations that match the “parent”
cise our work in other cities; we                                                               and Therapeutics Bulletin in a new bul-        Drug and Therapeutics Bulletin. Pilot is-
need money to travel to them, and                                                               letin for health care consumers. The           sues were tested with patients and health
more staff to handle the increased                                                              doctor- or pharmacist-supplied leaflet         professionals. The Association hopes lo-
number of queries. We want to open                                                              will be accurate, concise, easy to read        cal health authorities will purchase the
at least 12 hours a day or even be-                                                             and up-to-date.                                bulletin and make it available, free of
come a round-the-clock service.                                                                     The Association acted because al-          charge, in doctors’ surgeries and commu-
Resources and equipment also                                                                    though there is a plethora of health and       nity pharmacies. An electronic version
need to be updated. At present we                                                               medical information available, especially      should follow soon. ❏
have older editions of the core                                                                 on the Internet, many patients do not have
                                                                                                                                               For further information contact: Philip Taylor,
titles and our subscription to                                                                  access to it or cannot find the right infor-   Consumer’s Association: Drug and Therapeu-
MICROMEDEX, one of our major                                                                    mation when they need it. Also, it was         tics Bulletin, 2 Marylebone Road, London
information sources, must be re-                                                                felt that the quality of Internet informa-     NW1 4DF, UK. Tel: + 44 20 71 830 7608,
newed in 2001. Moreover, we want        One of the posters produced by the Service as part of   tion is mixed and can be heavily biased        fax: + 44 20 71 830 7664, e-mail: taylorp@
to improve the service by using the     its publicity campaign                                  towards commercial sources. The                which.co.uk




Transparency in US drug approval system –
a lesson for others?
         t is common practice for manu-        These reviews are referred to as approval        the FDA’s web site, although not all drugs     exempt from public disclosure under the

  I      facturers to selectively make
         clinical trial results of new drugs
         available only as abstracts or in
                                               packages and are available for many
                                               drugs approved since 1997 on the FDA’s
                                               web site at http://www.fda.gov/cder/foi/
                                                                                                go before FDA Advisory Committees.
                                                                                                    Copies of approval packages and Ad-
                                                                                                visory Committee transcripts for drugs
                                                                                                                                               Freedom of Information Act until a drug
                                                                                                                                               is approved.
                                                                                                                                                   The selective publication of clinical
meeting presentations, rather than pub-        nda/index.htm Approval packages typi-            approved prior to 1997 can be obtained         trials by manufacturers can influence the
lishing full length journal articles. This     cally contain pharmacology/toxicology,           from the FDA through a request under           perception of a new drug’s therapeutic
creates a problem for those wanting            biopharmaceutics and pharmacokinetics,           the Freedom of Information Act. Access         value by only making available evidence
complete information. However, it is the       and statistical reviews of the data submit-      to these documents is not limited to US        that is most favorable to the drug. It now
companies’ data, and the release of some       ted in a new drug application. The FDA           citizens and US non-profit organizations       appears necessary to wait until a drug’s
results may have a negative impact on          Medical Officer also writes an overall           are granted a fee waiver when the re-          approval package is publicly available
sales. But even when manufacturers do          assessment of a drug’s safety and efficacy,      quested information is shared with the         from the FDA before independent recom-
give a more complete report, the bounda-       based on the reviews and the clinical            public. Procedures for making a Free-          mendations or formulary decisions can be
ries may be blurred between what is            trials submitted in the application.             dom of Information Act request can be          made about new drugs. Controlled access
science – publication of peer reviewed             Transcripts of FDA Advisory Com-             found at http://www.fda.gov/opacom/            to published clinical trial results by manu-
journal articles – and what is basically       mittees are also valuable in that they can       backgrounders/foiahand.html on the             facturers and the lack of transparency
drug promotion. An independent assess-         reveal members’ concerns about a drug’s          Agency’s web site.                             in the drug approval process in other
ment of the drug becomes impossible.           safety and efficacy. Committee members               Since January 2000, FDA reviews of         countries remain problems. ❏
    A partial solution can be found in the     are outside experts who make recommen-           new drugs are available on the FDA’s web
transparency of the US drug approval           dations to the Agency about a drug’s             site at least one day before Advisory Com-
                                                                                                                                               Source: E-Drug electronic discussion group
process, at least for drugs approved there.    approval that are not always followed.           mittee meetings. About 30% of the drugs
                                                                                                                                               message from Larry D. Sasich, Research
The Freedom of Information Act gives           Meetings are conducted under the Fed-            approved by the FDA go before an Advi-         Analyst, Public Citizen Health Research
public access to Food and Drug Admin-          eral Advisory Committee Act to ensure            sory Committee. Legal hearings have            Group, 1600 20th Street, NW, Washing-
istration (FDA) reviews of the clinical        that the public has access to the workings       been taking place to decide if safety and      ton DC, 20009, USA. Fax: + 1 202-588-
trials and other data submitted by manu-       of the government. Transcripts are found         efficacy data can be considered confi-         7796, e-mail: lsasich@citizen.org, Web Site:
facturers as part of a new drug application.   at http://www.fda.gov/foi/electrr.htm on         dential commercial information that is         www.citizen.org/hrg


Issue No. 28 & 29, 2000
30                                                                                                                     ESSENTIAL DRUGS MONITOR




  DRUG           INFORMATION




Going from strength to strength
– Iran’s Drug and Poison
Information Service
                ➢ SHEKOUFEH NIKFAR, MOHAMMAD ABDOLLAHI,                                   Table 2                                                   dermatological drugs (most-
                        ABDOLMAJID CHERAGHALI*                                            Distribution of drug-related questions according to       ly drugs used for acne
                                                                                          anatomical therapeutic chemical classification system     and alopecia), respiratory
                                                                                          from February 1997 to January 2000
       harmacotherapy has become increasingly complex, as patients receive                                                                          drugs (mostly antiasthmatic

 P     more and more drugs to manage their diseases. New prescription drugs
       are being introduced at a bewildering rate1,2,3, and people hear of them
       through the media, and increasingly through Internet. Patients request
                                                                                             Drug class


                                                                                             Central nervous system
                                                                                                                              Number


                                                                                                                              6386
                                                                                                                                       Frequency
                                                                                                                                          (%)

