Transcript Conflict of interest: my journey

Conflict of interest:
my journey
Richard Smith
Editor, BMJ
www.bmj.com/talks
My journey
• 1985: “What is the problem?”
• 1990: It’s a form of political
correctness
• 1991: “Nevertheless, we’d better take it
seriously”
• 1994: “It’s hard to get people to take it
seriously”
• 1997: “We have to do better to get
authors to declare conflicts of interest”
My journey
• 1999: “This matters a lot. We must do better.”
• 2002: “Should we get people to declare
amounts of money in their conflicts of
interest?”
• 2003: “What about editors and their teams?”
• 2003: “Maybe journals are simply an part of
the marketing arm of pharmaceutical
companies and maybe doctors are their
agents”
• 2004 (?): “The circles of hell are filled with the
conflicted”
1985: “What is the problem?”
• Few doctors and researchers have
conflicts of interest
• Doctors and researchers are honest
• In properly done trials conflicts of
interest don’t matter because the
science is pure
• Good peer review solves the problem
1990: “It’s a form of political
correctness”
• Even if some doctors do have
conflicts of interest the problems
that arise as a result are trivial
• There are much more important
issues to worry about
• It’s necessary to be seen to be
concerned, but it’s not worth much
effort
1991: “Nevertheless, we’d
better take it seriously”
• Few doctors and researchers have
conflicts of interest
• Actually most do
• Some of the conflicts are very
substantial (tens of thousands of
dollars)
• Most are not declared
1991: “Nevertheless, we’d
better take it seriously”
• Doctors and researchers are honest
• Unfortunately some are not
• Honesty is not something you have
or don’t have: it’s on a spectrum and
is not a state but rather a
destination that is never reached
• “Everybody has their price”
• It’s a matter of bias not honesty. And
bias is unconscious and pervasive
1991: “Nevertheless, we’d
better take it seriously”
• In properly done trials conflicts of interest don’t
matter because the science is pure
• Conflict of interest affects the kinds of studies that
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are done
Drug treatments are much more studied than non-drug
treatments in hypertension, obesity, diabetes, etc
Conflict of interest means that “head to head” trials
are avoided
It is quite possible to design trials so that you are
highly likely to get the result you want and unlikely to
get one you don’t
Bias is unconscious and pervasive
1991: “Nevertheless, we’d
better take it seriously”
• Good peer review solves the problem
• No, it doesn’t
• Peer review is a lottery, highly
subjective, slow, expensive, biased,
ineffective, easily abused, and hopeless
for detecting fraud
• Nevertheless, it’s the least worst system
we have--but must be bolstered in every
way--for example, by getting authors to
declare conflicts of interest
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.”)
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: 101105
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?
• 11 studies compared the outcome of
studies sponsored by industry and those
not so sponsored
• In every study those that were sponsored
were more likely to have a finding
favourable to industry
• When the results were pooled the
sponsored studies were almost four times
more likely to find results favourable to
industry
•
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.
Does conflict of interest
matter?
• 106 reviews, with 37% concluding that passive
smoking was not harmful and the rest that it
was.
• Multiple regression analysis controlling for
article quality, peer review status, article topic,
and year of publication found that the only factor
associated with the review's conclusion was
whether the author was affiliated with the
tobacco industry.
• Only 23% of reviews disclosed the sources of
funding for research.
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Barnes DE, Bero LA. Why review articles on the health effects of passive
smoking reach different conclusions. JAMA 1998; 279: 1566-1570
Does conflict of interest matter?:
third generation contraceptive pills
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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.
Sponsored research
• A systematic review found 30 studies that compared
research funded by drug companies research funded by
other sources
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Company sponsored research more likely to be published
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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)
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None of the 13 studies that analysed methods reported
that studies funded by industry was of poorer quality
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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.
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
1994: “It’s hard to get
people to take it seriously”
• Most authors wouldn’t declare
conflicts of interest
• The culture was one of not
doing so
• They thought it was “naughty”
• The were confident they weren’t
influenced by their conflicts
1997: “We have to do better to get authors to
declare conflicts of interest”
• Ask authors to complete a specific
form
• Concentrate on financial conflicts
• Change the name from conflicts of
interest to competing interests
• Require authors to say something
• Embarrass those who say they don’t
have a competing interest but do
1999: “This matters a lot. We
must do better.”
• The harder I look at the
evidence on the effects of
conflict of interest the more it
convinces me
• A ghastly story
Nature Neuroscience and
conflict of interest
•
Charles Nemeroff,professor of neuropsychopharmacology at
Emory University School of Medicine, Atlanta, published a
review on mood disorders in the February issue of Nature
Neurosciences
•
Declared no conflicts of interest
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But he held a patent on a transdermal lithium patch that the
review mentioned favourably
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Member of the scientific advisory board of Corcept
Therapeutics—a company carrying out trials with
mifepristone, which was mentioned favourably in the
review—and, as such, was given an option to purchase 72
000 shares at a total cost of $21.60
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Director and chairman of the psychopharmacology advisory
board of Cypress Bioscience, which has only one product—
milnacipran—which was mentioned in the review
2002: “Should we get people to
declare amounts of money in
their conflicts of interest?”
• Well, should we?
• Nobody does
• But is there a difference
between being bought lunch and
doing one day’s work a year for
$20 000?
2003: “What about editors and
their teams?”
• Editors, their teams, and their
boards are worse than anybody
• They virtually never declare
conflicts of interest
2003: “Maybe journals are simply an part of
the marketing arm of pharmaceutical
companies and maybe doctors are their
agents”
• “Unfortunately we’re seen as an
extension of the industry’s
marketing arms.”
• Richard Smith, The Times,
Saturday 25 October 2003
Does conflict
of interest
lead you to
hell?
Conflict of interest and
the circles of hell
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Avaricious and prodigal
Gluttonous
Wrathful and gloomy
Heretics
Assassins, tyrants, warmongers
Suicides
Frauds and the malicious
– Seducers and pimps
– Hypocrites
– Simonists
– Barraters, those who bartered public office for private gain
– Magicians, diviners, seducers, fortune tellers, and
panderers—“a particularly frolicsome band of demons”