In the present era of evidence-based medicine, the authenticity of published material is of paramount importance. However, conflict of interest, intentional or unintentional, may be a source of risk for the readers in the accurate judgment of the clinical utility of a published trial.
What is conflict of interest? A working definition for conflict of interest with regard to publishing research results, as suggested by Rumsay,1 is that 'conflict of interest is a situation in which personal benefit or economic gain (either directly or indirectly via an individual's research program, institution or individual reputation) takes priority over clarity or accuracy of the reporting of the research.' In research, review and publication process, the term commonly interchanged with 'conflict of interest' is 'bias.'
Conflict of interest may be due to financial or nonfinancial reasons. The nonfinancial reasons for researchers may be the pressures related to enhancing reputation, academic progress, ego satisfaction, recognition by peers, more grants for research, media attention and increased patient referrals.234 These factors do not usually lead to distortion of a trial. However, the financial reasons are more disturbing, especially when trials for drugs or equipments are sponsored by companies. The researchers may be offered a large monetary incentive while the company itself has a lot at stake. The outcome of the study may influence the approval of the product concerned by the food and drug administration (FDA) or may result in increased sales in the market; considering this, the fear of conflict of interest in publication is not unfounded. There are many examples in literature. Davidson reported that the chances of favorable outcome with a therapy over the standard therapy was higher if the trial was funded by the manufacturer of the new therapy.5 Cho et al. pointed out that articles from symposiums sponsored by a single company had more favorable outcome of the articles involving a sponsor's drug than the articles without company support.6 Stelfox et al. found that authors reporting better safety with calcium-channel blockers had more chance of a financial relationship with the manufacturer of the drug than those authors who did not report increased safety with calcium-channel blockers.7 A report by Friedburg et al. is startling; they stated that only 5% had unfavorable outcomes with manufacturer-sponsored studies involving cancer drugs, whereas 38% had unfavorable outcome if the study was funded by nonprofit agencies.8 This outcome is not a surprise if you realize that the average cost of developing one new drug is estimated to be between US$300 million and US$600 million.9 The industry spends for drug trials almost 70% of the total money spent in the US, and the National Institute of Health (NIH) contributes less than half of this amount.9
There is a paradigm shift in the conduction of drug trials. Earlier trials used to be institution based as the companies lacked the in-house facilities to design a study. Institutions had the required patients who could be the study subjects, and publications through an institution had the added advantage of enhanced prestige and acceptability. However, the drug companies these days prefer to employ a good researcher to design the study. Subsequently, instead of approaching institutions for the conduct of research, they approach for-profit organizations such as contract-research organizations (CROs) and site-management organizations (SMOs). The benefit in terms of time frame is substantial as the institutions have their own lengthy procedures before the study is approved by their local body. The research activity is not the primary activity of the institutions, whereas for CROs and SMOs their primary activity is facilitation of the smooth conduct of trials. A delay in FDA approval of a drug by a single day can cause a loss of approximately US$ 1.3 million to the companies.9
These days, many clinical trials are being conducted in India by companies through CROs and SMOs. Each participating institution should be careful while accepting to participate in these trials. In these company-sponsored trials, conflict of interest may creep in. The trial design may be faulty due to bias. Bero et al.10 have enumerated various methods companies adopt to produce an outcome in favor of their product. Usually, companies prepare the study design without any input from the participating clinicians, who are then asked to follow it without any liberty to make changes. I have myself suggested some drug trials to many companies in India, but none have come forward for fear of reduced sales in case of an adverse outcome.
Some of the examples of faulty designs may be testing of drugs on healthier population with milder disease and fewer coexisting conditions so that the drug can be proved to be effective with fewer side effects.10 Another example is a nonsteroidal anti-inflammatory drug trial on a relatively younger age group for side effects, although this drug may eventually be used in the higher-age group.11 The trial drug may be compared with the standard drug of insufficient dose to prove the efficacy of the new drug.10 Inappropriate route of administration may be used to prove the inferiority of an established drug; Johansen et al.12 showed this in most of the trials demonstrating fluconazole to be superior to orally administered amphotericin B, and it is well known that oral amphotericin B is poorly absorbed.
Data analysis by companies raises many serious doubts. Only favorable data may be presented, as the companies have full control of the data. Many trials having an unfavorable outcome for a particular sponsoring company may not be submitted for publication at all. Sometimes, only truncated data - data that is favoring the company's product - may be published. Authorship is also a contentious issue. Ghost authors and gift authors are quite common in the publication of company-sponsored trials.13
When so much is at stake, the participating researchers/ institutions should be vigilant before entering into a company-sponsored trial. The Indian Journal of Ophthalmology (IJO) is therefore clear in its policy of disclosure. The IJO expects full disclosure by all the authors of any financial assistance or conflict of interest with regard to the submitted manuscript for possible publication. This disclosure information is printed along with the article in IJO. This gives a fair chance to the readers to interpret any article in the right perspective.
1. Rumsey TS. One editor's views on conflict of interest J Anim Sci. 1999;77:2379–83
2. Korn D. Conflicts of interests in biomedical research JAMA. 2000;284:2234–7
3. Cohen JJ. Trust us to make a difference: Ensuring public confidence in the integrity of clinical research Acad Med. 2001;76:209–14
4. Constantian MB. Conflicts of interest in medical writing and the concept of disclosure Plast Recconstr Surg. 2000;105:796–7
5. Davidson RA. Source of funding and outcome of clinical trials J Gen Intern Med. 1986;1:155–8
6. Cho MK, Bero LA. The quality of drug studies published in symposium proceedings Ann Intern Med. 1996;124:485–9
7. Stelfox HT, Chua G, O'Rourke K, Destsky AS. Conflict of interest in the debate over Calcium- channel antagonists N Engl J Med. 1998;338:101–6
8. Freiedberg M, Saffran B, Stinson TJ, Nelson W, Bennet CL. Evaluation of conflict of interest in economic analyses of new drugs used in oncology JAMA. 1999;282:1453–7
9. Bodenheimer T. Uneasy alliance: Clinical investigators and the pharmaceutical industry N Engl J Med. 2000;342:1539–44
10. Bero LA, Rennie D. Influences on the quality of published drug studies Int J Technol Assess Health Care. 1996;12:209–37
11. Rochon PA, Berger PB, Gordon M. The evolution of clinical trials: Inclusion representation CMAJ. 1998;159:1373–4
12. Johansen HK, Gotzsche PC. Problems in the design and reporting of trials of antifungal agents encountered during meta- analysis JAMA. 1999;282:1752–9
13. Nayak BK, Moreker S, Pawar D. ABC of authorship: Aims, banes and credits Indian J Ophthalmol. 2005;53:223–4