                                                                                                                                           20
                                                                                                                                                    agents). There are also ques-
                                                                                                                                                    tions concerning drugs used
                                                                                                                                                    for specific disease groups
these drugs before their doctors have a chance to build their knowledge base                                                                        like hepatitis, cancer, immune
                                                                                             Gastrointestinal system          4790         15       disease, coagulation factors
on them. Advertising has also increased demand for non prescription and herbal               Systemic anti-infectives         4151         13
                                                                                                                                                    deficiency and thalacemia.
drugs, nutritional therapies and even homeopathic remedies. Studies showed                   Systemic hormonal preparations   3832         12
                                                                                                                                                        The references we use
that drug- and poison-related problems existed in the Islamic Republic of                    Cardiovascular system            3831         12
                                                                                             Genitourinary system             3193         10
                                                                                                                                                    most are the DRUGDEX
Iran, as in many countries, and the lack of a drug information centre was                                                                           (used in 48.9% of queries),
                                                                                             Dermatological system            1916          6
evident. To go some way to meeting the needs of health professionals and                     Respiratory system               1914          6       POISINDEX (16%), TOMES
consumers4, we opened the first Drug and Poison Information Centre in Tehran,                Antineoplastic/                                        (8%) and EMERGINDEX
in February 1997. Three and a half years of hard work later, what have                         immunosuppressive drugs          957         3       (7%) databases. Among our
we achieved?                                                                                 Blood and blood-forming organs     319         1       textbooks Briggs’ Drugs
                                                                                             Various                            642         2       in Pregnancy and Lacta-
    The Centre has 10 staff, two doctors,   Fast, efficient and                                                                                     tion is used most often. Other
two pharmacists and the rest are special-   increasingly popular                                                                                    frequently used textbooks
ists in pharmacology and toxicology.            We analysed 31,931 enquiries to as-       Significantly 10% of the patients contact-     were Martindale’s The Extra Pharma-
Conveniently located in the city centre,    sess the type of users, questions asked and   ing the Centre said they did so because        copoeia, followed by Kathzung’s Basic
we open from 8 a.m. to 8 p.m. Users can     references used between February 1997         their doctor or pharmacist had failed to       and Clinical Pharmacology, Merck
leave a message on the answer machine       and January 2000. Most questions were         provide any information about the uses         Manual, Harrison’s Principles of
after working hours, or submit queries by   answered verbally (85%), 3% were an-          and effects of prescribed medications.         Internal Medicine, American Hospital
post or e-mail. We answer requests by       swered only in writing and 12% were           Forty percent considered the information       Formulary Service Drug Information
phone or in writing. Staff complete a       answered verbally and followed up with        provided to be unclear or in some way          Source and Ellenhorn’s Medical Toxi-
standard request form, covering: name,      a written response. Ninety percent of the     inadequate, and 50% wanted a second            cology. The bibliographic databases of
address, occupation, education, patient     questions took less than 15 minutes to        opinion, to verify the accuracy of infor-      IOWA Drug Information, Medline and
history, the question, category of ques-    answer, while 10% took more than 15           mation provided by the physician or            useful Internet sites are also used
tion, the answer and the references used.   minutes, up to a maximum of two days.         pharmacist.                                    regularly to search medical literature
The staff member also records age,          The number of enquiries rose from 6,500           Table 2 gives a breakdown of drug-         (Table 3).
weight, sex, diagnosis, allergies and cur-  in our first year to 16,898 between           related questions according to anatomi-
rent medications, together with any other   February 1999 and January 2000. The           cal therapeutic classification. Questions     More than an
relevant details of the conversation. The   number and type of questions received         about drugs acting on the central nervous     enquiry service
request form is countersigned by the        by the Centre are given in Table 1. The       system (mostly antidepressants and
                                                                                          anticonvulsants) were the most common,            Drug and poisoning information re-
supervisor who reviews the responses.       majority concerned problems involving
                                                                                          followed by requests concerning               quests take up most time. But in our
If we suspect that a caller has had an      therapeutic use (indication and efficacy),
                                                                                          gastrointestinal drugs (mostly acid low-      efforts to educate and promote rational
adverse reaction to medication, we re-      poisoning, pregnancy and lactation, and
                                                                                          ering agents), systemic anti-infectives       use of drugs we do far more than wait for
port the incident to the National Adverse   adverse effects. Among poisoning cases
                                                                                          (mostly fluoroquinolones, cephalosporins      questions to come to us. As Table 4 shows
Drug Reaction Centre, with which we         most enquiries concerned drugs (70%),
                                                                                          and penicillins), systemic hormonal           the Centre participates in pharmacy and
collaborate very closely.                   followed by other chemicals (20%) and
                                                                                          preparations (mostly sex and thyroid hor-     therapeutic committees; gives workshops,
    We are rigorous about quality, and an   herbals or natural toxins (10%).
                                                                                          mones, then antidiabetics), cardiovascular    seminars and lectures as part of its
internal committee at the Centre reviews        Physicians (26%), pharmacists (25%)
                                                                                          drugs (mostly ß-adrenoceptor blockers         training and education programme;
response forms regularly, looking at the    and patients or their relatives (25%) were
                                            the most frequent users, while nurses         and antihypertensives), drugs affecting       produces information newsletters,
references used, and the clarity, accuracy                                                                                              pamphlets and review articles; conducts
                                            (8%), dentists (6%) and other health pro-     the genitourinary system (mostly drugs
and completeness of answers.                                                              for impotence and erectile dysfunctions),     literature searches; provides mass media
                                            fessionals (5%) use us to a lesser extent.
                                                                 Physicians mainly
Table 1                                                          asked about drug dos-    Table 3
Categories of enquiries at the Drug and Poison Information       age and therapeutic      The most frequently used references at the Drug and Poison Information Centre
Centre from February 1997 to January 2000 (n=31931)              use, while specialists   from February 1997 to January 2000 (n=31931)
                                                                 were interested in the
   Enquiries                         Number Frequency (%)                                    Reference name                                             Number Frequency (%)
                                                                 comparative efficacy
   Therapeutic use                    5109          16           and toxicity of drugs,      DRUGDEX Micromedex international health care series        15615         48.9
   Poisoning                          4470          14           particularly new            POISINDEX Micromedex international health care series       5109         16
   Pregnancy and lactation            3832          12           ones. Most pharma-          TOMES Micromedex international health care series           2554          8
   Adverse effects                    3512          11           cists wanted to know        EMERGINDEX Micromedex international health care series      2235          7
   Dosage                             3193          10           about formulations,         Briggs Drugs in pregnancy and lactation                     1596          5
   Drug abuse                         3098            9.7        interactions, identi-       Martindale The extra pharmacopoeia                           734          2.3
   Therapeutic comparative efficacy   2554            8          fication of foreign         Kathzung Basic and clinical pharmacology                     639          2
   Interaction                        2235            7                                      Merck manual                                                 639          2
                                                                 products and sub-
   Substitution                       1277            4                                      Harrison Principles of internal medicine                     638          2
                                                                 stitution. Nurses
   Precautions                         958            3                                      AHFS Drug information source                                 638          2
   Identification of foreign product   639            2
                                                                 commonly asked us
                                                                                             Ellenhorn Medical toxicology                                 447          1.4
   Contraindications                   639            2          about pharmaco-             MEDLINE                                                      416          1.3
   Metabolism                          319            1          kinetics, dosage            IOWA drug information services                               319          1
   Pharmaceutical compatibility          96           0.3        and compatibility of        Others                                                       352          1.1
                                                                 intravenous drugs.

                                                                                                                                                  Issue No. 28 & 29, 2000
 ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                                               31




                                               DRUG           INFORMATION


                                                                                                              As our drug and poison         sources for patients. We are also consid-       Our analysis of queries has shown that
                                                                                                          information pamphlets are so       ering having a computer-based system            too little of this exists in Iran and under-
                                                                                                          popular, the Centre has cre-       to assist in analysing information, and         lines the Centre’s crucial role in the health
                                                                                                          ated a subscription service,       documenting the Centre’s activities and         care system and the community. ❏
                                                                                                          which includes over 20,000         effectiveness.
                                                                                                          health professionals. They             Staff believe they could be even more
                                                                                                          regularly receive literature       effective if health professionals’ training     * Dr Shekoufeh Nikfar, is Director of the Drug
                                                                                                                                                                                             and Poison Information Centre, Tehran, Dr
                                                                                                          promoting rational drug use,       and continuing education covered the role
                                                                                                                                                                                             Mohammad Abdollahi, is Associate Profes-
Drug and Poison Information Centre, Tehran




                                                                                                          often based on our most            and use of drug information centres. We
                                                                                                                                                                                             sor of Pharmacology and Toxicology, Faculty
                                                                                                          interesting queries.               also want to see more training in applied
                                                                                                                                                                                             of Pharmacy, Tehran University of Medical
                                                                                                              We want as many Irani-         toxicology, to reduce the large number of       Sciences, and Scientific Consultant to the
                                                                                                          ans as possible to have            poisoning queries we receive.                   Drug and Poison Information Centre, Tehran,
                                                                                                          access to drug information,            Our work with the public is very im-        and Dr Abdolmajid Cheraghali is Associate
                                                                                                          not only those living in the       portant, particularly given our findings on     Professor of Pharmacology and Toxicology,
                                                                                                          capital. So we have estab-         the lack of information patients receive        Faculty of Medicine, Baghiyatallah Univer-
                                                                                                          lished new drug and poison         about their prescribed medicines, and           sity of Medical Sciences, and Scientific
                                                                                                          information centres – more         people’s increased exposure to advertise-       Consultant to the Drug and Poison Informa-
                                                                    Drug and Poison Information Centres than 15 to date – all with           ments and media-provided information.           tion Centre, Tehran, Iran. For further
                                             New drug and poison information centres are being set up     access to a computer and           Correct, unbiased and practical drug and        information contact: Drug and Poison Infor-
                                             throughout Iran                                              references (see map). The          poison information is one of the best ways      mation Centre, 2nd floor, Under-Secretary of
                                                                                                          Tehran Centre supports them        to neutralise the effect of drug promotion      Food and Drugs, Ministry of Health, Fakhr-E-
                                             information to help increase rational use       by providing reference materials and            and reduce drug-related adverse effects.        Razi Street, Engheleb Avenue, Tehran-Iran.
                                             of drugs; and reports to the Adverse Drug       funds.
                                                                                                                                                                                                                        References
                                             Reaction Centre. As the Service’s popu-             After our first assessment of the Cen-      Table 4
                                                                                                                                                                                                                        1.   Johnson JA, Bootman JL.
                                             larity has grown so too has the variety of      tre we are optimistic about its future.         Percentage of time spent on Drug and Poison Information
                                                                                                                                                                                                                             Drug-related morbidity and
                                             organizations we assist.                        Questionnaires distributed to health pro-       Centre activities from February 1997 to January 2000                            mortality. Arch Intern Med
                                                                                                                                                                                                                             1995;155:1949–1956.
                                                 The Centre tries to ensure that the lit-    fessionals during seminars showed that
                                                                                                                                                Activity                                          Frequency (%)         2.   Fontanarosa PB, Lundberg
                                             erature it produces meets the needs of          they thought our service has an impact                                                                                          GD. Alternative medicine
                                             users. So, when we do quality checks on         on prescribing practice, and in most cases         Providing drug and poisoning information                30                   meets science. JAMA 1998;
                                             our responses we also assess the need for       users were satisfied with their consulta-                                                                                       20:1615–22.
                                                                                                                                                Producing newsletters and pamphlets                     14
                                             education materials on particular topics.       tion. The increased rate of enquiries and          Providing seminars and giving lectures                  10              3.   Rodriguez C, Arnau JM, Vidal
                                                                                                                                                                                                                             X, Laporte JR. Therapeutic
                                             For example, we were receiving questions        users are other positive indicators.               Reporting to the Adverse Drug Reaction Centre           10                   consultation: a necessary ad-
                                             from young men about the effects of ana-            Now we want to build on success.               Preparing review articles                                9                   junct to independent drug
                                                                                                                                                Providing workshops, training and education              8                   information. Br J Clin Pharma-
                                             bolic drugs that might be used for body         The Centre is preparing more reference             Establishing new drug and poison information centres     7                   col 1993;l 35:46–50.
                                             building. We immediately increased our          materials for health professionals and             Participating in pharmacy and therapeutic committees     5              4.   Hemminki E, Herxheimer A.
                                             dissemination of information on this sub-       expanding its e-mailing of informa-                Conducting literature searches                           4                   Should drug information be an
                                                                                                                                                                                                                             integral part of health care? J
                                             ject in seminars, the mass media and our        tion on specific diseases to patients. We          Providing mass media information                         3                   R Coll Physicians Lond 1996;
                                             newsletters.                                    are doing more evaluation of Internet                                                                                           30:104–6.




