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					                       Utrecht   I WHO Winter Meeting 2010


      Utrecht
 WHO Winter




                                                       Programme Meeting report
Meeting 2010
                        7 - 8 January 2010



     Utrecht - WHO Collaborating Centre
                                                                  1


         for Pharmacoepidemiology and

          Pharmaceutical Policy Analysis

                Utrecht, The Netherlands




    Location: Faculty Club Helios, Utrecht
2




    Foto cover: Michael Kooren
                               Utrecht   I WHO Winter Meeting 2010




                                                              Programme Meeting report
Utrecht – WHO Winter Meeting 2010

                           7 - 8 January 2010



                                                                           3



                                    Programme




       Utrecht - WHO Collaborating Centre for
                  Pharmacoepidemiology and
               Pharmaceutical Policy Analysis
                    Utrecht, The Netherlands
    Index


    Topic                  Page




    Welcome                   5

    General information       6

    Time schedule             7

    Paper discussions         8

    List of participants     10

    Overview abstracts       13




4
                                                                               Utrecht   I WHO Winter Meeting 2010

Welcome


We are very pleased to welcome all of you in Utrecht for the 2010 edition of the Utrecht - WHO Collaborating Centre for
Pharmacoepidemiology and Pharmaceutical Policy Analysis Winter Meeting.

We proudly present this years’ programme with a mixture of established and young researchers, who are excited to share
and discuss their experiences in the field of pharmaceutical policy analysis.

The first day focuses on “IMS data as a resource for pharmaceutical policy analysis”. Traditionally, IMS data was primarily
used for market analysis research and has been neglected by academia with few notable exceptions. Now IMS data is
frequently used in the academic and public domain, which can be attributed to IMS’s willingness to share their data. Five
case examples will illustrate policy research based on IMS Health data, and lessons learned from these case examples will
be discussed by experts in their field.

Researchers from different backgrounds – both in terms of professional as well as geographical background – will be given
the floor on Friday to discuss their ongoing work. We sincerely hope that these discussions will contribute to bringing
evidence-based policy making on pharmaceuticals to a higher level.

With an attendance that almost doubles last years’ attendance, the meeting brings together researchers who are committed
to make a difference in measuring and evaluating policy initiatives. We hope that this meeting will result in exciting
discussions and inspiring new thoughts.
May you all enjoy!
                                                                                                                              5
On behalf of the Organizing Committee,



                                                                                   Bert Leufkens and Aukje Mantel
    General Information
    Location
    Faculty Club
    Achter de Dom 7
    3512 JN Utrecht
    Phone: +31 (0)30 253 99 11

    Date
    Thursday, 7 January – Friday, 8 January, 2010

    For all practical matters during the meeting, please contact:
    Aukje Mantel (a.k.mantel@uu.nl)
    Mobile: +31 (0)615859343



    Organizing Committee

    Utrecht - WHO Collaborating Centre for Pharmacoepidemiology and Pharmaceutical Policy Analysis
    -        Bert Leufkens
    -        Aukje Mantel
    -        Joëlle Hoebert

    Department of Essential Medicines and Pharmaceutical Policies, World Health Organization

6
    -        Richard Laing

    Acknowledgement
    We gratefully acknowledge Peter Stephens (IMS Health) for his suggestions and contributions to the program.
                                                                               Utrecht   I WHO Winter Meeting 2010

Time schedule
Thursday 7 January IMS as a resource for pharmaceutical policy analysis

09:00 – 10:00       Registration, coffee and tea
10:00 – 10:15       Welcome – Objectives of the Meeting                   Bert Leufkens (UU) and Richard Laing (WHO)
10:15 – 11:00       Introduction: Use of IMS Health data for
                    Pharmaceutical Policy Analysis                        Andreas Gieshoff (IMS)
11:00 – 11:15       Coffee break
11:00 – 11:30       Introduction of five case examples                    Bert Leufkens (UU)
11:30 – 12:00       Low persistence, and discovering reasons
                    for discontinuation                                   Judith Jones (The Degge Group, USA)
12:00 – 12:30       Strengths and limitations of using market
                    intelligence data to analyze antibiotic consumption
                    in eight Latin American countries 1997 - 2007         Veronika Wirtz (National Institute of Public
                                                                          Health, Mexico)
12:30 – 14:00       Lunch

14:00 – 14:30       Monitoring paediatric medications prescribing using
                    IMS data                                              Ian Wong (Centre for Peadiatric Pharmacy
                                                                          Research, UK)
14:30   –   15:00   Drug safety: SSRIs and suicide                        Peter Stephens (IMS)
15:00   –   15:30   Impact of the global recession                        Richard Laing (WHO)
15:30   –   16:00   Coffee break
16:00   –   17:25   Expert panel discussion – lessons learned             Per Troein (IMS), Dennis Ross-Degnan (Harvard
                                                                                                                            7
                                                                          Medical School, USA), Frank de Vries (UU), Vera
                                                                          Luiza (NAF, Brazil)
17:25 – 17:30       Day closure                                           Richard Laing (WHO) and Bert Leufkens (UU)

17:30 – 18:30       Drinks



Friday 8 January

From 08:30          Coffee
09:00 – 10:30       Paper discussion – 2 parallel sessions
                    1a: Pharmacovigilance
                    1b: Regulatory issues and challenges (I)
10:30 – 11:00       Coffee break
11:00 – 12:30       Paper discussion – 2 parallel sessions
                    2a: Regulatory issues and challenges (II)
                    2b: Country studies (I)

12:30 – 14:00       Lunch

14:00 – 15:45       Paper discussion – 2 parallel sessions
                    3a: Pricing valuation
                    3b: Country Studies (II)
15:45 – 16:00       Coffee break

16:00 – 16:30       Wrap up and concluding remarks
    Paper discussions


    Session 1a - Friday 8 January
    09:00 – 10:30 - parallel session -
    Pharmacovigilance
    Session Chairs:   Marieke de Bruin (UU)

    Nr   Author        Title
    1    Giezen        Evaluation of the recently proposed classification system of adverse events for biologicals
    2    Vaz           Strategies to increase spontaneous Adverse Drug Reaction reporting rates
                       among Portuguese pharmacists
    3    Willemen      Lifestyle drugs and the reporting of psychiatric adverse events in randomised clinical trials
    4    Ebbers        The Impact of Periodic Safety Update Reporting on Safety-Related Regulatory Actions




    Session 1b - Friday 8 January
    09:00 – 10:30 - parallel session -
8   Regulatory issues and challenges (I)
    Session Chairs: Aukje Mantel (UU)

    Nr   Author        Title
    5    Tafuri        Therapeutic indications in oncology: emerging features and regulatory dynamics
    6    Piriou        Medicines promotion: Assessing the scope and impact of regulation
    7    Bruno         What is growing in the area of Advanced therapy medicinal products? Bridging the ATMP clinical
                       pipeline to the EU regulatory framework
    8    Putzeist      Scientific Advice in the marketing authorization procedure: A Cross-sectional Content Analysis




    Session 2a - Friday 8 January
    11:00 – 12:30 - parallel session -
    Regulatory issues and challenges (II)
    Session Chairs: Aukje Mantel (UU)

    Nr   Author        Title
    9    Alves         Assessing patient and consumer input into the review of medicines’ information at the EMEA
    10   Hernandez     Drug Life Cycles as a Tool in Drug Regulation: The Case of Selective Serotonin Reuptake
                       Inhibitors (SSRIs) and safety
    11   Perehudoff    Under the Influence: Association between corporate sponsorship and policy perspectives of Pan-
                       European patient and consumer groups.
    12   Crombag       Accelerating Dosage Revisions of Newly Approved Drugs
                                                                            Utrecht   I WHO Winter Meeting 2010

Session 2b - Friday 8 January
11:00 – 12:30 - parallel session -
Country studies (I)
Session Chairs: Richard Laing (WHO) and Ye Lu (Fudan University)

Nr     Author        Title
13     Sato          Household medicines use in Ghana: a quantitative and qualitative exploration into a dual system
14     Ssewaya       Utilisation of patient assessment and pill-count data in understanding adherence to antiretroviral
                     therapy in Uganda’s settings
15     Ankrah        A descriptive report on the first hundred HIV/AIDS cases on antiretroviral therapy at the Korle-Bu
                     teaching hospital, Accra, Ghana
16     Gyansa-Lutterodt Assessing the Ghanaian Public Health Sector Medicines Procurement and Supply
                     Management Systems




Session 3a – Friday 8 January
14:00 – 15:45 - parallel session -
Pricing valuation
Session Chairs: Bert Leufkens (UU) and Kees de Joncheere (WHO)

                                                                                                                          9
Nr     Author        Title
17     Adamski       Review of risk sharing schemes for pharmaceuticals: considerations, critical evaluation and
                     recommendations for European payers
18     Milevska-Kostova Reforming the medicine prescribing practices in SEE: case of policy and implementation
                     changes in Macedonia
19     Dagron        Is evaluation of the cost-benefit of drugs feasible? – Current developments in Switzerland
20     Leopold       How much of the price variance of medicines can be explained by national pharmaceutical
                     polices?
21     Kaplan        Is the UNITAID Patent Pool Initiative Making a Difference?




