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Is the relationship between the industry and prescribers _doctors by lifemate

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									 Is the relationship
between the industry
  and prescribers
(doctors) in trouble?
       Richard Smith
        Editor, BMJ
     www.bmj.com/talks
      Answer
•It could certainly
 be improved--
 made more
 ―professional‖
    What I want to talk about
•   A story of trouble
•   The context of the relationship
•   How is the world changing?
•   Another story of trouble
•   What are the current relationships between doctors
    and industry?
•   Conflicts of interest: a case study of entanglement
•   How might the relationships between doctors and
    industry be improved?
•   Another story of trouble
•   Conclusions
          A story of trouble I
• AstraZeneca’s tactics in promoting
  rosuvastatin "raise disturbing questions about
  how drugs enter clinical practice and what
  measures exist to protect patients from
  inadequately investigated medicines"
• The Galaxy series of clinical trials, which
  investigated the efficacy of rosuvastatin,
  included "weak data," "adventurous statistics,"
  and "marketing dressed up as research,"
• It has been an "unprincipled campaign"
• Richard Horton, editor, Lancet

•   Lancet 2003;362: 1341
     A story of trouble I
• Regulators, doctors, and patients as
  well as AstraZeneca have been
  poorly served by your flawed and
  incorrect editorial. I deplore the fact
  that a respected scientific journal
  such as The Lancet should make
  such an outrageous critique of a
  serious, well studied, and important
  medicine
• Tom McKillop, CEO, AstraZeneca
          The context
• Virtually all new drugs in the past 50
  years have been discovered or
  manufactured by the drug industry
• The industry has consistently been
  one of the most profitable industries
  and is truly global
• It has great political power,
  particularly in the United States
          The context
• Medicine is also global, but there is
  no international ―health
  organisation‖ (WHO, WMA) that has
  the resources and power of the
  industry
• Research-based companies are
  merging--driven in large part by the
  costs of discovering new drugs and
  bringing the to market
        The context
• The power of generic
  companies (many in India and
  Brazil) is rising
• The cost of bringing a drug to
  market is huge and rising--
  which may be no bad thing for
  large companies as it raises
  ―the barrier to entry‖
           The context
• The industry has been largely cut off from
  the people who take their products
• The industry has concentrated its
  enormous marketing resources on doctors-
  -because they have written the
  prescriptions
• The ―spend‖ per doctor is enormous
• Doctors have become addicted to the
  largesse
           The context
• Companies must produce a good
  return on investment for shareholders
• They ideally do this through producing
  much needed new drugs--from which
  everybody benefits
• But their legitimate commercial
  values sometimes (even often)
  conflict with the values of health care
  workers and systems
 The context: examples of
      value clashes
• It cannot make commercial sense to
  produce new drugs for very rare
  conditions or conditions affecting
  those who have no money to pay
• It does make sense to produce a ―me
  too‖ drug for a profitable market and
  market it as hard as possible
• Restrictions on marketing efforts are
  legitimately strained against
 The context: examples of
      value clashes
• Drug treatments are favoured over non-
  drug treatments
• Companies are understandably reluctant
  to fund large head to head trials
• Companies are clever enough to
  ―honestly‖ get the results from trials they
  fund
• Companies favour secrecy for
  commercial reasons; doctors and
  patients want transparency
  The world is changing
• Drug companies have a productivity
  crisis--companies were producing 3
  new chemical entities each year on
  average; now it’s 0.3 (Dresdner
  Kleinwort Wasserstein)
• In these circumstances companies
  may need to market still harder the
  products they have and ―invent‖ new
  diseases
  The world is changing
• The current business model of research-
  based companies is unsustainable--
  Dresdner Kleinwort Wasserstein
  – New discoveries are down
  – 12-15% increase in sales (half of it coming from
    price increases) is becoming impossible to
    sustain because of political pressure (4th
    hurdles, NICE, etc)
• Answer: more mergers, creating
  ―monopolies‖ in particular therapeutic
  areas
  The world is changing
• Direct to consumer advertising has arrived
  in the US and New Zealand and will
  probably be unstoppable across the world
• Companies have to increase their
  marketing spend dramatically
• New ―relationships‖ are created with
  consumers
• Doctors generally resent companies ―going
  over their heads‖ and creating
  expectations that doctors must meet
  The world is changing
• Increasing numbers of bodies—for
  example, NICE and HMOs—are
  interested in controlling prescribing
• A WHO report praises NICE but
  criticises it for being too close to
  industry
• Other prescribers are appearing
• Doctors may not be the target they
  once were
  The world is changing
• There is growing understanding of
  how the industry can get the results
  it wants—three papers for the
  Christmas BMJ
• Governments are increasingly
  interested in public funding of trials
• ALLHAT and the Women’s Health
  Initiative have given that interest a
  boost
             Trouble 2
• A journal publishes a paper that combines
  two trials A and B that show that a drug
  manufactured by Y, the sponsors of the
  studies, is better than a drug manufactured
  by Z
• A correspondent points out that trial A has
  already been published—a case of
  duplicate publication?
• Trial A and the paper (A and B) had only
  one common author—an employee of Y
             Trouble 2
• It also emerges that trial B did not find
  that Y had better outcomes than Z
• Then it emerges that on the FDA
  website the trials A and B both included
  other outcome measures—possibly
  ones that matter more to patients—
  where Z had better outcomes than Y
• How should the editors/publishers
  respond?
  What are the
     current
  relationships
between doctors
 and industry?
  16 forms of entanglement between
     doctors and drug companies