                                               RESEARCH



                                             Burkina Faso: study shows value of                                                                                                              Only by correlating prescriptions to pa-
                                                                                                                                                                                             tients’ diagnoses was it possible to detect
                                                                                                                                                                                             problems of false dosage and contra-

                                             qualitative monitoring                                                                                                                          indications, and to identify certain risk
                                                                                                                                                                                             groups. So while quantitative drug use
                                                                                                                                                                                             indicators have proved very useful for a
                                                                                                                                                                                             rapid and economic assessment of gen-
                                                     hile prescribing practices have        drugs list, but only 59.3% of prescriptions      patients received no information on how

                                             W
                                                                                                                                                                                             eral drug use habits, in-depth studies
                                                     been studied in various develop-       conformed to standard treatment guide-           long a prescribed drug had to be taken.         may be necessary from time to time. Ad-
                                                     ing countries, most research has       lines. In all other prescriptions at least one   Prescribing was similar in both the ob-         ditionally this methodology allowed the
                                                     limited evaluation to numerical        drug was not indicated or the dosage was         served and the unobserved consultations.        identification of special risk issues and
                                             analysis, such as the number of drugs pre-     wrong. Errors in dosage occurred signifi-            The study concludes that a significant      risk groups, so helping to determine the
                                             scribed or the percentage of prescriptions     cantly more often in children under the          proportion of patients probably received        focus of further interventions. ❏
                                             containing an antibiotic. But a study          age of five, mostly in terms of dangerous        ineffective or even harmful prescriptions,
                                             carried out in Burkina Faso1 used both         overdosing. Seven out of 21 pregnant             although the interpretation of quantitative     Reference
                                                                                                                                                                                             1.    Krause G et al. Rationality of drug prescriptions in rural
                                             qualitative and quantitative indicators to     women received drugs contraindicated in          indicators alone would have led to a posi-            health centres in Burkina Faso. Health Policy and
                                             investigate the rationality of drug pre-       pregnancy. In two-thirds of all cases the        tive evaluation of prescribing practices.             Planning 1999;14(3):291-298.
                                             scriptions at outpatient consultations. The
                                             study results demonstrate the importance
                                             of a multifaceted research approach, and
                                             add to the evidence that greater efforts
                                             must be made to improve prescribing
                                             practices globally.
                                                                                            Science shopping in the Netherlands
                                                 Specially trained medical students and              move to bring science out of the        receives many of its research questions         drug analyses are also possible. In recent
                                             nurses observed a total of 313 outpatient
                                             consultations in nine health centres in
                                             three rural districts. Data on 2,815 drug
                                                                                             A       “ivory tower” and into the serv-
                                                                                                     ice of a wider public has been
                                                                                                     proving very successful in the
                                                                                                                                             from patients’ associations, consumer
                                                                                                                                             organizations and women’s groups.
                                                                                                                                                 When a question comes in, the Sci-
                                                                                                                                                                                             years many questions have been asked
                                                                                                                                                                                             about the use of drugs for psychiatric dis-
                                                                                                                                                                                             orders and about women’s health issues.
                                             prescriptions were also analysed. These        Netherlands. The idea for Science Shops          ence Shop looks for a staff member in the          As well as collaborating with the other
                                             had been copied from patient registers         originated in the 1970s, and today there         Pharmacy Faculty whose work ties in to          research information centres at Utrecht
                                             two months before observation began, in        are more than 30 such research informa-          the topic, which generally concerns phar-       University, the Science Shop for Medi-
                                             order to compare prescribing habits in         tion centres, affiliated with 11 universities    macotherapy or pharmacoepidemiology.            cines often works with Groningen
                                             observed and unobserved consultations.         and covering a wide field – from health          Then, under supervision, a student does         University’s Medicines Shop and the
                                                 During the two-week study period 366       to literature. Financed by the universi-         a literature review and receives study          country’s seven Health Shops. ❏
                                             prescriptions for 793 drugs were given         ties, the Shops may work free of charge          points for the work. The study is usually
                                             out and an average of 2.3 drugs was            for non profit social organizations need-        written up as a short report or brochure,       For further information contact: Science Shop
                                             prescribed per visit. A total of 33.1% of      ing help with community-based research.          available from the Shop for a nominal           for Medicines, Sorbonnelaan 16, Postbus
                                             prescriptions contained antibiotics and        One of them is the Science Shop for              charge. While a literature review is usu-       80082, 3508 TB Utrecht, the Netherlands.
                                             24.6% contained injections. Of the drugs       Medicines attached to Utrecht Uni-               ally what is required, other types of           Tel: + 31 30 253 7309, fax: + 31 30 253
                                             prescribed, 88.0% were on the essential        versity’s Faculty of Pharmacy, which             research, such as surveys, interviews and       9166, e-mail: wewi@far.ruu.nl


                                             Issue No. 28 & 29, 2000
32                                                                                                                                         ESSENTIAL DRUGS MONITOR




  COURSES                    &      MEETINGS


Lebanon hosts                                       Community-based health education and health                                                             Diploma in Drug
drug policy seminar                                 promotion course                                                                                        Evaluation and
    The many issues surrounding drug pro-               A 10-week course to update managers, project and field staff on new developments
                                                                                                                                                            Pharmaceutical Sciences
curement, production, regulation and use,           in health education and health promotion will run from 30th April 2001 at Leeds Metro-                      Today’s potent drugs, combined
and how best to develop, implement and              politan University, UK. The course provides skills in research, planning, management                    with the complex issues of their produc-
evaluate a national drug policy were hotly          and evaluation of programme’s education and promotion components. Its flexible struc-                   tion and use, have created a growing
debated at a seminar held in Lebanon in             ture allows participants to follow a topic of particular interest, and the chance to apply
                                                                                                                                                            need for evaluation of their safety and
October 2000. The event was organized               their new skills to a problem from their own work-setting.
                                                                                                                                                            efficacy.
by Boston University’s Centre for Interna-              Applicants should have field experience/training in a subject area relevant to health
                                                                                                                                                                For such evaluation wide-ranging ex-
tional Health and the Inter-Ministerial             promotion and a good working knowledge of English. The fee for academic tuition,
Council for Health Reform in Lebanon, in            course materials and field visits is £3600. In addition students will have to pay travel,               pertise is required in the areas of chemistry,
collaboration with WHO.                             subsistence and accommodation expenses.                                                                 pharmaceutics, pharmacology and toxi-
    The seminar’s workshop format com-                                                                                                                      cology, clinical medicine, and legal and
bined lectures, in-depth discussion of case         For further information contact: Overseas Admissions Tutor, Health Education, Queens Square House,      ethical considerations.
                                                    Leeds Metropolitan University, Calverley Street, Leeds, LS1 3HE, UK. Tel: + 44 113 2831915, fax: + 44       The new Graduate Diploma in
studies and small-group exercises, plus
                                                    113 2831916, e-mail: health-promotion@lmu.ac.uk or john@hubley.co.uk                                    Drug Evaluation and Pharmaceutical
several field visits to health facilities and
community pharmacies. The meeting at-                                                                                                                       Sciences offered by the University of
tracted policy-makers and senior managers                                                      ◆       ◆     ◆                                              Melbourne, Australia, offers a systematic
responsible for pharmaceutical systems                                                                                                                      overview of these areas and how they
in developing and transitional countries,           Zimbabwe hosts rational use course                                                                      affect drug evaluation. The course is
and senior officials of funding agencies                                                                                                                    aimed at pharmacists, research nurses,
throughout the region.                                  The next INRUD/MSH/EDM course on Promoting Rational Drug Use will be held at                        scientists and those involved in regulatory
    Previous seminars have been held                Victoria Falls, Zimbabwe, from 26 August – 8 September 2001. Topics will include                        affairs.
successfully in Africa, India and the USA.          identifying drug use problems, developing and evaluating interventions and developing
                                                    public and prescriber educational materials and campaigns. This highly participatory
For information on future seminars contact: Dr      course is intended for physicians, pharmacists, health programme managers, policy-                      For further information contact: Mrs Nicola Cash,
Richard Laing, Associate Professor of Interna-      makers, researchers and others interested in improving the use of drugs.                                Drug Evaluation Unit, Austin and Repatriation
tional Health, Boston University School of Public                                                                                                           Medical Centre, Studley Road, Heidelberg
Health, 715 Albany St, T4W, Boston MA 02118,        For further information contact: PRDU course, NDTPAC, Directorate of Pharmacy Services, Ministry of     Vic 3084, Australia. Tel: + 61 3 9496 3420,
USA. Tel: + 617 414-1444, fax: + 617 638-4476,      Health and Child Welfare, Box CY924, Harare, Zimbabwe. Tel: + 263 4 730970 or + 263 4 795353,           fax: + 61 3 9459 3510, e-mail: nicola@
e-mail: richardl@bu.edu                             e-mail: inrudzim@healthnet.zw                                                                           austin.unimelb.edu.au