Session 3b - Friday 8 January
14:00 – 15:45 - parallel session -
Country Studies (II)
Session Chairs: Liset van Dijk (NIVEL) and Anita Wagner (Harvard Medical School)

22     Hoebert       A study on the uptake of TNF inhibitors in different European Member States
23     Ziganshina    Medicine consumption and expenditure databases’ analysis as the basis for policy changes
24     Buysse        Impact of economic recession on the consumption of medicines
                     An analysis on “ATC-2, 3 and 4” level
25     Vd Ham        The selection of essential medicines
26     Cameron       Differences in the availability and price of medicines used for chronic conditions compared
                     to those used for acute conditions
     List of participants            (– as of 15 December 2009 –)


      Jakob Adamski
             Ministry of Health, Poland
      Kemi O Ailoje
             University of Lagos, Nigeria
      Teresa Alves
             Utrecht University, The Netherlands and Health Action International Europe, The Netherlands
      Karolina Andersson
             Nordic School of Public Health, Sweden
      Daniel Ankrah
             Korle-Bu Teaching Hospital, Ghana
      Martin Auton
             Health Action International Global, The Netherlands
      Henk ten Besten
             I+ solutions, The Netherlands
      Evelien van Bijnen
             Netherlands Institute for Health Services Research (NIVEL), The Netherlands
      Marieke de Bruin
             Utrecht University, The Netherlands
      Raffaele Bruno
             Utrecht University, The Netherlands
      Iris Buysse
             Utrecht University, The Netherlands
      Ali Cameron
10
             World Health Organization, Switzerland
      Renia Coghlan
             Global Health at Medicines for Malaria Venture, Switzerland
      Rose Crombag
             Utrecht University, The Netherlands
      Stephanie Dagron
             Institute for Biomedical Ethics, Switzerland
      Dennis Ross-Degnan
             Harvard Medical School, USA
      Liset van Dijk
             Netherlands Institute for Health Services Research (NIVEL), The Netherlands
      Saskia van Dongen
             Utrecht University, The Netherlands
      Hans Ebbers
             Utrecht University, The Netherlands
      Marg Ewen
             Health Action International Global, The Netherlands
      Andreas Gieshoff
             IMS Health, Germany
      Thijs Giezen
             Utrecht University, The Netherlands
      Christine Gispen
             Medicines Evaluation Board, The Netherlands
      Martha Gyansa-Lutterodt
             Ministry of Health, Ghana
      Rianne van den Ham
             Utrecht University, The Netherlands
      Francisco Hernandez
             Utrecht University, The Netherlands
                                                                          Utrecht   I WHO Winter Meeting 2010

 Joëlle Hoebert
       Utrecht University, The Netherlands
 Judith Jones
       The Degge Group, USA
 Warren Kaplan
       Boston University School of Public Health, USA
 Mark Koopmanschap
       Instituut Beleid & Management Gezondheidszorg, The Netherlands
 Richard Laing
       World Health Organization, Switzerland
 Christine Leopold
       Gesundheit Österreich GmbH, Austria
 Bert Leufkens
       Utrecht University, The Netherlands
 Carlos Liang
       Utrecht University, The Netherlands
 Ye Lu
       Fudan University, China
 Vera Luiza
       National School of Public Health (ENSP), Brazil
 Aukje Mantel
       Utrecht University, The Netherlands
 Femke Markus
       Access to medicine index, The Netherlands
 Neda Milevska-Kostova
                                                                                                                11
       University of Sheffield, United Kingdom
 Ellen Moors
       Utrecht University, The Netherlands
 Jocelyn Musters
       Access to medicine index, The Netherlands
 Anne Paschke
       VU Amsterdam, The Netherlands
 Dindoust Payam
       Iran University of Medical Science, Iran
 Katrina Perehudoff
       Health Action International Europe, The Netherlands
 Toine Pieters
       Utrecht University, The Netherlands and VU University Amsterdam, The Netherlands
 Carole Piriou
       Health Action International Europe, The Netherlands
 Michelle Putzeist
       Utrecht University, The Netherlands
 Ilse Roubos
       Utrecht University, The Netherlands
 Azusa Sato
       London School of Economics, United Kingdom
 Margreet Scheurs
       Ministry of Health, Welfare and Sport, The Netherlands
 Achilles Ssewaya
       Amsterdam School for Social Research (ASSR), The Netherlands
 Peter Stephens
       IMS Health, United Kingdom
 Pieter Stolk
       TIPharma, The Netherlands
      Giovanni Tafuri
             Utrecht University, The Netherlands and Italian Medicines Agency (AIFA), Italy
      Fola Tayo
             University of Lagos, Nigeria
      Per Troein
             IMS Health, United Kingdom
      Francesco Trotta
             Italian Medicines Agency (AIFA), Italy
      Maria Laura Varela
             Zaragoza Logistics Center, Spain
      Inez Vaz
             Medicinal University of Porto, Portugal
      Sabine Vogler
             Gesundheit Österreich GmbH, Austria
      Frank de Vries
             Utrecht University, The Netherlands
      Anita Wagner
             Harvard Medical School, USA
      Grace Wangge
             Utrecht University, The Netherlands
      Jan Warmerdam
             IMS Health, The Netherlands
      Bart Wijnberg
             Ministry of Health, Welfare and Sport, The Netherlands
      Marjolein Willemen
12
             Utrecht University, The Netherlands
      Veronika Wirtz
             National Institute of Public Health, Mexico
      Ian Wong
             Centre for Paediatric Pharmacy Research, United Kingdom
      Serge Xueref
             Global Fund, Switzerland
      Lilia Ziganshina
             Kazan State Medical Academy, Russia
                                                                                      Utrecht   I WHO Winter Meeting 2010

    Overview abstracts

                                          Evaluation of the recently proposed classification system
1                                                                 of adverse events for biologicals

     T.J. Giezen       , A.K. Mantel-Teeuwisse
                   (1,2)
                                                         , S.M.J.M. Straus
                                                     (1,2)                    (2)
                                                                                    H.G.M. Leufkens   (1,2)
                                                                                                              A.C.G. Egberts   (1,3)

                                                                                   1. Utrecht University, The Netherlands
                                                             2. Medicines Evaluation Board, The Hague, The Netherlands
                                                                   3. University Medical Center Utrecht, The Netherlands




    Background
    The validity of the traditional classification of adverse events (AEs) in type A and B is debated for biologicals. According
    to this system immunological reactions are classified as type B AEs since these are not related to the pharmacological
    activity of the drug and are non-predictable. However, for biologicals these can be expected due to the protein nature and
    should therefore be classified as a type A AE. A classification system of AEs of biological was recently proposed, AEs were
    classified in five classes: type _ (high cytokine and cytokine release syndrome); type _ (hypersensitivity); type _ (immune
    (cytokine) imbalance syndrome); type _ (cross-reactivity); type _ (non-immunological side effects)1. This new classification
    system is important since it will help to predict AEs based on the characteristics of the biologicals. Pharmacovigilance can
    therefore be targeted towards these expected AEs. However, this system has not been validated in clinical practice.

    Objective
    To validate the new classification system of AEs for biologicals.
                                                                                                                                       13
    Methods
    Data will be obtained from the International Drug Monitoring Program of the WHO. The 100 most frequently reported AEs
    reported for biological, approved between January 1995 and December 2008 in the US and/ or the EU will be selected.
    ADRs will be selected at the MedDRA preferred term level.
    For each biological a Reporting Odds Ratio (ROR) will be calculated for each AE as a measure of disproportionality. Based
    on the ROR, AEs will be clustered using HCA and multidimensional scaling, which will be used to validate the system.
14
                                                                                  Utrecht   I WHO Winter Meeting 2010

                                       Strategies to increase spontaneous Adverse Drug Reaction
2                                                  reporting rates among Portuguese pharmacists

                                                             I. Vaz     , M. T. Herdeiro(2), A. Figueiras
                                                                      (1)
                                                                                                               , J. Polónia(1)
                                                                                                             (3)

                                                                 1. Faculdade de Medicina da Universidade do Porto, Portugal
                                            2. Centro de Investigação em Tecnologias da Saúde (CITS), IPSN-CESPU, Portugal
                                                                           3. Universidade de Santiago de Compostela, Spain




    Background
    Adverse Drug Reactions (ADR) are an important cause of morbidity and mortality in developed countries. In Portugal, as in
    many other countries, ADR reporting rates are relatively low[1-3]. As a consequence, the data transmitted to the Medicines
    Regulatory Authority, does not effectively represent the real magnitude of adverse events.

