Conflict of interest in biomedical publications

The conflict of interest in company-sponsored trials is a major concern for all those who are involved in biomedical publication. The policy of disclosure of conflict of interest and financial assistance has been adopted by the Indian Journal of Ophthalmology (IJO).¹ The readers of the journal should be aware that conflict of interest may involve the authors, institution, industry, reviewers, and editorial board including the editor. The purpose of this editorial is to familiarize the readers with the possible effect of conflict of interest at various levels. The journal editors take various measures to limit this effect to the bare minimum.

The issue of faulty designs in company-sponsored trials has been discussed in the previous editorial.¹ Another area of manipulation is the presentation of data and its analyses. Usually the full data is not made available to the participating researchers in company-sponsored trials. The authors should insist on free access to full data. Authors should be free to perform statistical analyses of the data independently and to publish the data as they consider fit. The freedom of publication and presentation of results should rest with the researcher, rather than the sponsors. Multiple publication, selective publication and selective reporting are established irregularities in publications involving company-sponsored trial.² These measures can tilt the outcome in favor of certain products erroneously.

Sponsors are known to obstruct the publication of reports with negative findings.³ This attitude is not correct and amounts to betraying public trust. Non-publication of negative outcome, selective publication, multiple publication and selective reporting tend to skew the evidence. The meta-analysis by Blumenthal et al. reported that 19.8% of academic life scientists from major institutions had delayed publication for more than six months at the insistence of the sponsors.⁴ Boots was successful in delaying the publication of one study for almost seven years wherein the sponsor′s synthetic thyroid, synthyroid was found to be equally effective as compared to three other competitive products whereas the sponsor had expected synthyroid to be proved superior.^5,6 In another trial the company terminated the study prematurely due to safety concerns and the researcher was threatened with legal consequences if he/she disclosed the concerns to any third party without the consent of the sponsor.⁷

The IJO is going to adopt a policy wherein the principal author should declare in writing that he/she is in possession of full data and has the right to publish the research independent of the sponsors. Without receiving such assurance from the main author, the article may not be sent for review at all. Ideally, the companies are expected to take four steps in dissemination in case of a trial with adverse impact on patients.⁸

i. Initiate timely and complete updates of the package inserts.

ii. Concurrently contact healthcare providers with direct written communications.

iii. Simultaneously reinforce research messages verbally to individual clinicians and

iv. Employ mass media approach to reach patients.

The National Heart, Lung and Blood Institute (NHLBI) initiated the Antihypertensive and Lipid Lowering to prevent Heart Attack Trial (ALLHAT) to study the superiority of newer and more costly agents against the inexpensive low-dose generic diuretics in 1994. The superiority of diuretics over the alpha blocker (doxazosin) was proved so convincingly that the study had to be terminated prematurely and the doxazosin treatment arm was advised to switch to other medication. The findings were published in literature.⁹ However, the manufacturer of doxazosin (Pfizer) did not take any of the four steps enumerated earlier.⁸ The disincentive to the industry to act in the interest of the society would be reduced sale. Therefore, a realistic approach has been recommended through legislative or regulating action to force timely, complete and unbiased reporting of vital clinical trial results.⁸

The institutions′ conflict of interest may be financial gain or enhanced reputation. The institutional review board (IRB) can effectively take care of these conflicts of interest. Hence, the IJO editorial board insists on IRB clearance for all original articles submitted for possible publication. Most of the conflict of interest is taken care of by this procedure.

A reviewer′s conflict of interest may be financial if he/she is involved in the development of the products of the trial. Some of the reviewers may be having a strong bias on a particular topic which can influence the review process and the bias can be reflected in the comments in either direction. If the reviewers feel that he / she has conflict of interest in any particular article, they should decline to review the article. Giving favorable comments to a friend′s article and unfavorable comments to a researcher whom the reviewer dislikes, is again conflict of interest and the review should be declined. Sometimes reviews have been purposely delayed so that the reviewers can submit and get their data published earlier than the article they are reviewing. This, as well as, sharing the data of the reviewed article before publication with anyone else amounts to conflict of interest and is unethical. Any conflict of interest of the reviewer should be disclosed to the editor; however, this information is confidential and not published in the journal. The best approach is to withdraw themselves from the review process of any particular article with conflict of interest.

The editorial board members, if either themselves or their family members have any conflict of interest in relation to the product involved in any trial, should disqualify themselves from handling the editorial process of related articles. This criterion holds true even for editors, who take the final decision about the fate of a particular article. Transparency in the entire editorial process limits the influence of conflict of interest to the minimum possible level. The IJO editorial office is trying to make the review process completely transparent to keep conflict of interest at bay in the publication process.