 Bekelman, J. E., Li, Y., & Gross, C. P. (2003). Scope and impact of financial conflicts of interest in biomedical research: a systematic review. Jama, 289(4), 454-465. Context Despite increasing awareness about the potential impact of financial conflicts of interest on biomedical research, no comprehensive synthesis of the body of evidence relating to financial conflicts of interest has been performed.
Objective To review original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research.
Data Sources Studies were identified by searching MEDLINE (January 1980-October 2002), the Web of Science citation database, references of articles, letters, commentaries, editorials, and books and by contacting experts.
Study Selection All English-language studies containing original, quantitative data on financial relationships among industry, scientific investigators, and academic institutions were included. A total of 1664 citations were screened, 144 potentially eligible full articles were retrieved, and 37 studies met our inclusion criteria.
Data Extraction One investigator (J.E.B.) extracted data from each of the 37 studies. The main outcomes were the prevalence of specific types of industry relationships, the relation between industry sponsorship and study outcome or investigator behavior, and the process for disclosure, review, and management of financial conflicts of interest.
Data Synthesis Approximately one fourth of investigators have industry affiliations, and roughly two thirds of academic institutions hold equity in start-ups that sponsor research performed at the same institutions. Eight articles, which together evaluated 1140 original studies, assessed the relation between industry sponsorship and outcome in original research. Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals.
Conclusions Financial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways."This comprehensive review of the literature confirms that financial relationships among industry, scientific investigators, and academic institutions are pervasive. About one fourth of biomedical investigators at academic institutions receive research funding from industry. One study reported that lead authors in 1 of every 3 articles published hold relevant financial interests, while another reported that approximately two thirds of academic institutions hold equity in 'start-up' businesses that sponsor research performed by their faculty."
"Despite the prevalence of these relationships and the broad concerns they have generated, a relative paucity of data has been published describing the impact of financial ties on biomedical research. Although only 37 articles met inclusion criteria, evidence suggests that the financial ties that intertwine industry, investigators, and academic institutions can influence the research process. Strong and consistent evidence shows that industry-sponsored research tends to draw pro-industry conclusions. By combining data from articles examining 1140 studies, we found that industry-sponsored studies were significantly more likely to reach conclusions that were favorable to the sponsor than were nonindustry studies."Perlis, R. H., Perlis, C. S., Wu, Y., Hwang, C., Joseph, M., & Nierenberg, A. A. (2005). Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. American Journal of Psychiatry, 162(10), 1957-1960. OBJECTIVE: Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors’ knowledge. METHOD: The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. RESULTS: Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. CONCLUSIONS: Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.
Glode, E. R. (2002). Advising Under the Influence: Conflicts of Interest Among FDA Advisory Committee Members. Food & Drug LJ, 57, 293. Advisers on Vaccines Often Have Conflicts, Report Says; by Gardiner Harris, New York Times: New York Edition, December 18, 2009, page A28. Representative Rosa DeLauro, a Connecticut Democrat who said she had long been a supporter of the C.D.C., said: “That is why I am so concerned about this report issued by the inspector general exposing serious ethics violations within the C.D.C. All members of the federal advisory committees, whose recommendations direct federal policy, should be without conflict of interest.”OIG Final Report: CDC's Ethics Program for Special Government Employees on Federal Advisory Committees, OEI-04-07-00260, Daniel R. Levinson, Inspector General, Department of Health & Human Services, December 2009. DeLong, G. (2012). Conflicts of interest in vaccine safety research. Accountability in research, 19(2), 65-88. Conflicts of interest (COIs) cloud vaccine safety research. Sponsors of research have competing interests that may impede the objective study of vaccine side effects. Vaccine manufacturers, health officials, and medical journals may have financial and bureaucratic reasons for not wanting to acknowledge the risks of vaccines. Conversely, some advocacy groups may have legislative and financial reasons to sponsor research that finds risks in vaccines. Using the vaccine-autism debate as an illustration, this article details the conflicts of interest each of these groups faces, outlines the current state of vaccine safety research, and suggests remedies to address COIs. Minimizing COIs in vaccine safety research could reduce research bias and restore greater trust in the vaccine program.Sterne, J. A., Egger, M., & Smith, G. D. (2001). Investigating and dealing with publication and other biases in meta-analysis. Bmj, 323(7304), 101-105. Studies that show a significant effect of treatment are more likely to be published, be published in English, be cited by other authors, and produce multiple publications than other studies. Such studies are therefore also more likely to be identified and included in systematic reviews, which may introduce bias. Low methodological quality of studies included in a systematic review is another important source of bias.