    Objective
    Our aim was to increase the number and relevance of ADR reporting among pharmacists, through the implementation of
    workshops and telephone interviews.

    Method
    A cluster-randomized controlled trial was conducted. The target population was pharmacists working in the Northern region
    of Portugal.

    Results
    The intervention resulted in a three-fold increase in the ADR reporting rate (RR = 3,22; 95% CI 95%: 1,33-7,80) when
                                                                                                                                 15
    compared to the control group, during the study period. In addition, the relevance of the ADR being reported also
    increased.
    Serious ADR reports increased 4-fold (RR = 3,87; 95% CI: 1,29-11,61) and unexpected ADR reports increased 5-fold (RR =
    5,02; 95% CI: 1,33-18,93), compared with the control group.

    Conclusions
    Educational interventions are efficient in increasing spontaneous ADR reporting rates, among Portuguese pharmacists.
    Workshops are as efficient as telephone interviews to improve ADR spontaneous reporting.
16
                                                                                     Utrecht   I WHO Winter Meeting 2010

                                             Lifestyle drugs and the reporting of psychiatric adverse
3                                                                 events in randomised clinical trials

                                                M.J.C. Willemen(1, 2), A.K. Mantel-Teeuwisse(1, 2), S.M.J.M. Straus(2),,
                                                                             H.G.M. Leufkens(1, 2), A.C.G. Egberts(1, 3)
                                                                                     1 Utrecht University, The Netherlands
                                                               2 Medicines Evaluation Board, The Hague, The Netherlands
                                                                     3 University Medical Center Utrecht, The Netherlands




    Rationale
    In the previous decade several lifestyle drugs were launched including Zyban®, Champix® and Acomplia®. Although
    differences exist in working mechanism and user population, these drugs are associated with psychiatric adverse events
    (AEs) [3-5]. In general, the methods for the collection of adverse events and the scales used to measure (psychiatric)
    AEs and the way the data were presented differ largely between randomised clinical trials [RCTs]. This may affect the
    interpretation of the data and makes a direct comparison of the results difficult, which can have implications for clinical
    and regulatory decision-making.

    Objective
    To assess how psychiatric adverse events are reported in RCTs, and to identify and quantify differences between studies
    regarding the reporting of psychiatric adverse events and patient characteristics.

    Methods
    A descriptive, cross-sectional study is designed. A systematic search will be performed using the database of the Dutch
                                                                                                                                      17
    Medicines Evaluation Board to identify the full clinical study reports for the RCTs with bupropion, varenicline and rimonabant.
    Information on the following variables will be extracted: date of study report, study location, outcomes of the studies,
    number of included patients, in- and exclusion criteria especially regarding psychiatric comorbidities, medical history of
    study participants, including psychiatric disease at baseline, measurement scales used to assess psychiatric disease (both
    at baseline and during follow-up) and methods used for the collection of AEs. Descriptive statistics will be applied to
    present the data.
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                                                                                   Utrecht   I WHO Winter Meeting 2010

                                                   The Impact of Periodic Safety Update Reporting on
4                                                                  Safety-Related Regulatory Actions

                      Ebbers, H.C., Mantel-Teeuwisse A.K., Moors E.H.M., Leufkens H.G.M., Schellekens H.
                                                                                        Utrecht University, The Netherlands




    Background
    A periodic safety update report (PSUR) provides an update of the worldwide safety experience of a pharmaceutical. PSURs
    are composed by marketing authorization holders and submitted to regulatory authorities on predetermined time points.
    It has been debated if periodic safety reporting is an effective tool to generate new safety signals. Furthermore, it is
    questioned if the obligation for PSUR reporting should be differentiated between products. However, information is lacking
    on how PSUR evaluations contribute to safety related regulatory actions. ---

    Objective
    The objective of our study is to analyze how PSURs contribute to the initiation of safety related regulatory actions.

    Methods
    We will perform a retrospective analysis of biological products registered in the European Union for which a safety-related
    Direct Healthcare Professional Communication (DHPC) was issued. An analysis of the role of PSUR evaluation in the
    initiation of safety associated regulatory actions will be performed through an analysis of data available in the public
    domain (e.g. DHPC itself, EMEA website) and the minutes of the Pharmacovigilance Working Party. Using the minutes and
    taking the time of the DHPC as a starting point, we will retrospectively determine a) the information that led to the DHPC
    in relation to a product, b) the initial identification of a possible relation between the event and the product. For both
                                                                                                                                  19
    these events we will determine when and how PSUR assessments were involved.

    Preliminary results
    From 1998-2009, we have identified 22 safety associated DHPCs within the European Union, relating to 14 biological
    products. None of the DHPCs made reference to PSUR evaluations. 4 safety related regulatory actions, relating to 2
    products referred to PSUR evaluations in the European Public Assessment Reports (EPAR).
20
                                                                                     Utrecht   I WHO Winter Meeting 2010

                                                                    Therapeutic indications in oncology:
5                                                             emerging features and regulatory dynamics

                                                          G. Tafuri       , H.G.M. Leufkens
                                                                      (1,2)
                                                                                                    , R. Laing
                                                                                                (2,3)
                                                                                                                   , F. Trotta
                                                                                                                 (4)             (1)

                                                                                  1. Italian Medicines Agency (AIFA) Rome, Italy
                                                                                            2. Utrecht University, The Netherlands
                                                                    3. Medicines Evaluation Board, The Hague, The Netherlands
                                                                             4. World Health Organization, Geneva, Switzerland




    Background
    The regulatory route leading to the definition of therapeutic indications of new compounds as well as extensions of
    indication (EoI) of already approved ones is a challenging process. If new anticancer drugs reach the market with a lack
    of complete evidence, this usually leads regulators to request additional data, post approval commitments or restrictions
    in therapeutic indications.

    Objectives
    This study aims at quantifying the time needed for anticancer drugs approved by the European Medicines Agency (EMEA)
    to get an extension, the rates and characteristics of extensions approved, and at exploring the regulatory process leading
    to the definition of new indications.

    Methods
    Information on regulatory steps leading to the definition of therapeutic indications for the cohort of anticancer drugs
    was extracted from the European Public Assessment Reports, publicly available on the EMEA website. Documents were
                                                                                                                                       21
    surveyed for new applications as well as for later extensions between January 1995, when the EMEA was set up, and
    December 2008.

    Results
    A total of 103 therapeutic oncological indications, related to a cohort of 43 anticancer drugs, were retrieved between 1995
    and 2008. The median time occurring between different indications for the same compound (defined as Time to New
    Extension, TtNE) significantly decreased from about 81 months in 1996 up to 6 months in 2006. Twenty-four out of 43
    approved anticancer medicines (about 56%) have only a single therapeutic indication, 12 of which were approved before
    2005.
    When considering two different cohorts of drugs in relation to the time of approval (1995-2004 versus 2005-2008),
    although not statistically significant, the older cohort tended to have a decreased probability of having EoI when compared
    to the new cohort (OR=0.27; 95% CI: 0.07-1.04). With regard to the type of EoI (n=60), our findings showed that in 48%
    of cases the initially approved indication was extended to treat a different tumour, in 37% of cases the extension consisted
    in a switch of line within the same therapeutic indication. The other two types of indication broadening refer to a different
    tumour stage (8%) and to the inclusion of a new patients population (7%).
    The analysis of indication restrictions showed that in 20 cases out of 50 (40%) therapeutic indications were restricted by
    the Committee for Medicinal Products for Human Use of the EMEA during the assessment, with 60% of the restrictions
    occurring in 2006-2007.

    Conclusions
    This study adds three main pieces of information: i) the majority of anticancer drugs still has a single indication regardless
    of the year of approval; ii) the time needed to obtain an extension of indication has decreased significantly over the last
    decade; iii) the highest rate of regulatory restrictions is matched to shorter clinical developments.
22
                                                                                    Utrecht   I WHO Winter Meeting 2010

                          Medicines promotion: Assessing the scope and impact of regulation
6
                                                                                                                      C. Piriou
                                                                                      HAI Europe, Amsterdam, The Netherlands




    Rationale
    Medicines play an important part in health care. However, irrational prescribing and use often result in inappropriate or
    harmful treatment, a waste of resources and increased drug resistance. As a result, many countries have introduced a
    legislative framework to regulate the promotional activities of the pharmaceutical industry, but they vary widely regarding
    content, implementation and enforcement. In developing countries especially, overstretched health systems may have
    difficulties allocating sufficient resources to regulate promotion.

    Objectives
    The project will determine the scope of regulation on pharmaceutical promotion in countries and the impact of the
    regulatory framework on promotional practices.

    Methods
    HAI’s research tool combines desk research, interviews and data collection to provide a complete picture of the national
    situation. It will include an analysis of relevant laws, guidelines or codes related to medicines promotion, an assessment of
    mechanisms for enforcement, key informant interviews for in-depth analysis of the situation and measurement of specific
    promotion outcomes (such as direct-to-consumer advertisements, sales representatives practices, generics use...)

