Beyond conflict of interestA common problemBuilding a convincing caseWhat should the BMJ be doing?

Beyond conflict of interest

Dear Editor,

We welcome the BMJ’s theme issue on conflicts of interest in scientific writing and research . The ethical challenge represented by the covert influence of the tobacco industry on academic research and publication needs a concerted response by all biomedical journals.

Tobacco industry papers published on the Internet by Action on Smoking and Health 1 expose how the tobacco industry has tried to influence research into tobacco and health. For example, Philip Morris fostered controversy about the effects of passive smoking on health, and countered authoritative reviews articles, by establishing an international network of paid scientific ‘consultants’. Their activities included: writing critical letters; publishing ‘review’ articles; establishing a ‘learned society’ on indoor air quality; and performing research into other causes of lung cancer (such as keeping pet birds) . The success of the strategy is demonstrated by Barnes and Bero’s study reported in Richard Smith’s editorial. Internal industry documents also describe how the US Tobacco Institute paid $2500 to $10,000 to authors of letters criticising the 1993 Environmental Protection Agency report which declared environmental tobacco smoke carcinogenic 2. Some letters were revised by law firms prior to publication.

Letters to scientific journals should be rigorous and unbiased 3 and not advocacy for sectional interests. Editors have a special responsibility to guard against bias in the correspondence column, especially when letters are not peer reviewed. The International Epidemiology Group recently circulated a code of practice for epidemiologists. This states that researchers should declare all actual, apparent or potential conflicts of interest to Ethical Review Committees, acknowledge publicly all sponsorship of research, and that epidemiologists should judge their work and that of colleagues impartially. 4 This code is in accord with Richard Smith’s recommendations.

Medical editors and eminent medical scientists should agree a code of practice for medical and epidemiology journals. Actions could include: keeping a register of scientists with tobacco-related interests; asking authors on tobacco-related papers (including letters) to declare conflicts of interest; checking authors credentials using the register of interests; and vigorous ‘naming and shaming’ of those exposed as covertly funded by the tobacco industry.

Chris Proctor of British American Tobacco argues that we should trust in the integrity of scientific researchers and the peer review process to guard against results from tobacco industry funded research being presented in a skewed manner or so as to confuse the public health message 5. The internal industry documents show that the right to such trust has long since been abrogated. The credibility of science as a whole, and medical and epidemiological research in particular, is too important to allow the tobacco industry’s efforts to go unchallenged.

Richard Edward, MFPHM Lecturer in Public Health Medicine
Raj Bhopal, MD Professor of Epidemiology and Public Health

Institution and address for correspondence:
Department of Epidemiology and Public Health
School of Health Sciences
The Medical School
University of Newcastle upon Tyne
NE2 4HH
P.R.Edwards@ncl.ac.uk

References
1. Action on Smoking and Health UK. Philip Morris Scandal documents show how Philip Morris and its lawyers, Covington and Burling invented and orchestrated controversy around passive smoking by infiltrating highly respected science and policy institution and by buying up scientists. Available from: URL: http://www.ash.org.uk/
2. Wadman M. Dilemmas for journals over tobacco cash. Nature 1998; 394: 609.
3. Bhopal RS, Tonks A. The role of letters in reviewing research. British Medical Journal 1994; 308: 1582-1583.
4. The IEA European Epidemiology Group. Good epidemiology practice. Proper conduct in epidemiological research. IEA European Epidemiology Group, 1998.
5. Proctor CJ. Tobacco research: collaboration, not confrontation, is the best approach. BMJ 1998; 317: 333-334.

Source of funding:
None

Conflict of interest:
Richard Edwards is (unpaid) Chair of Northern Action on Smoking and Health
Raj Bhopal is a non-executive director of the Health Education Authority

EDITOR - BMJ editor Richard Smith expresses concern about the influence of conflict of interest on publications1. Our recent finding within a Cochrane review2 supports the concern that drug company involvement in clinical trials affects outcome. The searches undertaken for the systematic review of clozapine vs. 'typical' antipsychotic drugs for those with schizophrenia identified 29 different randomised studies involving 2490 participants. Sixteen of the trials reported some kind of connection with the manufacturer of the compound. These studies were assumed to be 'sponsored studies'. Peto odds ratios (OR) and 95% confidence intervals (CI) were calculated for the primary outcomes of relapse, clinical improvement, and leaving the study early. The odds of relapsing were statistically significantly in favour of clozapine, in comparison to the older generation antipsychotics in the sponsored trials (OR 0.5 CI 0.3-0.7, 13 trials, 980 people). Non-sponsored studies reported statistically equivocal findings (OR 0.4 CI 0.1-1.4, 10 trials, 783 people). Both sponsored and non-sponsored studies suggested that clozapine mediates a clinically important improvement in those with schizophrenia when compared to the older drugs but again the former were more positive than trials not clearly supported by industry (random effects OR 0.4 CI 0.2-0.7, 9 trials, 1126 people; random effects OR 0.3 CI 0.1-0.7, 8 trials, 743 people, respectively). Sponsored studies also reported that significantly less people taking clozapine left the study early when compared to drugs such as chlorpromazine and haloperidol (OR 0.5 CI 0.4-0.7, 14 trials, 1245 people). Non-sponsored trials (12 trials, 950 people) did not show this degree of effect (OR 0.6 CI 0.3-1.2).

