Conflict of interest: an editor’s jaundiced view

1. Conflict of interest: an editor’s jaundiced view Richard Smith Editor, BMJ March 2003 www.bmj.com/talks

2. What I want to talk about • What is conflict of interest? • How common is it? • Does it matter? • How are readers affected by conflict of interest statements • Conflict of interest and journals • How to respond?

3. 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

4. What is conflict of interest? • Conflict of interest is a condition not a behaviour.

5. 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?

6. 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.

7. 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.

8. 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.

9. Do you have a conflict of interest? • (b) An academic link or rivalry with somebody whose interests may be affected by publication of your paper. • (c) Membership of a political party or special interest group whose interests may be affected by publication of your paper. • (d) A deep personal or religious conviction that may have affected what you wrote and that readers should be aware of when reading your paper.

10. 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

11. Conflicts of interest of editors • Nearly 20 years after asking authors to declare conflicts of interest we’ve declared those of editors • Editorial board • Executive team • BMJ Publishing Group board

12. Two questions • 1. Should we ask people to declare the relevant amounts in financial conflicts of interest? • Could there be a difference between being given a ham sandwich and flown to New York on Concorde and put up at the Plaza? • 2 Should we require people to declare non-financial conflicts of interest?

13. 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.

14. 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

15. 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.

16. Do authors declare conflicts of interest? • The journals now have a policy of requiring authors of randomised trials funded by industry to declare • The role of the sponsor in the study • Who controlled the decision on publication. • A study of trials in the same five journals showed that only the Annals of Internal Medicine had ever published such a statement

17. 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

18. 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 • Rochon PA, Gurwitz JH, Cheung M, Hayes JA, Chalmers TC. Evaluating the quality of articles published in journal supplements compared with the quality of those published in the parent journal. JAMA 1994; 272: 108-13.

19. 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.

20. 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

22. 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

23. 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.

24. 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

25. How do conflict of interest statements affect readers? • 300 BMJ readers randomised to receive a study on impact of pain from herpes zoster on patients’ daily functioning with • One group received the study with a competing interest statement declaring that they were employees of the company and owned shares • One group the same study with no competing interest statement • Asked to rate study for interest, importance, relevance, validity, and believability

26. How do conflict of interest statements affect readers? • 52% response rate • Readers rated the study with the competing interest statement significantly lower on all of five characteristics: interest, importance, relevance, validity, and believability • Chaudhry S, Schroter S, Smith R, Morris J. Does declaration of competing interests affect reader perceptions? A randomised trial. BMJ 2002; 325: 1391-2.

27. How do conflict of interest statements affect readers? • A further 150 readers sent the short report with a statement that one of the authors was a recipient of funding for studentships and research grants from the company • No difference from the group sent the paper with no competing interest

28. How do conflict of interest statements affect readers? • Paper on the use of problem lists in letters between hospital doctors and general practitioners • 150 no competing interest declared • 150 a statement that one of the authors was an employee of the company making the software and potentially owned stock/ or holds stock options within the company • 150 a statement that one of the authors is a recipient of funding for studentships and research grants from a company making medical management software

29. How do conflict of interest statements affect readers? • 66% response rate • No differences between groups • Schroter S, Chaudhry S, Smith R, Morris J, Barratt H

30. 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?

31. 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)

32. 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 journals publish the competing interests of their editors, editorial board, and management team and board

33. 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?

34. 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.”

35. 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.”

36. 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

37. Conclusions • Conflicts of interest statement seem to have an influence on readers’s perceptions of studies • 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