    Expected outcomes
                                                                                                                                    23
    The research tool should provide country profiles concerning promotion. It will highlight the strengths and weaknesses
    of the regulatory framework, the outstanding enforcement issues and provide understanding of the political context and
    stakeholders’ positions regarding regulation. The findings will reveal examples of best practices which could provide a
    model for other countries. National surveys carried out should provide an evidence base upon which countries can make
    policy choices to improve the use of medicines.
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                                                                                       Utrecht   I WHO Winter Meeting 2010

                       What is growing in the area of Advanced therapy medicinal products?
7                       Bridging the ATMP clinical pipeline to the EU regulatory framework

                                                                                                                         R. Bruno
                                                                                            Utrecht University, The Netherlands




    Background
    The new European Regulation 1394/2007 on Advanced Therapy Medicinal Product recently entered into force. ATMPs are
    somatic cell medicinal products, gene therapy medicinal products and tissue engineered products.

    Objective
    Analysis of the current situation of gene, cell and tissue products under clinical development to build a taxonomy of
    the ATMP clinical pipeline: identification of potential candidates for a MAA in Europe and/or for exemptions under the
    Regulation 1394/2007.

    Methods
    For the selection of relevant clinical trials, the website clinicaltrials.gov was used, setting the filters: ‘interventional’
    studies, phase ‘I- II-III’, funded by ‘Industry’ and ‘University/Organization’, registered/updated in the time frame ‘January 1st
    2007 - 31st August 2009’. Resulting trials were screened to identify potential ATMPs. Products included were classified per
    sponsor type, anatomical application and then into subcategories based upon the principal technology/mode of action.

    Results
    A total of 231 products could be identified as ATMP from the selected database: 161 from the ‘Industry’ pipeline (20% SC,
                                                                                                                                        25
    57% GT and 23% TE) and 70 sponsored by EU ‘Universities/Other organization’ (31% SC, 16% GT and 53% TE).

    Conclusion
    ATMP sector is growing and general trends are identifiable in the pipeline: ‘Antineoplastic and immunomodulating agents’
    and ‘Cardiovascular system’ are the main categories; differences between industrial and academic sponsors exist. Application
    of specific articles and definitions of the new regulatory setting can be discussed on the basis of these results.
26
                                                                                    Utrecht   I WHO Winter Meeting 2010

                                      Scientific Advice in the marketing authorization procedure:
8                                                               A Cross-sectional Content Analysis

                             M. Putzeist     , A.K. Mantel
                                           (1)
                                                                   , C.C. Gispen
                                                               (1,2)
                                                                                     , A.W. Hoes
                                                                                   (2)
                                                                                                      , H.M.G. Leufkens (1,2)
                                                                                                    (3)

                                            1. Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands
                                                                      2. Medicines Evaluation Board, The Hague, The Netherlands
                             3. Julius Centre for Health Sciences and Primary Care, University Medical Centre, The Netherlands




    This study will be performed in the context of the Escher project (T6-202), a project of the Dutch Top Institute Pharma.

    Scientific advice is aimed at creating the opportunity of communication between sponsors and registration authorities
    about all aspects of drug development. This type of regulatory dialogue should facilitate drug development. Both national
    registration authorities and the European Medicines Evaluation Board (EMEA) provide scientific advice to sponsors.
    Little is known about the questions asked by sponsors and answers provided by registration authorities. Therefore, the
    primary aim is to describe the main characteristics and content of scientific advice to learn about its role in facilitating
    drug development. Secondary, potential relations between type of drug and company and content of questions will be
    identified.
    A descriptive cross-sectional content analysis was implemented of all scientific advice provided by the Dutch Medicines
    Evaluation Board in 2006, 2007 and 2008. ATC-code and type of company were collected for each advice. Companies were
    defined ‘Small and Medium Sized Entities’ if present on the official EMEA-list of SMEs, October 2009. The content of each
    question and answer was scored separately.
                                                                                                                                    27
    In three years scientific advice was given 201 times. In total 1084 questions and 1084 answers were described. Advice
    was most frequently asked for Nervous system drugs (46 times). Large companies asked advice 186 times (in total 122
    companies), while SME’s asked for advice 15 times (13 companies). On average 5.4 questions were asked per advice. The
    average number of questions did not differ significantly between large companies and SME’s (p = 0, 803).
    In total 71.2% of all questions were clinical. Of these clinical questions 15.5% discussed efficacy endpoints. Large
    companies and SMEs did not differ significantly with regard to number of questions about efficacy endpoints (p= 0,953).
    In subsequent analyses more relations with regard to content of scientific advice will be studied.
28
                                                                                   Utrecht   I WHO Winter Meeting 2010

                                              Assessing patient and consumer input into the review
9                                                            of medicines’ information at the EMEA

                                                                  T. Alves, A.K. Mantel-Teeuwisse, H.G.M. Leufkens
                                                                                             Utrecht University, The Netherlands




    Nature of research
    Early-stage project; input is required to optimize the study design and strengthen methods. Preliminary results of the pre-
    testing will be presented and further discussed.

    Rationale
    The European Medicines Agency (EMEA) is responsible for approving and preparing specific medicines’ information to be
    disseminated to the public. Since 2007 patient and consumer organisations eligible to work with the EMEA are invited
    to review patient information leaflets and summaries of the European Periodic Assessment Report (EPAR) for centrally
    approved products. The aim is to improve the adequacy and readability of the information being provided. Each document
    is allocated to a specific organisation according to its expertise. Recommendations for change are then examined by the
    EMEA and eventually accepted or rejected. Till date, no external assessment of this patient and consumer review process
    has taken place.

    Objective
    To investigate the implementation rate of changes to medicines’ information documents being proposed by patient and
    consumer organisations to the European Medicines Agency; to study the association, if any, between several factors and
    change implementation.
                                                                                                                                   29

    Proposed Methods
    Study design: Prospective study over 12 months. (By October 2009, 49 documents out of a total of 95 sent, had received
    recommendations for changes).

    Inclusion criteria: All documents sent for review within the 12 months of the study period.

    Organisations will be invited to join the study on a voluntary basis and to complete each review by filling in a data-
    collection tool. The data-collection tool will enable coding of the changes or comments into different categories.

    Potential associations between several factors (i.e. type of change, type of document, reviewer organisation, therapeutic
    class) and adoption in the final document will be assessed through regression analysis.
30
                                                                                     Utrecht   I WHO Winter Meeting 2010

                                                Drug Life Cycles as a Tool in Drug Regulation:
10                     The Case of Selective Serotonin Reuptake Inhibitors (SSRIs) and Safety

                                             F. Hernandez, A.K. Mantel-Teeuwisse, J.A.M. Raaijmakers, T. Pieters
                                                                                Division Utrecht University, The Netherlands




     Through a series of product-cry-outs during the last decades, public trust in the making and taking of pharmaceuticals
     has been tainted. As a result both the pharmaceutical industry and regulatory agencies are under public scrutiny for
     the governance of pharmaceuticals. There is a necessity for a sustainable drug regulatory system that will add to a
     trustfully infrastructure between society, industry and agencies. We hypothesise that drug life cycle (DLC) analyses
     may serve as a tool to strengthen regulatory policies, improving the understanding of the dynamics of the societal
     embedding of pharmaceuticals. DLC studies may provide a framework, whereby crucial interventions and interfaces could
     be pinpointed.

     In this study we analyze actors and factors that might generate fluctuations on a DLC. The quantification of the various
     factors and relationships under survey is challenging. Several domains (science, medicine, industry, and the public sphere)
     will be investigated through pharmacoepidemiological methodology within the scientific literature (Pubmed and Embase),
     media (LexisNexis), and sales and prescription patterns (IMS). Thus, an attempt will be made to analyze product dynamics
     in the pharmaceutical market place. For this study, a product-cry-out was selected, i.e. SSRIs and suicidality, to enable the
     analysis of the SSRI safety controversy and establish relationships between the various domains under survey. Data will
     be obtained over the period 1st January 1990 to 31st October 2009 for the Netherlands and the UK.

     We observed an increasing trend in the number of articles within the scientific literature and newspapers along the years.
                                                                                                                                     31
     It was also discerned that crucial events or polemic discussions in both fields might be reflected in the number and the
     nature of the articles in the medical literature and the newspapers. However, a direct causality has not been established
     so far.

