Conflicts of interest: a case study in entanglement

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Conflicts of interest a case study in
entanglement
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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
  researchpatents, 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.

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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

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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 2001323263-4.

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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

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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

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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.

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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

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In search of a better relationship between
doctors and drug companies
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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

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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

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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
•  

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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

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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

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Trouble 3the sad story of HRT
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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

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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 McPhersonImpact of
  postmenopausal hormone therapy on cardiovascular
  events and cancer pooled data from clinical
  trialsBMJ, Jul 1997 315 149 - 153.

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Results of Womens 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

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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.

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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

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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

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The sad tale of HRT

• Wyeths share price halved when the first results
  of the Womens Health Initiative was published
• Phyllis Greenberger, CEO of the Society of
  Womens 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
  donorsand of Wyeth in particular."

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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

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Conclusions

• The drug industry does vital work
• Doctors and drug companies have become too
  entangled
• Some disentanglement would be good for
  everybodypatients, governments, doctors, and the
  industry