                 ◆     ◆     ◆                                                                 ◆       ◆    ◆                                                                ◆     ◆     ◆



  NETSCAN


Catch up on the                                     developing world, and the Lancet is ap-                Children and medicines                           links are provided to other Web sites
Australian Prescriber                               pealing for support in its effort to make                                                               containing full texts of the legislation.
                                                    knowledge accessible to all members of                    The United States Pharmacopoeia has
    For the first time the Internet version of      the international health community.                    posted “References for Children and              You can query a database by selecting a country,
                                                                                                           Medicines” with abstracts on its Web site:       a subject, a volume, and by looking for a specific
the journal Australian Prescriber is avail-
                                                                                                           www.usp.org This is a 47-page document           keyword. Check out the site at: http://www.
able in PDF format, with Acrobat reader                              ◆    ◆     ◆                          with references primarily relating to be-        who.int/idhl
software provided. Back issues of the
journal (from 1994) are also available                                                                     haviour, ethics and rates of use. Send
on the Web site at http://www.                      SATELLIFE Information                                  suggestions for additions to Patricia J. Bush,                    ◆     ◆     ◆
australianprescriber.com                            Services’ new automatic                                e-mail: pjb@usp.org
                                                    response                                                                                                HIF-net at WHO
                 ◆     ◆     ◆                                                                                             ◆    ◆     ◆
                                                        There is a new and easy way to                                                                          HIF-net at WHO is an e-mail discus-
                                                    learn about the free information services                                                               sion list for people who want to improve
Read INRUD News                                     that SATELLIFE makes available to                      Ordering WHO books on                            access to reliable information for health
on the Web                                          health professionals, particularly those               pharmaceuticals?                                 workers in developing and transitional
                                                    in the developing world. Send a request                                                                 countries.
    INRUD News, the twice-yearly journal            to <autoinfo@usa.healthnet.org> insert-                    Check out WHO priced publications                To join, send an email message to
of the International Network for Rational           ing no text in the body of your message                on pharmaceuticals at: http://www.who.           the list moderator at: INASP_Health@
Use of Drugs (INRUD) is now available on            and leaving the subject line blank. You                int/dsa/cat98/phar8htm                           compuserve.com
the Web. Published twice a year, over               will soon receive details of SATELLIFE’s                                                                    In the body of the message, say you
3,000 copies of the journal are distributed         services.                                                                                               want to participate in HIF-net at WHO and
free of charge worldwide. Contents include                                                                                 ◆    ◆     ◆
                                                                                                                                                            add a few lines about your professional
updates on INRUD global activities, news
                                                                                                                                                            interest in health information. This will be
from country and support groups, meet-              For further information see page 6. You can also
                                                    visit SATELLIFE on the Web at: http://www.
                                                                                                           No Free Lunch                                    used as your HIF Participant Profile. Your
ing and workshop reports, research briefs,
                                                    healthnet.org                                                                                           name will be added to the list and the
and references to articles on rational use                                                                      No Free Lunch, which is dedicated to
                                                                                                                                                            WHO server will automatically send you
of drugs.                                                                                                  evidence-based health care, has created
                                                                                                                                                            a welcome message with details on how
                                                                     ◆    ◆     ◆                          a listserve, called nofreelunchserve. The
You can subscribe to INRUD News, and read                                                                                                                   to participate.
                                                                                                           list is intended to serve as a forum for the
current and previous issues by clicking on the                                                                                                                  For an information sheet on HIF-net at
                                                    Drug Price Indicator Guide                             exchange of ideas and information.
newsletter icon at http://www.msh.org/inrud                                                                                                                 WHO, send an e-mail to: majordomo@
                                                    updated                                                Subscribe at: http://www.nofreelunchserve@
                                                                                                                                                            who.int leave the subject line blank, and
                 ◆     ◆     ◆                                                                             pairlist.net                                     in the message-box type: info hif-net
                                                        The International Drug Price Indicator                                                                  Messages to the whole list should be
                                                    Guide, available on Management Sci-                                                                     sent to hif-net@who.int
Lancet’s electronic research                        ences for Health Manager’s Electronic                                  ◆    ◆     ◆                         Health Information Forum (HIF) is run
archive                                             Resource Centre Web site at: http//                                                                     as an activity of the INASP-Health Pro-
    The Lancet has launched an experimen-
                                                    erc.msh.org has been updated. Data                     International Digest of                          gramme, a cooperative network of partners
                                                    for the 1996, 1998, 1999 and 2000 edi-                 Health Legislation on-line                       which aims to improve global access to
tal electronic research archive (ERA) in            tions are on line. Search capabilities have                                                             information and knowledge.
international health. This self-archive will        also been improved, and new features                   database
be owned by authors and administered by
                                                    added.                                                                                                  Contact: Dr Neil Pakenham-Walsh, Programme
the Lancet. Access will be unrestricted                                                                        The International Digest of Health Leg-
                                                                                                                                                            Manager, INASP-Health, 27 Park End Street,
through the ERA Web site: http://www.                                                                      islation contains a selection of national and
                                                                                                                                                            Oxford OX1 1HU, UK. E-mail: INASP_Health@
thelancet.com/newlancet/eprint                      To obtain a print version of the 1999 Guide con-       international health legislation, mainly of-
                                                                                                                                                            compuserve.com
    The objective is to create a searchable         tact: the MSH Bookstore. Fax: + 1 617-524-2825,        ficial publications and other documents
electronic public library of research in            e-mail: bookstore@msh.org                              forwarded by WHO Member States. Some             Web site: http://www.inasp.org.uk
international health. It is hoped to cover                                                                 texts are summarised, while only the titles
all issues relevant to medicine in the                               ◆    ◆     ◆                          are given for others, but where possible                          ◆     ◆     ◆

                                                                                                                                                                      Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                            33