     The study of product-cry-outs as well as early drug promises through DLC analyses may enrich the understanding of the
     societal embedding of drugs. This in turn may help to maintain a sustainable drug system, and a transparent contract
     between society, agencies and industry.
32
                                                                                     Utrecht   I WHO Winter Meeting 2010

              Under the Influence: Association between corporate sponsorship and policy
11                            perspectives of Pan-European patient and consumer groups

                                                                                                         Katrina Perehudoff
                                                     NIVEL (Netherlands Institute for Health Services Research), Utrecht,
                                                                                                        The Netherlands




     Rationale
     Patient organisations are trusted to champion patients’ best interests through reliable, good quality health information and
     services, provided to the public, patients, and policy makers.
     Pharmaceutical companies routinely fund patient organisations on the basis of their shared interests in therapy or disease
     treatment. Corporate agendas could influence patient groups’ public and political messages through funding relationships.
     Messages can be given greater legitimacy and attention in public and political arenas when delivered by patients and
     users, and so, the integrity of decision making on medicines policy and public health could be jeopardised.

     Objective
     To investigate the association, if any, between Pan-European patient and consumer (P&C) organisations and the
     pharmaceutical industry.

     Methods
     A questionnaire was developed to adjudicate the degree to which P&C groups’ policy positions are aligned with public
     health interests. The questionnaire includes 30 statements about the Pharmaceutical Package, a package of three proposals
     to change European legislation on medicines, based on established stakeholder positions. The content was reviewed by
                                                                                                                                    33
     an expert committee. Each P&C organizations eligible to work with the European Medicines Agency (inclusion criteria) was
     invited to indicate its degree of alignment with each statement using Lickert scaling.

     Next Steps
     The questionnaire will also be completed by blinded third parties based on coding and analysis of published policy
     documents from each P&C group.
     Both types of survey responses (self-administered and blinded third party) will be paired with the level of corporate
     funding of each organisation, in order to determine if any association exists between the two.
34
                              Utrecht   I WHO Winter Meeting 2010

     Accelerating Dosage Revisions of Newly Approved Drugs
12
                                                     M.R. Crombag
                                  Utrecht University, The Netherlands




                                                                        35
36
                                                                                   Utrecht   I WHO Winter Meeting 2010

                                              Household medicines use in Ghana: a quantitative and
13                                                       qualitative exploration into a dual system

                                                                                                                      A. Sato
                                                                                London School of Economics, United Kingdom




     Introduction
     Medicines expenditure constitutes a significant proportion of total health spending in developing countries. Realising
     this, the UK Department for International Development (Dfid) and WHO have been leading players in the Medicines
     Transparency Alliance (MeTA) initiative, which seeks to curb corruption, and increase transparency and accountability in
     the health sector - in particular within pharmaceuticals - in developing countries. My research hones in on an element
     within this initiative, namely the demand and utilisation of medicines by households in Ghana (a pilot country in the MeTA
     initiative), and further extends this by looking at the parallel, or dual, system of traditional medicines use.

     Objectives
     To explore treatment choice pathways of medical institutions in Ghana, both in terms of western medicines and traditional
     medicines. To quantify traditional medicines use.

     Methods
     Quantitative and qualitative methods: medicines use household questionnaire; nested multinomial logit modelling, in
     depth interviews


                                                                                                                                  37
38
                                                                                      Utrecht   I WHO Winter Meeting 2010

                       Utilisation of patient assessment and pill-count data in understanding
14                                    adherence to antiretroviral therapy in Uganda’s settings

                                                                                                                    A. Ssewaya
                                            Amsterdam School for Social Research (ASSR), Amsterdam, The Netherlands




     Rationale
     As part of MIS for HIV/AIDS treatment, ART accredited sites in Uganda collect comprehensive data concerning patients’
     profile, clinical conditions, adherence to treatment activities, and adherence barriers. While such existing data can feed
     into monitoring and evaluating of HIV/AIDS treatment programme, they are scarcely used to that effect.

     Objectives
     The objective of this exercise was to make use the existing HIV/AIDS treatment data in deriving retrospective adherence
     patterns and health outcomes, as a basis for designing adherence best practices for the two sampled ART sites in
     Uganda.

     Methods
     Patients’ assessment and pill-count data were collected from 262 patients’ files, integrated into structured survey
     questionnaire, and that data verified with patients at the time of interview. The extraction process captured the previous
     date of entry in order to derive trends-analysis. Cross-sectional and longitudinal analyses were carried in order to establish
     patients’ characteristics; adherence to treatment initiation activities, pharmacy refill, and medication dose; occurrence of
     biomedical and socio-economic barriers; and changes in health indicators (i.e. CD4 count, weight, functional status, and
     WHO-staging).
                                                                                                                                      39

     Key Lessons Learnt
     Patient’s files can be a source of fairly accurate data for understanding adherence to ART and health outcomes, as well
     as guiding treatment interventions. In this study, the observed seasonal variations in adherence due to multiple barriers,
     calls for intensification of adherence support programme during given months of the year.
40
                                                                                      Utrecht   I WHO Winter Meeting 2010

                                  A descriptive report on the first hundred HIV/AIDS cases on
15                      antiretroviral therapy at the Korle-Bu teaching hospital, Accra, Ghana

                                                                                                                      D. Ankrah
                                                                                           Korle-Bu Teaching Hospital, Ghana




     Introduction
     Although the first case of Acquired Immune Deficiency Syndrome (AIDS) was reported in Ghana in 1986, it was not until
     June 2003 that antiretroviral therapy (ART) in the public health care system started. This implies that any patient who was
     put on ART before June, 2003 had to buy from private sources at an unsubsidized price.
     HIV related drug resistance, disease progression and death can all be reduced when there is proper adherence to ART
     treatment.

     Objectives
     To:
     • Examine the baseline characteristics of the first hundred HIV/AIDS adult patients (>=15 years) who were treated with
         antiretroviral medicines.
     • Examine the behaviour of these patients during follow-up.

     Methodology
     Data were collected from the Fevers Unit of the KBTH where records for all HIV/AIDS patients 14years and above are kept.
     This was after permission was granted by the consultant physician in charge of the Unit. Baseline characteristics were
     collected using the “initial patient assessment (client record)” form. Data on follow-up issues was assessed from the
                                                                                                                                      41
     “registration (clinical care) booklet”. Data collected was cross-checked with pharmacy records in the patient folder. Analysis
     was done using Stata intercooled version 9.1.

     Results
     There were 62 (62%) women. At baseline 40% of participants were on Combivir and Nevirapine; 38% used Combivir and
     Efavirenz; 12% used Stavudine, Lamivudine and Nevirapine; 9% used Stavudine, Lamivudine and Efavirenz; 1% used
     Combivir and Nelfinavir. At the end of follow-up (31st August, 2009) five deaths were recorded.

     Limitation
     Missing values formed about 17% of some variables.
42
                                                                                    Utrecht   I WHO Winter Meeting 2010

                                             Assessing the Ghanaian Public Health Sector Medicines
16                                                   Procurement and Supply Management Systems

                                      M. Gyansa-Lutterodt(1), B. Adu Asare, E. Andrews-Annan(2), I. Agyepong(3)
                                                                                      (1) Ghana National Drugs Program, Ghana
                                                                           (2) World Health Organisation Country Office, Ghana
                                                                       (3) Greater Accra Regional Health Administration, Ghana




     The Pharmaceutical procurement system is a major determinant of drug availability and total health costs. One major
     challenge of National Medicines Policy is assuring an interrupted supply of essential medicines that are efficacious and of
     good quality, physically and financially accessible and used rationally.

     Objectives:
     • To determine the strengths and weaknesses of existing medicines supply systems and to propose recommendations
       and strategies on how to improve them.
     • To develop a coordinated, coherent and efficient national medicines supply plan or strategy.

     Method
     This assessment compared the current management arrangements in handling pharmaceuticals within the tiers of the
     system; analysed the policy environment in which the supply chain operated; examined the tools and procedures used
     in such varied tasks as quantification, inventory and information management. It also assessed the current purchase
     prices and availability of a basket/tracer pharmaceuticals comparing local and international prices and analysed margins;
     diagnosed the management information systems and human resource gaps affecting the supply chain and the impact of
                                                                                                                                   43
     monitoring and evaluation on the performance of the supply chain.

     Results
     This study identified challenges in product selection, quantification and forecasting, general procurement, distribution,
     monitoring and evaluation and human capacity and made recommendations.
44
                                                                                   Utrecht   I WHO Winter Meeting 2010

                          Review of risk sharing schemes for pharmaceuticals: considerations,
17                             critical evaluation and recommendations for European payers

                        J Adamski, B Godman, G Ofierska-Sujkowska, H Herholz, K Wendykowska, O Laius,
                                                      S Jan, A Haycox, R Gustafsson, and L L Gustafsson
                                                                                                  Ministry of Health, Poland




     Background
     Governments and health authorities are increasingly considering ‘risk sharing’ schemes as one way to provide continued
     comprehensive and equitable healthcare in Europe. There is though confusion surrounding current terminology as well as
     concerns with existing schemes.

     Methods
     An extensive literature review was undertaken supplemented with internal documents or web-based references known to
     the authors combined with their extensive knowledge of ongoing schemes.