• Face to face visits from drug
  company representatives
• Acceptance of direct gifts of
  equipment, travel, or
  accommodation (―Will you advertise
 my drug on your person for a year if I
 pay you 20p?‖)
• Acceptance of indirect gifts, through
  sponsorship of software or travel
  16 forms of entanglement between
     doctors and drug companies

• Attendance at sponsored dinners and
  social or recreational events (―If they have
  to pay the full whack they won’t come?‖)
• Attendance at sponsored educational
  events, continuing medical education,
  workshops, or seminars (―Could you hurry
  up so we can get to the vol au vents?‖)
• Attendance at sponsored scientific
  conferences (―Bugger Bognor, but the
  Gritti Palace in Venice sounds good.‖)
  16 forms of entanglement between
     doctors and drug companies

• Ownership of stock or equity holdings
• Conducting sponsored research (―It’s so
  hard to get money from the MRC and £800
  for registering a patient is not bad.‖)
• Company funding for medical schools,
  academic chairs, or lecture halls
• Membership of sponsored professional
  societies and associations
• Advising a sponsored disease foundation
  or patients' group
  16 forms of entanglement between
     doctors and drug companies

• Involvement with or use of sponsored
  clinical guidelines
• Undertaking paid consultancy work for
  companies (―A return flight on Concorde,
  five nights at the Ritz Carlton, and 20
  grand is not bad for two hours of blah.‖)
• Membership of company advisory boards of
  "thought leaders" or "speakers' bureaux‖
  (―Flattery and money: I can resist
  everything except temptation.‖)
    16 forms of entanglement between
       doctors and drug companies

