Is the relationship between the industry and prescribers _doctors by lifemate


									 Is the relationship
between the industry
  and prescribers
(doctors) in trouble?
       Richard Smith
        Editor, BMJ
•It could certainly
 be improved--
 made more
    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
• 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
• 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
• The ―spend‖ per doctor is enormous
• Doctors have become addicted to the
           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
• 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
  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
  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
• 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
• 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
             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
  What are the
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
• 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
      How common are competing
• 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
•   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
• 75 pieces giving views on calcium channel
• 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-
       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
• 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
•   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-
         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
•    One sponsored study finding an increased risk has not been
•    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
•30%in BMJ
   In search of a
 better relationship
  between doctors
and drug companies
Proposals for disentangling
• Poll on; 1479
• 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
• 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
• 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
• Yes 90%
Trouble 3—the
 sad story of
   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
• Insults heaped on the authors and on the
  BMJ for publishing such ―rubbish‖
• Many of these comments came from
  authors with undeclared competing
•   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
• 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
• 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
• "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
• The drug industry does vital
• 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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