All these biases are more likely to affect small studies than large ones. The smaller a study the larger the treatment effect necessary for the results to be significant. The greater investment of time and money in larger studies means that they are more likely to be of high methodological quality and published even if their results are negative. Bias in a systematic review may therefore become evident through an association between the size of the treatment effect and study size—such associations may be examined both graphically and statistically.Bastian, H. (2006). ‘They would say that, wouldn't they?’A reader's guide to author and sponsor biases in clinical research. Journal of the Royal Society of Medicine, 99(12), 611-614. Lee, K., Bacchetti, P., & Sim, I. (2008). Publication of clinical trials supporting successful new drug applications: a literature analysis. PLoS medicine, 5(9), e191. Over half of all supporting trials for FDA-approved drugs remained unpublished ≥ 5 y after approval. Pivotal trials and trials with statistically significant results and larger sample sizes are more likely to be published. Selective reporting of trial results exists for commonly marketed drugs. Our data provide a baseline for evaluating publication bias as the new FDA Amendments Act comes into force mandating basic results reporting of clinical trials. Wager, E. (2007). Authors, ghosts, damned lies, and statisticians. PLoS medicine, 4(1). Since the earliest peer-reviewed publications of the late 17th century, conventions about the authorship of scientific papers—which were generally anonymous and attributed to the sponsor (in those days, usually the church or the king)—have evolved considerably. Readers now want to know not only who paid for the research but also who did the work. Transparency (i.e., full disclosure) is now considered a moral responsibility, and many medical journals have introduced mechanisms for increasing transparency. The International Committee of Medical Journal Editors (ICMJE) has also issued guidance on who qualifies for authorship, and their criteria have been updated and augmented several times in response to several authorship scandals. Yet problems with authorship persist.Ioannidis, J. P. (2005). Why most published research findings are false. PLoS medicine, 2(8), e124. There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.Taubes, G., & Mann, C. C. (1995). Epidemiology faces its limits. Science, 269(5221), 164-169. Topol, E. J. (2004). Failing the public health—rofecoxib, Merck, and the FDA. New England Journal of Medicine, 351(17), 1707-1709. Unfortunately, such a trial was never done. The FDA has the authority to mandate that a trial be conducted, but it never took the initiative. Instead of conducting such a trial at any point — and especially after the FDA advisory committee meeting in 2001 — Merck issued a relentless series of publications, beginning with a press release on May 22, 2001, entitled “Merck Reconfirms Favorable Cardiovascular Safety of Vioxx” and complemented by numerous papers in peer-reviewed medical literature by Merck employees and their consultants. The company sponsored countless continuing medical “education” symposiums at national meetings in an effort to debunk the concern about adverse cardiovascular effects.
Each time a study was presented or published, there was a predictable and repetitive response from Merck, which claimed that the study was flawed and that only randomized, controlled trials were suitable for determining whether there was any risk. But if Merck would not initiate an appropriate trial and the FDA did not ask them to do so, how would the truth ever be known?
Horrobin, D. F. (2001). Something rotten at the core of science?. Trends in Pharmacological Sciences, 22(2), 51-52.
The US Supreme Court has recently been wrestling with the issues of the acceptability and reliability of scientific evidence. In its judgement in the case of Daubert versus Merrell Dow, the Court attempted to set guidelines for US judges to follow when listening to scientific experts. Whether or not findings had been published in a peer-reviewed journal provided one important criterion. But in a key caveat, the Court emphasized that peer review might sometimes be flawed and therefore this criterion was not unequivocal evidence of validity or otherwise. A recent analysis of peer review adds to this controversy by identifying an alarming lack of correlation between reviewers' recommendations.
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