The observation that drug industry sponsorship causes more favourable outcomes is of concern. Our finding underpins how important transparency regarding drug company sponsorship is in assessing trial outcomes. Those undertaking drug treatment meta-analyses should investigate for significant sponsorship-bias by use of sensitivity analysis. It is also of concern that licensing authority decisions are mainly based on trials performed by industry and therefore do not have information from independent researchers. Of course the problem of conflicts of interest may be even greater outside of industry where trialists can have very considerable investment in their own particular brand of community care package or psychological intervention.

Kristian Wahlbeck, Editor
Cochrane Schizophrenia Group, Department of Psychiatry, University of Helsinki, PB 320, FIN-00029 HUCH, Finland

Clive Adams, Co-ordinator
Cochrane Schizophrenia Group, Summertown Pavilion, Oxford OX2 7LG

1. Smith R. Beyond conflict of interest. Transparency is the key. BMJ 1998;317:291-2. (1 August.)

2. Wahlbeck K, Cheine M, Essali MA. Clozapine vs. 'typical' neuroleptic medication for schizophrenia (accepted). In: The Cochrane Library, Issue 4, 1998. Oxford: Update Software.

8/12/98

BMJ has now joined several prominent medical journals that have recently clarified or revised their conflict of interest policies (1) ). Hopefully, BMJ will fare better than its counterparts in even-handedly enforcing its revised policy. In one well publicized case, a single day's consulting to an FDA panel was considered such a profound violation that the New England Journal of Medicine (NEJM) changed its conflict of interest rules.(2) However, in the case of an NEJM editorial which flatly dismissed the carcinogenic potential of environmental estrogens, long-term funding to the editorialist from the chemical industry went undisclosed, and when revealed was addressed by the editor's comment that "the line has to be drawn somewhere." (3) The executive editor of NEJM has also written a Wall Street Journal editorial suggesting that receiving grants from the National Institutes of Health can be a serious conflict of interest. (4) Such lack of consistency is a continuing source of frustration among scientists.

None of the recent clarifications/revisions have adequately addressed a new and alarming conflict of interest issue: the practice of paying scientists to write letters to the editor or editorials which present medicolegal positions of industry. Documents uncovered during tobacco litigation reveal that this practice has become widespread. Similarly, a recent front page article in the New York Times revealed a $5,000,000 (~£3,000,000) plan to recruit previously "neutral" scientists to create doubt about global warming. (5) Such initiatives corrupt the scientific literature and require aggressive measures by scientists and editors. A ”neutral” scientist might escape your attention. Thus, your plan to send authors of letters “a questionnaire to complete only if we suspect that authors might have competing interests” appears inadequate.

An important omission from your revised policy involves editors themselves. The executive editor of NEJM often appears at legal or media events sponsored by organizations representing the legal interests of the medical device industry. The editor of another journal devoted to womens' health serves prominently on the board of directors of a international medical device manufacturer. When these editors write editorials, review papers, or speak to the press do they represent the interests of their journals or their “competing interests?” An easy solution is available: editors of medical journals should publish their own conflicts of interests (including speaking, consulting and medicolegal activities) on a regular basis. Will BMJ editors lead on this issue, serving as an example to both its authors and other editors?

(400 words)

Robert F. Garry, Ph.D.
Professor
Department of Microbiology and Immunology
Tulane University School of Medicine
1430 Tulane Avenue
New Orleans, LA 70112
504-587-2027
504-588-5144 (FAX)
rgarry@tmcpop.tmc.tulane.edu

1. Smith R. Beyond conflict of interest: Transparency is the key. BMJ 1998;317:291-292.

2. Angell M, Kassirer JP. Editorials and conflicts of interest. N Engl J Med 1996; 335: 1055-1056.

3. Tye L. Journal fuels conflict of interest debate. Boston Globe, January 6, 1998. p.A1.

4. Angell, M. Tuskegee revisited. Wall Street Journal, October 28, 1997, p A18.

5. Cushman JH Jr. Industrial group plans to fight climate treaty. New York Times, April 26, 1998. p.A1.

Dr. Garry's conflicts of interests have been much discussed (please see:Tenenbaum et al., Lancet 1997;349, 1172-1173, and discussions in: Horton R. ibid, p 1112-1113; Marshall E. Science 1997; 276, 524; Kolata G. New York Times, July 15, 1998, pA12.[published erratum appears July 17, 1998, p A2])