     Results and discussion
     A large number of ‘risk sharing’ schemes are in existence incorporating both financial-based models and outcome/
     performance based models. In view of this, a new working definition is proposed - ‘risk sharing’ schemes should be
     considered as agreements concluded by payers and pharmaceutical companies to diminish the impact on payers’ budgets
     for new and existing schemes brought about by uncertainty and/ or the need to work within finite budgets. There are
     a number of concerns with existing schemes which include potentially high administration costs, lack of transparency,
     long length of follow-up in some, whether health authorities will end up funding a significant proportion of a new drug’s
                                                                                                                                  45
     development costs, and whether pharmaceutical companies will over price new drugs initially in anticipation of price cuts
     down stream. Potential ways to address these concerns are proposed including factors that should be considered by payers
     in advance to enhance successful implementation. This includes their appropriateness, level of evidence, transparency, the
     availability of competent evaluating staff, funding including IT support as well as evaluation built in up front.
46
                                                                                     Utrecht   I WHO Winter Meeting 2010

                                               Reforming the medicine prescribing practices in SEE:
18                                        case of policy and implementation changes in Macedonia

                                                                                       N. Milevska-Kostova(1), M. Gulija(2)
                1. University of Sheffield, UK and Centre for Regional Policy Research and Cooperation ‘Studiorum’, Macedonia
                                              2. University of Zagreb, Croatia and Health Insurance Fund, Republic of Macedonia




     In transition economies, where governments have decided to employ the privatization and concessions mechanisms for
     increasing efficiency of the healthcare system, the potentials for supplier-induced demand (SID) have been considered
     higher, due to the enabling environment for profit-making. More so is the case with the pharmaceuticals supply, which
     represent 20-40% of THE, as prescribing a drug is one of the most frequent therapeutic decisions by GPs (Bakker, 2007),
     representing focal point of contact between doctors and patients and one of the indicators of quality of medical care
     (Harding, 1985).
     This paper aims to explore the effects of changing the incentive system for primary healthcare providers and pharmacists
     on the level of prescription and demand for medications in transition economies of SEE, with Macedonia as case study.
     The specific objectives are: exploring the effects of limiting the number of prescriptions per patient and the reinforcement
     of prescription mechanisms on the overall prescription of and spending on medications.
     A mixed method approach is used, combining quantitative and qualitative research methods. There is a well-established
     body of knowledge about mixed methods research (Brannen 1992, Bryman 2006), especially suitable for addressing wider
     questions than quantitative methods alone would allow (O’Cathain et al. 2007).
     Selected drug groups have been analyzed, especially those that have proven health and societal implications if taken
     without prescription as control mechanism (Laux&Puryear, 1984; O’Brien, 2005).
     The preliminary results show positive correlation of policy changes with prescription leveles. The model can be applied for
                                                                                                                                    47
     other drug groups and other countries struggling with similar policy and implementation issues.
48
                                                                                    Utrecht   I WHO Winter Meeting 2010

                                                  Is evaluation of the cost-benefit of drugs feasible? –
19                                                               Current developments in Switzerland

                                                                                                                   S. Dagron
                                                                                            University of Zurich, Switzerland




     Rationale
     Regulations concerning the pharmaceutical industry’s pricing and the need to prove efficacy have been remarkably liberal
     in most countries. Different European countries have recently adopted strategies to implement a rational use of drugs.
     In France, Germany and the United Kingdom, institutions such as HAS, IQWIG and NICE have been entrusted with an
     appreciation of empirical data regarding the efficacy and cost-benefit of pharmaceuticals. They issue recommendations
     which are taken into account for the reimbursement of drugs. In Switzerland the Canton of Zurich has started a pilot
     project by entrusting a Medical Board for a certain period of time with similar tasks. The implementation of a permanent
     institution is currently a matter of debate.

     Objective
     Our research aims at identifying the legal problems and questions attached to regulations concerning the reimbursement
     of drugs. On the basis of the analysis of different national models (with a particular emphasis on institutional structures
     and administrative procedures) the paper will close with some reflections and suggestions regarding the implementation
     of a regulatory policy in Switzerland.

     Method
     The analysis of national cases is controversial since national states have different administrative traditions and rules.
                                                                                                                                   49
     However, we argue that common constitutional principles like rule of law and democratic legitimation guide the development
     of administrative law. Thus, national experiences in the field of administrative law can be fruitfully analyzed for the
     implementation or modernization of policies in other countries.
50
                                                                                    Utrecht   I WHO Winter Meeting 2010

                                  How much of the price variance of medicines can be explained
20                                                         by national pharmaceutical polices?

                                     C. Leopold(1), S. Vogler(1), R. Laing(2), A. Mantel-Teeuwisse(3), B. Leufkens(3)
                                  1. Health Economics, Gesundheit Österreich GmbH Austrian Health Institute, Austria,
                                                                           2. World Health Organization, Switzerland
                                                                               3. Utrecht University, The Netherlands




     Background
     National pharmaceutical polices are embedded in an international as well as European framework. Within these settings
     countries have to decide how to guarantee its population an equal and affordable access to medicines. Taking into
     account that the economic situation of the EU Member States vary to a great extent, they still all have to cope with the
     same challenge of scare resources. Hence, this leads to different policy decisions influencing, among others, the prices of
     medicines. This results in a great price variance among countries.

     Methods
     In a cross-sectional analysis the price of an original product is compared at all three price types in five countries (AT,
     NL, NO, PT and SK) over a period of three years (2007 – 2009). The underlying price differences are analyzed, taking in
     consideration various independent variables such as the overall pharmaceutical framework.

     Results/Conclusions
     First preliminary results show, that those five countries have quite different pharmaceutical policy approaches.
     The price comparison shows that there is a huge price difference among all three price types and among all five countries.
                                                                                                                                   51
     One of the variables that may explain those price differences are the wholesale and pharmacy mark-ups. Another relevant
     component that has a great influence on the price is the taxation policy of a country. Reimbursement decisions have also
     a great influence on the price setting of a pharmaceutical. In terms of equal access and affordability the co-payment rate
     is also important to consider.
52
                                                                                     Utrecht   I WHO Winter Meeting 2010

                                         Is the UNITAID Patent Pool Initiative Making a Difference?
21
                                                                                                                    W. Kaplan
                                                                 Boston University School of Public Health, United States




     Nature of research
     Patent pools are a way of collectively managing intellectual property (IP). The most prominent recent patent pools have
     been in the IT field in which an industry standard (e.g., for DVD disks or video compression technology) is created and
     various patents are placed into the pool so that multiple, blocking patents can be licensed as a “package”.

     The UNITAID Patent Pool lnitiative creates such a collective management structure for anti-retroviral (ARV) medicines.
     Entities licensing IP are generic pharmaceutical companies. The objective is to improve ARV access by creating ‘downstream’
     competition among generic companies. This should lead to lower ARV prices. This business model requires careful
     monitoring to determine if ARVs will behave according to the Pool’s objective.

     Objective
     To determine if the UNITAID Patent Pool Initiative will succeed in lowering prices for first and second line ARVs.

     Methods
     We envision a time series starting from early 2009 and continuing across and for several years beyond a “policy threshold”-
     defined by the beginning of license negotiations for the Pool Initiative (to begin possibly as early as January 2010). The
     publicly available Global Price Reporting Mechanism dataset and IMS data will be used to track prices and volumes of
     ARVs in the public and private sectors. Analysing an ideal “control” series of medicines may be problematic. Possibly,
                                                                                                                                   53
     these would include medicines for opportunistic infections associated with HIV/AIDS but not part of the “pool”. A “control”
     might also include second line and therefore expensive ARVs not part of the pool.
54
                                                                                      Utrecht   I WHO Winter Meeting 2010

            A study on the uptake of TNF inhibitors in different European Member States
22
                    J.M. Hoebert       , A.K. Mantel-Teeuwisse
                                     (1)
                                                                        , L. van Dijk
                                                                      (1)
                                                                                           , R. Laing
                                                                                         (2)
                                                                                                          , H.M.G. Leufkens
                                                                                                        (3)                      (1)

                                                                                        1. Utrecht University, The Netherlands
                                                                                           2. NIVEL, Utrecht, The Netherlands
                                                                                    3. World Health Organization, Switzerland




     Background
     Drug use varies between countries for lots of reasons, e.g. related to policy decisions. For the anti-TNF agents, infliximab,
     etanercept and adalimumab, this may be even more the case as these drugs are effective, but expensive. Not only
     regulators, but also formulary commissions in hospitals have to decide about the uptake of these drugs. Actual drug
     consumption for TNF inhibitors within the framework of an international comparison has not previously been studied.

     Aim
     To explore whether a country based comparison of the use of TNF inhibitors in the EU is possible with the available data
     and to assess if specific policy characteristics related to TNF inhibitors are associated with the level of TNF inhibitors
     utilisation.