  NETSCAN


Now HIV/AIDS information                           be viewed and downloaded.                         Pharm-policy                                      not yet widely available. If people have a
                                                       Among recent highlights are the                                                                 permanent e-mail address, but only spo-
in French                                          addition of Operational Principles for
                                                                                                     e-discussion group                                radic access to the World Wide Web, they
    The SAFCO (SIDA en Afrique du                  Good Pharmaceutical Procurement (see                   Discussions in this group cover phar-        only need to fill out a BioMail form once
Centre et de l’Ouest) network has been             below) and Quality Assurance of Pharma-           maceutical policies, particularly those           and they will receive new references from
set up to encourage discussion and the             ceuticals. A Compendium of Guidelines             involving intellectual property, technology       Medline continually.
electronic exchange of information on is-          and Related Materials. Volume 2. Good             transfer and pricing. Anything significant
                                                   Manufacturing Practices and Inspection.                                                             Find out more at: http://biomail.sourceforge.net/
sues related to HIV or AIDS in francophone                                                           gets on this discussion group within 24           biomail/
Africa. To subscribe send a message                The WHO Medicines Strategy: Frame-                hours: http://lists.essential.org/mailman/
to: safco@hivnet.ch (see page 3 for more           work for Action in Essential Drugs and            listinfo/pharm-policy                                 Links to other free alert sites:
details).                                          Medicines Policy 2000–2003 is now
                                                                                                                                                           Pubcrawler is another Medline alert
                                                   available electronically, as is the docu-
                                                                                                                     ◆     ◆    ◆                      service, available through the Department
                                                   ment Essential Drugs used in the Care of
                 ◆    ◆     ◆                                                                                                                          of Genetics, Trinity College, Dublin,
                                                   People Living with HIV: Sources and Prices.
                                                                                                                                                       Ireland: http://www.pubcrawler.ie
                                                   Some documents in EDM’s Health Econom-            New Medline search tool                               PubMed Query tool: Biotechnology
What’s new on                                      ics and Research Series can also be
                                                                                                                                                       Computing Facility, Arizona Research
EDM’s homepage?                                    downloaded.                                          BioMail periodically does a user-
                                                       The complete English, French and                                                                Laboratories, USA, at: http://bcf.arl.
                                                                                                     customised Medline search and sends all
                                                   Spanish versions of the Monitor (from                                                               arizona.edu/query/add.html
     The Department of Essential Drugs and                                                           matching articles recently added to
Medicines Policy’s homepage is continu-            number 23 onwards) can be found in                Medline to the users’ e-mail address. Medi-           JADE: also a Medline alert service, The
ing to expand and become more user                 PDF format.                                       cal researchers and biologists wanting            National Center for Emergency Medicine
friendly. As well as introducing the essen-                                                          regular updates from journal articles will        Informatics in the USA: http://biodigital.
                                                   Check us out at: http://www.who.int/medicines                                                       org/jade/
tial drugs concept, national drug policies,                                                          benefit from the service, which is free of
and the work of WHO and EDM, many                                                                    charge. It will be particularly useful for
more of the Department’s documents can                             ◆     ◆    ◆                      countries where access to the Internet is                          ◆     ◆     ◆



  PUBLISHED                       LATELY


                                                                                                     Référentiel pour l’harmonisation des procédures d’enregistrement des
                                              Important                                              médicaments essentiels génériques dans les pays de la zone franc et
                                                                                                     pays associés, (Pharmaceutical Sector Collaboration between CFA and
                          The Department of Essential Drugs and Medicines                            Associated Countries), World Health Organization, WHO/EDM/DAP/
                          Policy cannot supply the publications reviewed on                          99.2, 1999, 25 p.
                          these pages unless stated otherwise.
                                                                                                         This guide on harmonization of registration procedures is intended to facilitate the intro-
                            Please write to the address given at the end of                          duction of essential drugs on to the markets of Communauté financière africaine (CFA) and
                            each item.                                                               associated countries, and thus improve the availability and affordability of pharmaceuticals.
                                                                                                     The guidelines, adopted at a seminar in Ouagadougou in February 1999, cover generic drug
                                                                                                     registration and marketing authorisation.

Intellectual Property Rights, the WTO and Developing Countries. The                                  Available, free of charge, from: Department of Essential Drugs and Medicines Policy, World
TRIPS Agreement and Policy Options, C.M. Correa, 2000, 254 p.                                        Health Organization, 1211 Geneva 27, Switzerland.

    The structure of international trade is        exploitation of their natural resources and
being fundamentally altered by the various         welfare effects. The book uses Latin Ameri-
agreements which the World Trade Organi-           can and Caribbean experience to illustrate the    HIV Testing: A Practical Approach, Healthlink Worldwide, 1999, 48 p.
zation polices. This book cuts through the         problems that have arisen with implementing
sometimes daunting technicalities of one of        TRIPS.                                                HIV testing is an essential part of all HIV   and surveillance; and implementing blood
the most important of these agreements, that           Throughout, Correa indicates concrete         prevention and care programmes, to ensure         screening programmes.
dealing with intellectual property rights. The     options available at national level to imple-     safe blood supplies and determine HIV sta-             In addition, the publication provides ex-
publication clearly explains what the Agree-       ment the TRIPS Agreement’s provisions in a        tus. And appropriate counselling, education,      amples of programmes in Africa, Asia and
ment on Trade-Related Aspects of Intellectual      manner consistent with development objec-         care and follow-up support are an essential       Latin America, and experiences from people
Property Rights (TRIPS) is about and its main                                                        part of any HIV testing programme.                who have had HIV tests. A useful resource
                                                   tives and public policy concerns. (See also
provisions.                                                                                              HIV testing: a practical approach pro-        list and detailed technical information on the
                                                   page 36).
    The author is particularly concerned to                                                          vides clear information for policy-makers,        characteristics of some of the most commonly
explore the Agreement’s implications for                                                             planners, and health personnel involved in        used tests are also given.
developing countries. These relate to the          Available from: Zed Books, 7 Cynthia Street,      counselling and HIV testing. An update of the
future of local research and development, ac-      London N1 9JF, UK. Price: £16.95, plus £2.50      1994 publication, Practical issues in HIV test-   Available from: Healthlink Worldwide,
cess to advanced technology, commercial            postage and packing.                              ing, it reflects recent developments, and         Cityside, 40 Adler Street, London E1 1EE, UK.
                                                                                                     lessons learned over the last six years. Topics   E-mail: publications@healthlink.org.uk
                                                                                                     covered include: considerations before be-        Price: £7.50/US$15. Single copies are free
                                                                                                     ginning an HIV testing programme; tech-           of charge to indigenous organizations in
Handbook on Antimicrobial                          Operational Principles for Good                   nical aspects of testing, testing individuals     developing countries.
Therapy, (revised edition), The                    Pharmaceutical Procurement,
Medical Letter on Drugs and                        Interagency Guidelines, World
Therapeutics, 1998, 205 p.                         Health Organization, WHO/EDM/
                                                   PAR/99.5, 2000, 24 p.                             Counterfeit and Substandard Drugs in Myanmar and Viet Nam, World
    This comprehensive handbook on
                                                                                                     Health Organization, EDM Research Series No. 29, WHO/EDM/QSM/
antibacterials, antifungal and antiviral drugs         Pharmaceutical procurement is a complex       99.3, 1999, 55 p.
includes first-choice and alternative drugs for    process and problems are common. This docu-
every indication, doses and adverse effects.                                                             This report presents the results of two studies, done in Myanmar and Viet Nam, to obtain
                                                   ment from the Interagency Pharmaceutical
In addition there are chapters on the safety of                                                      independent information on the counterfeit drugs problem, and so help to develop measures
                                                   Procurement Group sets out four strategic ob-
antimicrobial drugs in pregnancy, advice for                                                         against counterfeiting. The research study involved collecting background information on the
                                                   jectives and 12 operational principles for good
travellers and drugs for HIV infections. The                                                         status of drug regulation and also samples of 500 products, which were subjected to laboratory
non profit publication also includes price lists   procurement. These will be reproduced in full
                                                                                                     quality testing. Two hundred and fourteen of these were selected for investigation, with a por-
for commonly used oral antibacterial drugs.        in EDM-30.
                                                                                                     tion of each sent to the drug regulatory authorities in the manufacturing country for analysis.
                                                   Available, free of                                    The report shows that the prevalence of substandard drugs is generally a much greater
Available from: The Medical Letter on                                                                problem than counterfeit drugs in both countries. Products which had passed laboratory tests
Drugs and Therapeutics, 1000 Main Street,          charge, from: Depart-
                                                                                                     were sometimes found to be counterfeit (deliberately mislabelled products, for example). The
New Rochelle, N.Y. 10801-7537, USA. Fax:           ment of Essential
                                                                                                     report concludes that laboratory tests alone are insufficient to determine whether a product is
+ 1 914 632 1733. Price 1–9 copies US$14           Drugs and Medicines                               counterfeit. Any investigation requires adequate resources, planning, and undercover work,
each, 10–99 copies US$11.20 each, 100+             Policy, World Health                              and must be undertaken in collaboration with drug regulatory authorities and manufacturers.
copies US$8.40 each. Special rates are avail-      Organization, 1211
able for subscribers to the journal, The           Geneva 27, Switzer-                               Available, free of charge, from: Department of Essential Drugs and Medicines Policy, World
Medical Letter on Drugs and Therapeutics.          land.                                             Health Organization, 1211 Geneva 27, Switzerland.


