Association of Trial Outcome and Funding Source

Approval of new drugs requires that clinical trials be transparent. Drugs are approved based on these trials, and agents may become the standard of care dependent on trial results. The fact that unfounded specialist opinions of trial results may also be raised to the guideline level is a relatively new area of concern. Replication of study results by other investigators is critical, so the recording and publication of trial data are paramount. Peer review is key, and review that occurs post publication is possibly the most important when numerous reviewers can then evaluate a trial’s weaknesses in analysis and interpretation. Publication bias is an element that may also compromise the integrity of published literature. A trial in which a new drug is found to be as effective as placebo, or more effective than an existing agent, may be more likely to be published. This is the reason increased availability of trial results is being attempted. Beginning in September 2008, the US Food and Drug Administration Amendments Act of 2007 (FDAAA) required that trial results be made available to the public. As an example, federal law now requires that all federally funded trials be registered on an open registry such as ClinicalTrials.gov, and journals may not publish results if the trials have not been registered. Generally, excluding phase 1 trials, enrollment and outcomes information from trials of drugs, biologics, and devices must appear in an open database within a year of the trial’s completion, even if these results have not been published. A recent study documented the outcomes of studies and association with their funding source that were listed in ClinicalTrials.gov. This registry was established in 1999 in response to concerns regarding the lack of transparency in trials. In this study, safety and efficacy trials for lipid-lowering agents, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators were examined that were conducted between 2000 and 2006. Over 500 studies were included. Among 546 studies, 346 (63%) were primarily funded by industry, 126 (23%) by nonprofit or nonfederal organizations, and 74 (14%) by government sources. Overall, 362 (66.3%) studies had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 71.9% for nonprofit or nonfederal organization-funded trials, and 50% of trials funded by government sources. Trials funded by industry were also more likely to be phase 3 or 4 studies and less likely to be published within 2 years of study completion. A systematic literature review has shown that industry-funded studies are 4 times more likely to report findings supportive of their product than are studies with no financial interests. This study documents several limitations based on funding source. Researchers involved in studies that were funded by either nonprofit or for-profit backing often did not comply with requirements for trial registration and results publication. Use of registries such as ClinicalTrials.gov for trial reporting should improve transparency, however users should keep in mind that there is still difficulty in determining whether the conduct and published outcomes of trials on these registries were inordinately influenced by commercial interests.