     Methods
     For this study two different types of data were collected from six EU member states (Denmark, Finland, Ireland, The
     Netherlands, Norway and Portugal): a. quantitative utilization data and b. qualitative data on policy measures, guideline
     preferences and supply side measures by means of a questionnaire filled in by country representatives. Utilization data
                                                                                                                                       55
     (DDDs/1000inhabitants/day) were extracted for products within the WHO ATC class L04AB01, L04AB02 and L04AB04 for
     the period 2002 to 2007.

     Results
     Five countries provided dispensing data and one country used reimbursement data to capture drug utilization. A
     differentiation between sales to in- or outpatient health care centers was available for four countries. All countries provided
     data that covered more than 98% of the total population. For all countries an increase in use over time was observed.
     The utilisation of all TNF inhibitors for the year 2006, the most recent year for which data were available for all countries,
     varied strongly from 0.25 DDDs/1000inh/day for Portugal to 1.89 DDDs/1000inh/day for Norway.

     Conclusion
     A large variation in utilisation of all TNF inhibitors was observed. This variation can be partly explained by differences in
     the setting where these drugs are used (in- and outpatient use) and ways of distribution.
56
                                                                                 Utrecht   I WHO Winter Meeting 2010

                                                  Medicine consumption and expenditure databases’
23                                                           analysis as the basis for policy changes

                                                                                           L.E. Ziganshina, R.R. Nyazov
                                                          Kazan State Medical Academy; Federal State Research Centre
                                                                         for Evaluation of Medicinal Products, Russia




     The database of 130.3 million prescriptions for 6.2 million participants of the Government provided Nation-wide
     Complementary Medicines Supply Programme (2006) was made available for our research by the Federal Fund of Obligatory
     Medical Insurance (Moscow) on the grounds of contractual agreement.

     We used WHO Medicine use indicators (4 prescription indicators), ATC/DDD and ABC/VEN methodologies; we analysed
     consumption of brands versus generics, of locally produced versus imported medicines, and against the WHO Model List
     of Essential Medicines. These methods were adapted to computer assisted processing of massive databases.

     We revealed disproportion between expenses for essential and non-essential medicines. Prescribers preferred the most
     expensive aggressively promoted medicines while cheaper alternatives were available. The consumption of cardio-vascular
     medicines was the highest. The anticancer medicines and immunomodulators accounted for the top expenses due to high
     prices, not to consumption. Consumption of ineffective medicines, medicines with uncertain effects, unduly expensive
     medicines was inappropriately high.
     On the basis of these results recommendations on improvement of the Programme were developed. These were partially
     taken into account in the Programme development in 2008: exclusion of some of inappropriate medicines from the
     Programme Medicines list and establishment of a requirement to endorse prescription of certain expensive medicines by
                                                                                                                               57
     expert groups. The process of revision of the Federal Essential Medicines List has been initiated; the new version will
     become available in 2010.
58
                                                                                      Utrecht   I WHO Winter Meeting 2010

                                 Impact of economic recession on the consumption of medicines.
24                                                                    An analysis on ATC-2 level

                                                              I.M. Buysse       , R.O. Laing
                                                                              (1)
                                                                                                  , A.K. Mantel-Teeuwisse(1)
                                                                                                (2)

                                                                                        1. Utrecht University, The Netherlands
                                                                                    2. World Health Organization, Switzerland




     Background
     In January 2009 WHO was requested to investigate the impact of the current economic recession on health. The
     pharmaceutical consumption was investigated in 83 countries, which showed that only some countries had a decline in
     pharmaceutical consumption since start of recession in Q1 2008. To explore what is going on in these countries it would
     be interesting to assess these changes in consumption in more detail.

     Objective
     The goal of this study is to investigate which medicines are affected the most and the least by this recession in terms of
     decline in consumption in countries that seem to be affected most by the recession.

     Methods
     IMS Health provided a dataset which contained the supply units per ATC-2 category for six selected countries (Estonia,
     Latvia, Lithuania, Romania, Poland and Mexico) for the period Q1 2007 to Q2 2009. Total supply units were calculated per
     quarter and supply units were expressed as a percentage of the total supply units of that corresponding quarter. Pareto
     analyses were performed to select the 30% of ATC2 categories that accounted for about 80% of total consumption.

                                                                                                                                     59
     For these 30% of ATC2 categories the total number of supply units for Q4 07 plus Q1 08 (last 2 quarters before recession)
     were compared with the total number supplied in Q4 08 and Q1 09 (during the recession). Similar periods in the calendar
     year were chosen to avoid changes in medicines consumption due to seasonal influences. The ATC2 categories were sorted
     by percentage change between the two periods after which a comparison was made between the different countries.

     Results
     Preliminary results show that 13 ATC2-categories declined in at least 3 countries which were hit by the recession. Major
     declines were observed for ATC2 categories that may not necessarily affect public health in a harmful way, e.g. A 11 Vitamins
     (-22,0% - -15,1%) and R1 Nasal preparations (-24,1% - -3,2%). However, declines were also observed for ATC2 categories for
     which a decline in more important categories such as M1 Antireumatics systemically (-20,6% - -0,3%), S1 Opthalmologicals
     (-20,2% - -0,0%), N5 Psycholeptics (-19,8% - -0,9%) and N2 Analgesics (-19,3% - -9,0%). Another interesting finding is that
     in Estonia all the ATC2 categories which accounted for 80% of the consumption were declining.
     Based on these results, we will try to identify a selection of possible marker products on ATC 3 and 4 level. Various
     methods to select these marker products are now being investigated.
60
                                                                                   Utrecht   I WHO Winter Meeting 2010

                                                                         The selection of essential medicines
25
                                                                                         R. van den Ham        , R. Laing
                                                                                                             (1)            (2)

                                                                                    1. Utrecht University, The Netherlands
                                                                                2. World Health Organization, Switzerland




     Essential medicines are defined as “those that satisfy the priority health care needs of the population” (…).[1] The WHO
     Model List of Essential Medicines (Model EML) serves as a model for countries to develop their own EML and to achieve
     better health care, better drug management and lower costs.

     Aim of the research project was to describe the evolution of the WHO Model EML over time (1977-2009) and to compare
     national EML’s and the WHO Model EML to verify in which way countries use the WHO Model List for their own decision
     making.

     Both the quantitative (e.g. number of molecules on the Model EML, number of formulations and dosages and their ratio)
     and qualitative changes (e.g. additions and deletions of specific molecules) between 1977 and 2009 were assessed. For
     comparison of the Model EML with national EML’s a selection of 12 EML’s from the year 2006 and 2007 was made and
     these lists were compared to the 2005 WHO Model EML.

     The WHO Model EML showed since 1977 an overall growth of 151 newly added molecules. Large differences were observed
     between the Model EML and national EML’s.

     The WHO Model list expanded between 1977-2009 mainly due to the growth of specific sections and the incorporation of
                                                                                                                                  61
     the Essential Medicines List for Children (EMLc). Differences between the Model EML and national EML’s were observed.
     Reasons for countries not to include specific medicines may be the variety in burden of disease costs, unavailability, or
     cultural unacceptability of the medicine.
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                                                                                      Utrecht   I WHO Winter Meeting 2010

                                     Differences in the availability and price of medicines used
26                          for chronic conditions compared to those used for acute conditions

                                                                      Cameron A.1, Roubos I.2, Ewen M.3, Laing R.O. 4.
                                      1. World Health Organization, Switzerland and Utrecht University, The Netherlands
                                                                                  2. Utrecht University, The Netherlands
                                                                         3. Health Action International, The Netherlands
                                                                              4. World Health Organization, Switzerland




     Rationale
     Developing countries undergoing an epidemiological transition from infectious and parasitic diseases to non-communicable
     diseases require health systems modifications to address the long-term nature of these diseases. Access to essential
     medicines should be a key component of the policy framework, however it is unknown to what extent governments are
     meeting the demand for the essential medicines used to treat chronic conditions.

     Several studies of the prices and availability of essential medicines have found that that low availability, high prices and
     poor affordability are key impediments to access to treatment in low- and middle-income countries. Research focused
     specifically on medicines used to treat chronic diseases have shown similar results, however a comparison between
     treatments for acute and chronic conditions has not been conducted.

     Objective and Methods
     The objective of the study is to assess whether differences exist in the availability of medicines used for chronic conditions
     compared to those used for acute conditions in low- and middle-income countries. Data on medicine availability were
                                                                                                                                      63
     obtained from facility-based surveys conducted in 40 developing countries using a standard methodology. Medicine
     availability were compared for 30 commonly-surveyed medicines; 15 used for acute conditions and 15 used for chronic
     diseases. Results were aggregated by World Bank Country Income Group and by WHO Region.