Issue No. 28 & 29, 2000
34                                                                                                                                      ESSENTIAL DRUGS MONITOR




  PUBLISHED                        LATELY


Narcotic and Psychotropic Drugs. Achieving Balance in National
Opioids Control Policy. Guidelines for Assessment, World Health
Organization, WHO/EDM/QSM/2000.4, 2000, 37 p.                                                                Updates on new formularies, treatment guidelines,
                                                                                                             essential drugs lists, drug bulletins and newsletters
    WHO estimates that by the year 2020 approximately 70% of the annual 20 million new
cancer cases will occur in developing countries, where most patients are diagnosed in the late                The Department of Essential Drugs and Medicines Policy produces a global index of
stages of the disease. It is at this time that pain is most prevalent. But cancer pain is frequently      formularies, therapeutic guides and essential drugs lists, which is available free of charge.
untreated and, even when it is, relief is often inadequate. While health worker training and              (Please note that we are unable to supply copies of the publications themselves. Requests
increased access to palliative care services can help, the publication focuses on solving the             should be addressed direct to the countries concerned). Some recent additions are:
problem of inadequate availability and use of pain medications, particularly opioid analgesics,           ◆ India, Himachal Pradesh: List of Essential Drugs. 1999. Department of Health and
in developing countries.                                                                                    Family Welfare, Government of Himachal Pradesh. Drugs by generic name, divided
    The authors state that opioid analgesics, such as codeine and morphine are “absolutely                  into 29 therapeutic groups.
necessary” for the management of cancer pain and that for moderate to severe pain there is no             ◆ Médecins Sans Frontières: Essential Drugs: Practical Guidelines. New editions of
substitute for opioids in the therapeutic group of morphine. But, because of their potential for            this useful manual for doctors, pharmacists, nurses and medical auxiliaries are avail-
abuse, opioids are classified as narcotic drugs.                                                            able. A first edition in Portuguese, and second editions in English and Spanish, will
    The International Narcotics Control Board, WHO and national governments report that                     soon be followed by a second edition in Arabic.
opioids are not sufficiently available for medical purposes. Reasons for this include the low
                                                                                                          ◆ Nepal: Standard Treatment Schedules for Health Posts and Sub-Health Posts,
priority of pain care in health systems, greatly exaggerated fears of addiction, overly restrictive
                                                                                                            3rd ed., 1999. Ministry of Health. Now available in English and Nepali. Includes
national drug control policies and problems in procurement, manufacture and distribution of
                                                                                                            principles of appropriate prescribing and dispensing, and advice for patients.
opioids. The publication presents guidelines for governments to determine whether their na-
tional drug control policies have the legal and administrative framework to ensure medical                ◆ Russia: Formulary 2000 (Russian Formulary System). 2000. Health of Men Founda-
availability of opioid analgesics, as recommended by the International Narcotics Control Board.             tion, Moscow. Guidelines for doctors on drug use. Approved and recommended by
                                                                                                            the Russian Federation Ministry of Health. In Russian.
Available, free of charge from: Department of Essential Drugs and Medicines Policy, World                 ◆ South Africa: Treatment Guidelines from South Africa’s Department of Health
Health Organization, 1211 Geneva 27, Switzerland.                                                           include:
                                                                                                            – National Guideline on Management and Control of Asthma in Children at Primary
                                                                                                               Level. 1999.
Beyond Our Means? The Cost of Treating HIV/AIDS in the Developing                                           – National Guideline on Primary Prevention and Prophylaxis of Rheumatic Fever
World, The Panos Institute, 2000, 59 p.                                                                        and Rheumatic Heart for Health Professionals at Primary Level. 1999.
                                                                                                            – Hypertension: National Programme for Control and Management at Primary Level.
     This report looks at the controversial and     health care systems – poor infrastructures,                1998.
complex issues surrounding access to HIV/           inadequate facilities, including lack of hospi-         – Diabetes: National Programme for Control and Management of Diabetes Type 2
AIDS treatments in developing countries. It         tal beds, laboratories and trained staff. The              at Primary Level. 1998.
states that at least 12 million people in the       second factor is a combination of the high cost       ◆ South-East Asia: Essential Drugs for Primary Health Care, 3rd edition. 2000. WHO
developing world are in urgent need of the          of antiretroviral and other drugs, and disputes         Regional Office for South-East Asia. The manual provides community health
antiretroviral drugs which can suppress HIV         over patenting and licensing rights for these           workers and auxiliary health personnel with guidelines on the use of 34 essential
and indefinitely postpone symptoms of AIDS.         products.                                               drugs. It also advises on treatment and referral requirements for 22 common medical
But the vast majority of these people live in           The publication provides an overview of             problems.
the world’s poorest countries, and while pro-       the issues surrounding access to treatment for
                                                                                                          ◆ Zimbabwe: EDLIZ. 4th Essential Drugs List and Standard Treatment Guidelines.
viding such treatment is theoretically possible,    AIDS, in order to encourage informed debate,
                                                                                                            2000. Ministry of Health and Child Welfare. Fewer drugs on the list (from 600 down
it is highly improbable in the foreseeable          further research and considered action. It is
                                                                                                            to 250) and updated advice for Zimbabwe’s health workers.
future, according to the authors.                   intended primarily for policy-makers, AIDS
     A number of factors lie behind this fail-      organizations and medical personnel.
ure to provide full treatment to those in need.                                                                                    Drug bulletins and newsletters
These vary from country to country, but, ac-        Available from: The Panos AIDS Programme,             ◆ Introducing Essential Drugs in Brief. Anyone involved in national drug policy im-
cording to the publication, include lack of         9 White Lion Street, London N1 9PD, UK.                 plementation who wants a quick update on the latest WHO activities carried out with
political will, unhelpful economic policies         Tel: + 44 20 7278 1111, fax: 44 20 7278 0345.           and for countries should subscribe to the bulletin, Essential Drugs in Brief. The bul-
(such as taxing medical products), lack of rel-     Available on the Panos Web site: www.                   letin, which will be published twice a year, shares information on the latest country
evant information and lack of appropriate           panos.org.uk Price: £5/US$10. Copies are                support provided or coordinated by EDM’s extended Drug Action Programme team
distribution mechanisms. The authors believe        available, free of charge, to resource-poor             through country, regional and Headquarters’ offices.
two other factors are critical. The first is weak   NGOs in developing countries.                         ◆ And a new look for the WHO Pharmaceuticals Newsletter, which has been rede-
                                                                                                            signed and has had some content changes. Articles will be restricted to subjects more
                                                                                                            directly related to drug quality assurance and safety. Some more general information,
Integrating Public Health Concerns into Patent Legislation in Developing                                    such as new developments, guidelines, and regulations of a general nature, will be
Countries, C. Correa, South Centre, 2000, 124 p.                                                            published only in the quarterly journal WHO Drug Information. The WHO Collabo-
                                                                                                            rating Centre is now providing the Safety of Medicines section for International Drug
    This publication presents options for           covered include patentability requirements,             Monitoring. The Centre’s Adverse Reactions Newsletter is being discontinued.
the design and implementation of public-            special cases in pharmaceuticals, disclosure,         ◆ With WHO support the Delhi Society for the Promotion of Rational Use of Drugs
health sensitive patent policies in developing      exceptions to exclusive rights and compulsory           (DSPRUD) launched its Medical Newsletter in July 1999, to help health care profes-
countries. It is particularly concerned with        licensing.                                              sionals update existing knowledge about drug therapy. Distributed free of charge to
the TRIPS Agreement (Trade-Related Aspects              The publication is primarily intended for           doctors, the Newsletter contains a digest of various published articles, which include
of Intellectual Property Rights) which covers       policy-makers, particularly ministries of               drug reactions, news and review articles.
protection of pharmaceutical products and           health and government lawyers responsible
                                                                                                          ◆ WHO/EDM is also supporting Spectrum, India-WHO Es-
processes. World Trade Organization mem-            for drafting TRIPS compliant national
                                                                                                            sential Drugs Programme Newsletter, which covers the
ber countries are obliged to comply with the        legislation. For further details see page 36.
                                                                                                            activities of the Delhi Society for the Promotion of Rational
minimum standards of the Agreement. But,
                                                                                                            Drug Use and the Essential Drugs Programme.
the author points out, they also have con-          Available, free of charge, from: South Cen-
siderable room to develop their own patent          tre, Case Postale 228, 1211 Geneva 19,                ◆ Practical Pharmacy packs. Complete sets of Practical Phar-
and other intellectual property laws in re-         Switzerland. Also available on the South                macy are now available to developing countries, free of
sponse to the characteristics of their legal        Centre Web site at: www.southcentre.org/                charge, while stocks last. This newsletter for health work-
systems and development needs. Topics               publications/publichealth/toc.htm                       ers of all levels includes easy-to-read information on basic
                                                                                                            aspects and skills of pharmacy work. Contact: Echo Inter-
                                                                                                            national Health Services Ltd, Ullswater Crescent, Coulsdon,
                                                                                                            Surrey CR5 2HR, UK. Tel: + 44 20 8660 2220, fax: + 44 20
Guidelines for the Regulatory Assessment of Medicinal Products for Use                                      8668 0751.
in Self-Medication, World Health Organization, WHO/EDM/QSM/00.1,
2000, 32 p.
    Reclassification of medicinal products from sale on prescription only to non prescription          Globalization, Patents and Drugs: An Annotated Bibliography, 2nd ed.,
(over-the-counter) sale is increasingly common. Drug regulatory and health authorities have to         World Health Organization, Health Economics and Drugs, EDM Series
consider the types of medicinal products for which reclassification is appropriate, safe and           No.10, EDM/PAR/01.1, 2001, 52 p.
rational in the interest of public health.
    The Guidelines suggest criteria and methods which drug regulatory agencies can use to                  The impact of globalisation and trade           articles and country specific studies. The
determine the suitability of medicinal products for use in self-medication. They are also in-          agreements on access to drugs is an increas-        document concludes with a section on useful
tended for marketing authorisation holders applying for the classification of a prescription           ingly important issue. This annotated               Web sites.
product to be changed to non prescription sale. Guidance is given on documentation for new             bibliography is intended for those in the health
active substances, never marketed as prescription medicines, to accompany applications for             sector with no particular legal background,
self-medication marketing authorisation.                                                               who want an overview of the issues and argu-        Available, free of charge, from: Department
                                                                                                       ments involved. It directs readers to key           of Essential Drugs and Medicines Policy,
Available from: World Health Organization, Marketing and Dissemination, 1211 Geneva 27,                reports, books and articles from technical and      World Health Organization, 1211 Geneva 27,
Switzerland. Price: Sw.fr.10, US$9, and in developing countries Sw.fr.7.                               scientific journals, subdivided into general        Switzerland.


