Conflict of interest: my journey

Richard SmithEditor, 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 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: 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?

• 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.

• 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• 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

• 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 ClarkPharmaceutical industry sponsorship and research outcome and quality: systematic reviewBMJ, 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

• But he held a patent on a transdermal lithium patch that the review mentioned favourably

• 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

• 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

• 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”