     Results
     Average results across the countries studied show that generics medicines used for chronic diseases have lower availability
     than those used for acute conditions in both the public sector (36.0% versus 53.5%, respectively) and private sector
     (54.7% versus 66.2%, respectively). This difference is inversely proportional to country income level; the lower the income
     level, the larger the gap in availability between the two treatment types.
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                                                                               Utrecht   I WHO Winter Meeting 2010


                                                                 Other abstracts – not to be presentedo


                                   Impact of Compulsory Licensing in Ecuador on medicines prices:
                                                An interrupted time series analysis using IMS data

                                                                        Kaplan W, Maybarduk P, Wirtz V, Trout C
                                                            Boston University School of Public Health, United States



Background
Ecuador’s private and public pharmaceutical markets comprise 87% and 13% , respectively, of the total value. Around
11.3% of volume sale are generic drugs. Foreign firms control 82% of the pharmaceutical market (IMS data). On 26
October 2009 the government of Ecuador announced that it will allow the use of Compulsory Licensing (CL) for medicines
patented in Ecuador in order to increase access to medicines. Evaluating whether the mere announcement, or the actual
use, of compulsory licensing impacts prices and/or the mix of available medicines is relevant to make judgments about
the effectiveness of the policy.

Objective:
To determine if:
1.    The mere announcement of the possibility of CL have an effect on medicines prices and sales volume of generic
      and branded medicines in the private and public market in Ecuador?
2.    The actual issuance of CLs have an effect on medicines prices and sales volume of generic and branded medicines
      in the private and public market in Ecuador?                                                                            65

Methods:
Datasources: Ministry of Health, international organizations’ website, press notes and publications and IMS sales data from
Ecuador and a small selection of other South American countries.

A time series analysis will be undertaken from 1 January 2007 until 26 October 2012. We will identify around 30 high-cost
and/ or high consumption medicines in Ecuador, some of these will be specifically licensed, some will not.

To control for independent changes in prices, we will track prices and volumes of a cohort of medicines of the same
therapeutic groups as the 30 “standard” medicines but that are unlikely to be affected by the announcement of compulsory
licensing.
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                                                                 Other abstracts – not to be presented


                                     Access to medicines used to treat chronic disease in low-
                                                                and middle-income countries

                                                                  Roubos1, Cameron A.,2, Ewen M.3, Laing R.O. 4.
                                                                            1. Utrecht University, The Netherlands
                               2. World Health Organization, Switzerland; and Utrecht University, The Netherlands
                                                                  3. Health Action International, The Netherlands
                                                                       4. World Health Organization, Switzerland




Rationale
Chronic, non-communicable diseases are the leading cause of death in low- and middle-income countries. Of all deaths
due to chronic diseases worldwide, approximately 80 per cent occur in low- and middle-income countries. Developing
countries undergoing an epidemiological transition from infectious and parasitic diseases to non-communicable diseases
require health systems modifications to address the long-term nature of these diseases. Providing equitable access to
essential medicines is a key component of a comprehensive health system response to the prevention and management
of chronic diseases. Limited studies have shown that low medicine availability can be a barrier to access to treatment for
these conditions, particularly in the public sector.

Objective
                                                                                                                               67
The research aims to review existing evidence on access to medicines used to treat chronic disease in low- and middle-
income countries, with a particular emphasis on medicine availability.

Methodology
A comprehensive literature review was conducted to find evidence on access to medicines used to treat chronic disease.
Searches were limited to developing countries, defined as countries with a World Bank country classification of low-,
lower-middle- or upper-middle-income economy. Peer-reviewed publications were identified with PubMed (MEDLINE)
using search terms related to access to essential medicines, chronic diseases and developing countries. The search was
conducted in English and included articles through October 31, 2009. A systematic search of grey literature (e.g., published
reports, technical documents, etc) was also performed which included an online search (e.g., Google) with the search terms
above, a search of websites of international organizations, and a review of the reference lists in published papers.
68
                                                                                 Utrecht   I WHO Winter Meeting 2010


                                                                  Other abstracts – not to be presentedo


                                                              Medicine selection – the Ghanaian experience

                                                                                     M. Gyansa-Lutterodt, A. Koduah
                                                                                   Ghana National Drug Program, Ghana

Rationale
The selection of the right medicine for a particular disease is the critical part of the development of the standard treatment
guidelines. Standard Treatment Guidelines (STG) are systematically developed statements that assist prescribers in
deciding on appropriate treatments for specific clinical problems. They usually reflect the consensus on the optimal
treatment options within a health system and aim at beneficially influencing prescribing behaviour at all levels of care.

Objectives:
1. To select cost effective treatment
2. Evidence based selection of medicines for disease condition

Method
Experts with practical knowledge in general medicine, surgery, clinical pharmacy, pharmacology, and pharmaceutical policy
are selected from leading healthcare facilities in the country. They are inaugurated by the minister of health. Conflict
of interest is disclosed if any. These experts through practice and evidence based information recommends specific
medications also stating their evidence rating levels.

                                                                                                                                 69
Experts were divided into specific groups for different disease conditions. The group’s finding are discussed by all experts
as this enable specific groups present their recommendations, as well as other stakeholders. The resulting document is
reviewed taking into account all recommendations and comments for other stakeholders. An editorial group constituted
out of the experts review the document, using a clear set out procedures. The document is then present at a forum for
inputs, comments, clarification and recommendations. These selected medicines are discussed with larger stakeholder
participation including the National Health Insurance Authority.

Results
Evidence based selected medicines for treatment guidelines.
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                                                                 Other abstracts – not to be presentedo


                                    Medicine expenditures in the Republic of Tatarstan: 2003-2008

                                      E.G. Aleksandrova, I.S. Burashnikova, A.V. Kuchaeva, L.E. Ziganshina
                                                                                 Kazan State Medical Academy, Russia




The Republic of Tatarstan has successfully implemented the formulary system as the key component of pharmaceutical
policy of the Ministry of Health and has introduced the ___/VEN analysis on regular basis.

The population of the Republic of Tatarstan is 3.7 million people (2009).

Medicine expenditures of the governmental healthcare institutions increased over the five year period: 2003 - 420 million
rubles, 2004 – 511; 2005 – 430; 2006 – 573; 2007 - 718; and 2008 - 1 billion and 84 million rubles.

The expenditures on the vital medicines increased over time: 50% - in 2003; 59% - in 2004; 64% - in 2005. Simultaneously
the expenditures on the non-essential medicines decreased: in 2003 - 14%, in 2004 - 8%, in 2005 - 7% of the medicine
budget, thus coming close to the recommended values: 70-80% of medicines budget for Vitals (V), 10-20% - for Essentials
(E), and 5-10 % - for Non-essentials (N).

However, the achieved results were not sustainable after 2005: the proportion of expenditures on vital medicines decreased
                                                                                                                              71
and on non-essentials - increased by 2008. This may be due to promotion of new expensive medicines. Special efforts are
needed to maintain VEN parameters at the recommended level.

Further improvement of formulary regulation at all levels of health system and educational intervention for health managers
and physicians are needed, as well as free access to independent, evidence-based medicine information.
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                                                                              Utrecht   I WHO Winter Meeting 2010


                                                                Other abstracts – not to be presentedo


                                                    Consumption of typical versus atypical neuroleptics
                                                           and expenditures at a psychiatric hospital

                                                              EI.S.Burashnikova, A.V.Kuchaeva, L.E.Ziganshina
                                                                                Kazan State Medical Academy, Russia




Since 2003 the ___/VEN and DDD analyses of medicine expenditures and consumption have been carried out on regular
basis at the Clinical Psychiatric Hospital. New atypical neuroleptics arrived on the Russian pharmaceutical market. We
compared consumption of typical and atypical neuroleptics and expenditures for the five year period (2003-2008).
The DDD methodology allowed us to compare neuroleptics’ consumption at various time intervals. Neuroleptic consumption
decreased over the studied period of time: from 133 to 105 DDD/100 bed-days. Haloperidol consumption decreased from
49 to 31 DDD/100 bed-days. Chlorpromazine consumption was between 18 and 19 DDD/100 bed-days. Overall consumption
of typical neuroleptics decreased over 5 years from 107 to 84 DDD/100 bed-days. Consumption of such atypicals as
quetiapine, olanzapine, risperidone, ziprasidone, sertindol and aripiprasole in 2008 varied between 0.2 to 4.0 DDD/100
bed-days. Totally atypicals’ consumption in 2008 was 21 DDD/100 bed-days.
Atypical neuroleptics’ expenditures increased by nearly 4 times: from 7,2 million rubles in 2003 to 27,3 million rubles in
2008. Typical neuroleptics’ expenditures increased by 2 times from 3 million rubles in 2003 to 6 million rubles in 2008.

Conclusion
                                                                                                                             73
Over the five year period (2003-2008) expenditures on atypical neuroleptics increased considerably, but only very few
patients benefited from these medicines. The increased atypicals’ expenditures did not meet the hospital needs in
neuroleptic therapy. Effective medicine policies and efficient procurement management are urgently needed.
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Utrecht   I WHO Winter Meeting 2010




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