                                                                                                                                                                     Issue No. 28 & 29, 2000
ESSENTIAL DRUGS MONITOR                                                                                                                                                                                                35




                          TRADITIONAL                      MEDICINE



                        Research focuses on                                                                        India: protecting
                        traditional antimalarials
                                 ith modern pharmaceuticals          Tanzania, to move the process forward.
                                                                                                                   its heritage of
                        W        often unavailable and unafford-
                                 able in the areas most affected
                                 by malaria, and drug resistance
                                                                        Delegates included biological and
                                                                     social scientists, doctors, traditional
                                                                     healers and policy-makers from Africa,
                                                                                                                   medicinal plants
                        increasing, the use of herbal anti-          Asia, Europe and the Americas. They
                                                                                                                           he Indian Government is setting          by a non profit NGO assisted by an ad-

                                                                                                                     T
                        malarials is very common. But there          developed four specialist groups to
                                                                                                                           up a programme to protect and            visory panel of international experts,
                        has been almost no research into their       implement a research strategy which
                                                                                                                           promote its rich tradition in her-       and it is hoped that other international
                        clinical effectiveness.                      will contribute to malaria control pro-               bal medicines. One of the main           organizations will become involved.
                            Developing a strategy for more           grammes. The topics covered by the            aims is to prepare standardised formula-
                        evidence-based use of traditional            groups are: policy, advocacy and              tions of traditional medicines that will         Drawing on local
                        medicines against malaria, has led           funding; pre-clinical studies; clinical       undergo the same regulatory procedures,          knowledge
                        WHO’s Special Programme for Re-              development; and repellance and               including clinical trials, as modern
                        search and Training in Tropical Medi-        vector control.                               pharmaceuticals.                                     One of the programme’s key elements
                        cine to team up with the UK’s Global            Future plans include updating the              A new Department for Indian Systems          is the involvement of local people, who
                        Initiative for Traditional Systems of        Research Initiative’s database of tradi-      of Medicines and Homeopathy has been             will be employed to identify, document
                        Health. They have formed a Research          tional treatments for malaria, and            set up and a Biodiversity Bill is go-
                                                                                                                   ing through Parliament. This will
                        Initiative on Traditional Antimalarials,     regulatory guidelines for traditional
                                                                                                                   establish a National Biodiversity
                        and in November 1999 the two groups          medicines and natural products, case          Board to oversee access to and use of
                        co-sponsored a meeting in Moshi,             studies of their use, clinical efficacy,      medicinal plants, as well as applying
                                                                                           safety, screen-         for patents when appropriate.
                                                                                           ing and clinical




                                                                                                                                                                                                                                Photo: WHO/A. Kochar
                                                                                           evaluation. ❏           Clinical trials
                                                                                                                       A pilot project will begin in the
                                                                                                                   Western Ghats region, where experts
                                                                                            Source: TDR News,      will study and document medicinal
                                                                                            June 2000.             plants. A small formulations unit will Crushing and storing medicinal plants at a
                                                                                                                   process plants into medicines, which processing plant in Kanzicode, India
                                                                                                                   will then undergo clinical trials to in-
                                                                                                                   ternational standards. This work will form   and cultivate the plants, and participate
                                                                                                                   part of a digital database of India’s tradi- in running the formulations unit and
                                                                                                                   tional knowledge, which will be included     therapeutic centre. There are plans to in-
                                                                                                                   in the World Intellectual Property Organi-   volve local schools, and to set up a home
Photo: WHO/H. Anenden




                                                                                                                   zation’s patent classification system, and   for the elderly who will be encouraged to
                                                                                            Research into          made available to patent offices world
                                                                                            herbal antimalarials
                                                                                                                                                                pass on their knowledge of local plants
                                                                                            aims to improve the
                                                                                                                   wide. The Government hopes the move          and their uses. ❏
                                                                                            plight of sufferers,   will help to prevent patents being granted
                                                                                            such as this patient   on traditional Indian plants and remedies.
                                                                                            in Congo                   The pilot programme will be run          Source: Scrip No.2547, 9 June 2000.



                          WORLD             TRADE



                        Delhi Declaration                                                                          Fears over new regional patent
                                                                                                                   agreement
                        on trade issues                                                                                     new agreement on patent protec-         only possible between OAPI Member States


                                balancing of rights and obligations under the TRIPS Agreement was one of
                                                                                                                    A       tion for medicines could endanger
                                                                                                                            people’s health in some of Africa’s
                                                                                                                            poorest nations, according to
                                                                                                                                                                    whereas lower prices might be found in
                                                                                                                                                                    other parts of the world.
                                                                                                                                                                        OAPI counters that in revising the Ban-


                         A
                                                                                                                   Médecins Sans Frontières. The organization       gui Accord Member States have affirmed
                                the main demands of the Delhi Declaration released at the end of a two-
                                                                                                                   has urged countries not to ratify the Bangui     their conviction that bringing intellectual
                                day workshop on trade issues held in New Delhi in October 1999. In a               Accord, created last year by 15 French-          property rights into line with the TRIPS
                                hard-hitting statement the 65 delegates called for strong, clearly defined         speaking African nations. In these countries,    Agreement will attract investors and stimu-
                        compulsory licensing provisions; protection of traditional knowledge from all forms        patents are granted through the African In-      late technology transfer. In an Information
                        of patenting; and strengthening of existing anti-monopoly practices by developing          tellectual Property Organization (OAPI),         Memo* the Organization says that its crit-
                        countries.                                                                                 which acts as a patent office for all its Mem-   ics need to look elsewhere for the reasons
                            Participants argued that as international trade agreements contribute to widen-        ber States. Patents are granted and regulated    why many Africans lack access to essential
                                                                                                                   according to the Bangui Agreement (signed        drugs.
                        ing the socioeconomic and technological gap between developed and developing
                                                                                                                   in 1977), which was recently revised to              Under WTO rules, the so-called “least-
                        countries, it is necessary to have an alternative framework, incorporating greater         comply with WTO rules, increasing patent         developed countries” – 10 of which are
                        self-reliance.                                                                             protection from 10 to 20 years.                  covered by the Bangui Accord – have until
                            As well as the TRIPS (Trade-related Aspects of Intellectual Property Rights)               A report 1 issued jointly by WHO,            January 2006 to change their patent sys-
                        Agreement the national and international experts present also addressed issues             UNAIDS and MSF says the new treaty,              tems. But if the Accord is ratified by at least
                        such as food security, competition policies and electronic commerce.                       which has not yet come into force, could         10 members, countries will find themselves
                            The International Brainstorming Workshop on World Trade Organization                   lead to increased prices for medicines. This     forced to change their systems immediately.
                                                                                                                   is because the new Bangui Agreement is           So far eight nations have ratified. ❏
                        Agreements and People’s Concerns was organized by the Centre for Study of
                                                                                                                   more stringent than the TRIPS Agreement
                        Global Trade System and Development and the National Working Group on                      and provides little come back in case of         Reference
                        Patent Laws. ❏                                                                             patent abuse, the report states. Compulsory
                                                                                                                                                                    1.   MSF/WHO. Revue of the pharmaceutical policy in
                                                                                                                                                                         Cameroon – Medicine patents in francophone Africa.
                                                                                                                   licences are only available provided that             Joint Mission MSF-WHO-UNAIDS. Geneva: Médecins
                                                                                                                                                                         Sans Frontières and World Health Organization; 2000.
                        Copies of the Delhi Declaration are available from: Centre for Study of Global Trade       the patented drug can be manufactured                 (Available in English and French).
                        System and Development, A-388, Sarita Vihar, New Delhi 110 044, India. Tel/fax: + 91 11    locally, yet there is little manufacturing       * The Information Memo is available on the web at:
                        694 7403, e-mail: wgkeayla@del6.vsnl.net.in                                                capacity in the region. Parallel imports are     http://www.oapi.wipo.net/