•    Authoring "ghostwritten" scientific
    articles (A critic on Naomi Campbell’s
    autobiography: ―If she can’t be bothered to
    write it I can’t be bothered to read it.‖)
• Medical journals' reliance on drug
  company advertising, company purchased
  reprints, and sponsored supplements (―It’s
    a million quid and £800 000 profit for
    reprints of a major trial. Without it I might
    have to lay off staff. But we’re not
    influenced in our decision making.‖)
  Does all this matter?
• Virtually all new drugs, which
  have been so important for
  medicine, have come from drug
  companies
• Drug companies must have the
  right to market their products
• Prescribing is influenced--often
  to be unnecessarily expensive
  Does all this matter?
• Information is biased
• Doctors are too dependent on
  drug companies for both
  education and information
• Companies spend more on
  marketing than on research
• Costs are inflated
Conflicts of interest: a
    case study in
    entanglement
      How common are competing
             interests?
• A quarter of US researchers have received
  pharmaceutical funding
• Half have received ―research related gifts‖
• An analysis of 789 articles from major
  medical journals found that a third of the
  lead authors had financial interests in their
  research—patents, shares, or payments for
  being on advisory boards or working as a
  director
•   Bekelman JE, Li Y, Gross CP. Scope and impact of financial
    conflicts of interest in biomedical research. A systematic
    review. JAMA 2003; 289: 454-65.
      How common are competing
             interests?
• 75 pieces giving views on calcium channel
  blockers
• 89 authors
• 69 (80%) responded
• 45 (63%) had financial conflicts of interest
• Only 2 of 70 articles disclosed the
  conflicts of interest
•   Stelfox HT, Chua G, O'Rourke K, Detsky AS. Conflict of interest in the
    debate over calcium channel antagonists. N Engl J Med 1998; 338: 101-
    105
       Do authors declare
      conflicts of interest?
• 3642 articles in the five leading
  general medical journals (Annals
    of Internal Medicine, BMJ, Lancet,
    JAMA, and the New England
    Journal of Medicine)
• Only 52 (1.4%) declared authors'
  conflicts of interest
•   Hussain A, Smith R. Declaring financial competing interests:
    survey of five general medical journals. BMJ 2001;323:263-4.
    Does conflict of interest
           matter?
• Is there a relationship between
  whether authors are supportive
  of the use of calcium channel
  antagonists and whether they
  have a financial relationship
  with the manufacturers of the
  drugs?
•   Stelfox HT, Chua G, O'Rourke K, Detsky AS. Conflict of interest in the
    debate over calcium channel antagonists. N Engl J Med 1998; 338: 101-
    105
         Sponsored research
•   A systematic review found 30 studies that compared
    research funded by drug companies research funded by
    other sources
•   Company sponsored research more likely to be published
•   Studies sponsored by pharmaceutical companies were
    more likely to have outcomes favouring the sponsor than
    were studies with other sponsors (odds ratio 4.05; 95%
    confidence interval 2.98 to 5.51; 18 comparisons)
•   None of the 13 studies that analysed methods reported
    that studies funded by industry was of poorer quality
•   Joel Lexchin, Lisa A Bero, Benjamin Djulbegovic, and Otavio Clark
    Pharmaceutical industry sponsorship and research outcome and quality: systematic review
    BMJ, May 2003; 326: 1167 - 1170.
     Does conflict of interest matter?:
    third generation contraceptive pills
•    At the end of 1998 three major studies without sponsoring from
     the industry found a higher risk of venous thrombosis for third
     generation contraceptives; three sponsored studies did not.
•    To date, of nine studies without sponsoring, one study found no
     difference and the other eight found relative risks from 1.5 to 4.0
     (summary relative risk 2.4); four sponsored studies found
     relative risks between 0.8 and 1.5 (summary relative risk 1.1)
•    The sponsored study with a relative risk of 1.5 has been
     reanalysed several times, yielding lower relative risks; after this
     failed to convince, a new reanalysis was sponsored by another
     company.
•    One sponsored study finding an increased risk has not been
     published.
•    Vandenbroucke JP, Helmerhorst FM, Frits R Rosendaal FR. Competing
     interests and controversy about third generation oral contraceptives. BMJ
     2000; 320: 381.
 What proportion of trials in the
 five major general journals are
       funded by industry?
•75% in Annals of
 Internal Medicine,
 Lancet, JAMA, and
 NEJM
•30%in BMJ
   In search of a
 better relationship
  between doctors
and drug companies
Proposals for disentangling
• Poll on bmj.com; 1479
  responding
• Would you like doctors to stop
  seeing drug company
  representatives, replacing them
  with more independent sources
  of health information?
• 79% yes
Proposals for disentangling
• Would you like doctors to stop
  receiving all forms of direct and
  indirect gifts from drug companies?
• Yes 84%
• Would you like industry-funded
  education of doctors replaced by
  education funded by more
  independent sources?
• Yes 84%
Proposals for disentangling
• Would you like doctors' professional
  associations and their peer-reviewed
  journals to reduce their reliance on
  industry funding to specified maximum
  levels?
• Yes 85%
• Would you like all financial relationships
  between doctors and drug companies
  conducted with transparent contracts that
  are disclosed to patients and the public?
• Yes 96%
Proposals for disentangling
• Would you like mechanisms that genuinely
  create more distance and independence
  between doctor/researchers and their research
  sponsors?
• Yes 83%
• Would you like government/public agency
  advisory panels, which are responsible for
  independent assessment of medical products
  or health policies, to reduce their reliance on
  doctors with financial ties to drug companies?
• Yes 87%
Proposals for disentangling

