Conflict of interest: journals, guidelines, and specialist

societies

Richard SmithEditor, BMJ

Rome October 2001

Rome (you) and Scotland (me)• The native Caledonians preserved in the Northern extremity

of the island their wild independence, for which they were not less indebted to their poverty than to their valour. Their incursions were frequently repelled and chastised, but their country was never subdued. The masters of the fairest and most wealthy climates of the globe turned with contempt from gloomy hills assailed by the winter tempest, from lakes concealed in blue mist, and from cold and lonely heaths over which the deer of the forest were chased by a troop of naked barbarians. Edward Gibbon

What I want to talk about

• What is conflict of interest?

• How common is it?

• Does it matter?

• Conflict of interest and journals

• Conflict of interest and guidelines

• Conflict of interest and societies

• How to respond?

What is conflict of interest?• Conflict of interest is a set of conditions in

which professional judgement concerning a primary interest (such as patients' welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain).

Thompson DF. Understanding financial conflicts of interest. N Engl J Med 1993; 329: 573-576

What is conflict of interest?

• Conflict of interest is a condition not a behaviour.

Do you have a conflict of interest?• 1. Have you in the past five years accepted the following from

an organisation that may in any way gain or lose financially from the results of your study or the conclusions of your review, editorial, or letter:

• ______ Reimbursement for attending a

symposium? • ______ A fee for speaking? • ______ A fee for organising education? • ______ Funds for research? • ______ Funds for a member of staff? • ______ Fees for consulting?

Do you have a conflict of interest?• 2. Have you in the past five years been employed by an

organisation that may in any way gain or lose financially from the results of your study or the conclusions of your review, editorial, or letter?

• 3. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially from the results of your study or the conclusions of your review, editorial, or letter?

• 4. Do you have any other competing financial interests? If so, please specify.

Competing interest statement

• Competing interests: RS has been reimbursed by Shangri La Products, the manufacturer of elysium, for attending several conferences; TD has been paid by Shangri La Products for running educational programmes and has her research registrar paid for by the company; JS has shares in the company.

Do you have a conflict of interest?• We are restricting ourselves to asking directly about competing

financial interests, but you might want to disclose another sort of competing interest that would embarrass you if it became generally known after publication. The following list gives some examples.

• (a) A close relationship with, or a strong antipathy to, a person whose interests may be affected by publication of your paper.

• (b) An academic link or rivalry with somebody whose interests may be affected by publication of your paper.

•

Competing interest statement• Competing interest: The BMJ hardly ever publishes animal

research. This is not because we are against animal research but rather because we favour research that may have results that are directly applicable for clinicians and those making public policy. While doing a degree in experimental pathology in 1973 I implanted stem cell leukaemias into rats. I wrote this editorial a few days after our pet rabbit was killed by a fox. Her death upset me much more than I ever expected.

• Statement for an editorial by Richard Smith, BMJ editor, to an editorial on animal research

How common are competing interests?

• 75 articles

• 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

Why don’t authors declare conflicts of interest?

• Some journals don’t require disclosure

• The culture is one of not disclosing

• Authors think that it’s somehow “naughty”

• Authors are confident that they are not affected by conflicts of interest

Does conflict of interest matter?• Financial benefit makes doctors more likely to refer

patients for tests, operations, or hospital admission, or to ask that drugs be stocked by a hospital pharmacy.

• Original papers published in journal supplements sponsored by pharmaceutical companies are inferior to those published in the parent journal.

• Reviews that acknowledge sponsorship by the pharmaceutical or tobacco industry are more likely to draw conclusions that are favourable to the industry.

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

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.

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)

Journals and conflict of interest• Conflict of interest is common among

authors

• Most journals have long had policies that conflicts of interest should be declared

• But mostly they are not

• Yet conflicts of interest seem to have a strong effect on results and how they are interpreted

How do conflict of interest statements affect readers’ perceptions of studies?

• 300 BMJ readers randomised to receive a study with a competing interest statement declaring a relationship with a pharmaceutical company or the same study with no competing interest statement

• 46% response rate

• Readers rated the study with the competing interest statement significantly lower on all of five characteristics: interest, importance, relevance, validity, and believability

Conflict of interest within journals• Drug company sponsored supplements have been

shown to be of inferior quality--but many journals publish them. They are a major source of income

• Some journals exist simply to publish studies funded by pharmaceutical companies

• Many journals depend heavily on advertising: does this influence their decisions on what to publish?

Conflict of interest within journals

• Some journals publish advertising next to related articles? Does this influence what they publish?

• Some journals make millions of dollars from reprints of articles--mostly of randomised trials funded by pharmaceutical companies

• With the big five journals around three quarters of trials are funded by pharmaceutical companies (30% for BMJ)

Conflict of interest within journals• Acceptance of a particular study may be

accompanied by a reprint order of more than a million dollars. It’s not difficult to tell which studies might produce such an order. Does this influence the decision on which studies to publish?

• Few (if any) journals publish the competing interests of their editors, editorial board, and management team and board

Conflict of interest within journals• Many specialist societies depend financially on their

journals• This probably influences decisions on how journals behave--

over supplements, advertising, pricing, and making material available for free

• Almost no specialist societies have allowed their journals to place their studies (often funded with public money) on Pubmed Central, but isn’t Pubmed Central good for science and medicine and aren’t the societies supposed to be about science and medicine?

Words on guidelines and specialist societies

• Most guidelines produced by specialist societies are of poor quality

• Of 431 guidelines produced by specialist societies only one in seven gave information on who produced them, only about a fifth did a search of evidence, and only a quarter graded recommendations

• Grilli R, Magrini N, Penna A, Mura G, Liberati A. Practice guidelines developed by specialty societies: the need for critical appraisal. Lancet 2000; 355: 103-6.

• In specialty guidelines for colon cancer screening radiologists recommend barium enemas while gastroenterologists recommend colonoscopy.

A cautionary tale 1

• Many trials suggest that thrombolytic therapy may be harmful in acute stroke

• Despite that the American Heart Association has recently recommended tPA as a Class I (“definitely recommended”) intervention for stroke in its Guidelines 2000.

A cautionary tale 2

• The AHA claims that it assembles ‘independent’ panels to make recommendations but will not release conflict of interest statements signed by panelists.

• Independent verification reveals that most of the AHA’s expert stroke panelists have had ties to the manufacturers of tPA

A cautionary tale 3

• Genentech, the US manufacturer of tPA, contributed over $11 million to the AHA in the decade prior to the AHA’s recommendation.

• Is this all a coincidence? Even if it is, it looks bad.

• A tale told to me by Jeanne Lenzer, medical investigative journalist

How to respond to conflict of interest?

• “Disclosure is almost a panacea.” John Bailar, professor of statistics, University of Chicago

• Disclosure by authors, reviewers, editors, editorial boards, management committees, presidents of societies

• “What isn’t transparent is assumed to be biased, incompetent, or corrupt.”

How to respond to conflict of interest?• “If in doubt, disclose.”• Sometimes the conflict will be so strong that it will forbid

participation• The danger of trying to eradicate conflict of interest is

that it may encourage deception• “The only person who doesn’t have a vested interest in a

subject is somebody who knows nothing about it”• “The only people who don’t have personality disorders

are those who don’t have personalities.”

Conclusions• Concern about conflict of interest is not

just political correctness

• Conflict of interest has an important impact on the information reaching health professionals and the public and on patient care

• Conflict of interest is very common in medicine

Conclusions

• Most conflicts of interest in medicine are not disclosed

• Yet disclosure should be the main response to conflict of interest

• We in health care need to do a better job of managing conflict of interest

• This talk is available on www.bmj.com