                        Issue No. 28 & 29, 2000
36                                                                                                                            ESSENTIAL DRUGS MONITOR




  WORLD              TRADE




Patents from a public
health perspective
         ➢ CARLOS CORREA*                      including eligibility requirements, scope      of an integrated medium- or long-term             more than 880 million people lack access
                                               of protection, exceptions to exclusive         patent policy. In some cases, a country           to health care. Of the more than 33 mil-
         he Agreement on Trade-Related         rights and compulsory licences – in quite      may – within limits permitted by its              lion HIV-positive people in the world,

  T      Aspects of Intellectual Property
         Rights (TRIPS) requires all WTO
         Member Countries to adapt their
                                               different ways. In drawing up their own
                                               intellectual property rights rules, policy-
                                               and law-makers in developing countries
                                                                                              international obligations – opt for differ-
                                                                                              ent levels of protection in different areas
                                                                                              of intellectual property. The level would
                                                                                                                                                95% live in developing countries, and
                                                                                                                                                most of them cannot afford required
                                                                                                                                                drugs. To deal with this dramatic situa-
laws to the minimum standards set forth        need to be aware of this. They will be         depend on its competitive position and the        tion, an integrated approach to the deeply
by the Agreement, within established           most successful in meeting their own           expected role of national and foreign in-         inter-related issues of national health
transitional periods. Developing countries     needs if they can draw on the experiences      vestors and technology suppliers. It may,         policy, pharmaceutical policy and patent
face a special challenge in conforming         of national systems worldwide.                 for instance, be possible to emphasise            policy is required. None of these poli-
to international trade obligations, par-           Some countries – particularly devel-       protection for information technologies,          cies can be framed or implemented in
ticularly the TRIPS Agreement which            oped countries – have opted for legal          through high levels of copyright pro-             isolation.
covers intellectual property rights of         systems that confer strong patent rights.      tection for computer programmes and                   If developing countries are not to be
pharmaceutical products and processes.         They have done so in order to protect rev-     databases. At the same time lower levels          disadvantaged by new trade rules, they
    The way in which countries reform          enues from their already established
their legislation may have a significant       technological base and to promote in-
impact on public health policies, and par-     vestment in technological innovation.
ticularly on access to drugs. Any property     Considerable debate exists in such coun-
rights system must strike a balance be-        tries, however, on the level and scope of
tween creating incentives for innovation,      protection which are optimal to foster in-
and people’s need for availability and         novation without unduly restricting the
affordability of protected goods. So when      free circulation of ideas and stifling com-
they draw up their own intellectual            petition. A growing concern is voiced in
property rights rules, it is important that    some countries on the shortcomings of
developing countries realise the scope         the examination process and the prolif-
they have – within the framework of in-        eration of low quality patents. Moreover,
ternational treaties – to produce their own    the economics of patent law is still an un-
patent laws.                                   certain area, for which a robust theoretical




                                                                                                                                                                                                 Photo: WHO/PAHO/C. Gaggero
    The TRIPS Agreement does not es-           framework and empirical evidence are
tablish a uniform international law or         lacking.
even uniform legal requirements. World
Trade Organization Member Countries
must comply with the Agreement’s mini-         Checks and balances
mum standards. But countries may                   Countries with less advanced tech-
legitimately adopt regulations that ensure     nologies may prefer to promote the
a balance between the minimum stand-           transfer of those technologies needed for      Taking the medicine in Guatemala. International trade agreements don’t just affect people in the
ards of intellectual property protection       development, and to preserve and en-           rich industrialised nations
and the public good. Moreover, they can        hance competition. They do so in order
adopt measures which are conducive to          to secure access to goods, services and        of protection may be given in areas where         must look at options for designing and
social and economic welfare (Article 7         technologies on the most favourable            local industrial and technological ca-            implementing public-health-sensitive
of the Agreement). These include steps         market conditions. Even in countries with      pabilities are low, and unlikely to be            patent policies. There must be a balance
necessary to protect public health, nutri-     the strongest intellectual property rights     significantly improved through a high             between the public and private interests
tion and the public interest in sectors of     protection, national laws provide for          standard of patent protection.                    involved, including the rights of states,
vital importance for socio-economic and        checks and balances, to protect against            The way in which such options are             patients and suppliers of health-related
technological development. Countries           possible abuse of the powers conferred         implemented should be consistent with             goods and services. ❏
can also adopt measures to prevent the         by protection.                                 the country’s level of development, par-
abuse of intellectual property rights              Policy-makers should consider cross-       ticularly its research and manufacturing
(Article 8.1 and 8.2).                                                                                                                          * Carlos Correa is Director of the Masters
                                               cutting issues when they design a national     capabilities in the pharmaceutical sector.
    In those countries that are bound to                                                                                                        Programme on Science and Technology
                                               patent system, for example: protection of      The options followed by a large develop-          Policy and Management at the University of
introduce patent protection for pharma-        public health and the environment; pro-        ing country with significant capabilities         Buenos Aires, Argentina. He is a specialist
ceuticals as a result of TRIPS, patents will   motion of competition and technology           may differ from those preferred by a small        in global intellectual property law, and was
only be available for products for which       transfer; protection of consumers; and         economy which is totally or substantially         involved in the negotiations on TRIPS during
a patent application was filed after 1 Janu-   support for small local inventors. Coun-       dependent on foreign supplies of pharma-          the Uruguay Round of trade negotiations. Fur-
ary 1995. This means that other products       tries should also respect inventors’ rights                                                      ther information on legal options for drawing
                                                                                              ceuticals. Likewise, patent laws may
(including those already applied for or                                                                                                         up TRIPS-compatible national legislation can
                                               to a reward for contributions to technical     evolve as a country develops. It should
patented in other countries, or marketed                                                                                                        be found in Professor Correa’s new books,
                                               progress. Other regulatory measures            be remembered, however, that problems
before that date) will remain in the pub-                                                                                                       Integrating public health concerns into pat-
                                               affecting public health, such as those         of access to drugs caused by poverty
lic domain. The exception is where the                                                                                                          ent legislation in developing countries, and
                                               relating to medicines’ registration, must      and low income are common to most
national law permits retroactive protec-                                                                                                        Intellectual property rights, the WTO and de-
                                               be carefully considered, so that there is a    developing countries.                             veloping countries. (See Published Lately
tion of the so-called “pipeline” products,
                                               consistent legal framework that improves                                                         pages 33 and 34).
as is the case in Brazil.
                                               access to medicines.
                                                                                              Considering                                       Other useful documents include Globaliza-
Scope for national                                                                            options                                           tion and access to drugs. Perspectives on the
differences                                    Health-sensitive                                                                                 WTO/TRIPS Agreement. Health Economics
                                               approach                                           The protection of public health is one
    Given diverse national objectives, it                                                                                                       and Drugs, EDM Series No. 7, and Globali-
                                                                                              of the most pressing issues in developing
                                                                                                                                                zation, patents and drugs: an annotated
is not surprising that different countries’       A health-sensitive approach to patent       countries. A large part of the global popu-       bibliography, Second edition. Health Eco-
patent systems diverge, in some cases          legislation might address short-term           lation still lacks access to essential drugs.     nomics and Drugs, EDM Series No. 10. Both
significantly. There is no single “patent      emergencies that justify different tempo-      In the poorest parts of Africa, for instance,     documents are available, free of charge,
system”. Moreover the solutions adopted        rary measures (for instance, medicines’        over 50% of the population lack that ac-          from: Department of Essential Drugs and
in particular countries have changed over      supply in cases of epidemics or natural        cess. An estimated 1,5 billion people are         Medicines Policy, World Health Organiza-
time. They treat specific patent issues –      disasters). Or the approach may be part        not expected to survive to age 60, and            tion, 1211 Geneva 27, Switzerland.


                                                                                                                                                          Issue No. 28 & 29, 2000

				
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