• Would you like to see these
  sorts of changes become
  the basis of a charter for a
  new relationship between
  doctors and drug
  companies?
• Yes 90%
Trouble 3—the
 sad story of
    HRT
   The sad tale of HRT
• Hormone replacement therapy for
  postmenopausal women was widely
  expected to reduce osteoporotic
  fractures, deaths from heart disease
  and stroke, and dementia

• A great many observational studies
  supported these expectations
         The sad tale of HRT
• An early analysis in the BMJ in 1997 of
  data from trials suggested that far from
  from decreasing deaths from
  cardiovascular events HRT might increase
  them
• Insults heaped on the authors and on the
  BMJ for publishing such ―rubbish‖
• Many of these comments came from
  authors with undeclared competing
  interests
•   Elina Hemminki and Klim McPherson
    Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from
    clinical trials
    BMJ, Jul 1997; 315: 149 - 153.
   Results of Women’s
    Health Initiative
• Began to be published in 2002
• Doubled deaths from breast cancer
• No decrease (and possibly an
  increase) in deaths from heart
  disease
• Increased thromboembolic disease
  and strokes
• Increase in dementia
• No improvement in quality of life
    The sad tale of HRT
• More than 100 million women worldwide
  have taken HRT
• Professor Bruno Müller-Oerlinghausen, the
  head of the German Commission on Safety
  of Medicines, called HRT a "national and
  international tragedy."
• Comparing it to thalidomide, he said that
  the "naive and careless use of a
  medication that is perceived as natural and
  optimal" had caused many unnecessary
  deaths among women.
    The sad tale of HRT
• In the 1960s American physician
  Robert Wilson wrote the influential
  Forever Feminine, extolling the
  virtues of HRT as a virtual fountain
  of youth for the "dull and
  unattractive" ageing woman
• In 2002 it emerged that Wyeth paid
  Wilson for the book
   The sad tale of HRT
• In 2002 the New York based Society
  for Women's Health Research, whose
  "sole mission is to improve the
  health of women through research,"
  held a celebrity gala celebrating
  women's "coming of age"
• The gala was entirely underwritten
  by Wyeth
• A few days later Wyeth donated £250
  000 to the society
     The sad tale of HRT
• Wyeth’s share price halved when the first
  results of the Women’s Health Initiative was
  published
• Phyllis Greenberger, CEO of the Society of
  Women’s Health Research, and her staff went
  on national radio and television talk shows
  attacking the findings of the WHI study and its
  authors
• "Instead of taking the side of its constituents
  the society seemingly took the side of its
  donors—and of Wyeth in particular."
    The sad tale of HRT
• Novo Nordisk hired German PR firm Haas
  & Health Partner which sent doctors
  letters downplaying the WHI results
• The letters emphasised that the
  "absolute risk for women is quite
  minimal" and were signed by Dr Irene
  Haas (a historian, according to her
  company's website)
• Doctors in Britain have been deluged
  with similar material
        Conclusions
• The drug industry does vital
  work
• Doctors and drug companies
  have become too entangled
• Some disentanglement would
  be good for everybody—
  patients, governments, doctors,
  and the industry

								
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