Financial ties between researchers and companies that make the drugs they are studying are independently associated with positive trial results, suggesting bias in the evidence base, concludes a University of California study.
Relationships with industry are common among investigators of randomised clinical trials (RCTs) – raising concerns about the effect that financial ties may have on the evidence base. But studies investigating these relationships have been conflicting.
So, a team of US based researchers led by Salomeh Keyhani, associate professor of general internal medicine, University of California – San Francisco, set out to investigate the association between financial ties of principal investigators and study outcomes in a random sample of 195 drug trials published in 2013. They focused on trials that examined the effectiveness of drugs, because these studies have a high impact on both clinical practice and healthcare costs.
More than half (58%) of principal investigators had financial ties to the drug industry – including travel expenses, honorariums, payment for advisory work, or stock ownership. The results show that trials authored by principal investigators with financial ties to drug manufacturers were more likely than other trials to report favourable results.
Even after accounting for factors that may have affected the results, such as funding source and sample size, financial ties were still significantly associated with positive study outcomes.
The authors point to possible mechanisms linking industry funding, financial ties, and trial results such as bias by selective outcome reporting, lack of publication, and inappropriate analyses.
They stress that their analysis is observational and cannot be used to draw conclusions about causation, but say, given the importance of industry and academic collaboration in advancing the development of new treatments, “more thought needs to be given to the roles that investigators, policy makers, and journal editors can play in ensuring the credibility of the evidence base.”
More research is certainly needed to identify how industry funding and financial ties could influence trial results, say Andreas Lundh from the University of Southern Denmark and Lisa Bero from the University of Sydney in a linked editorial.
They urge trial authors to share their data and participate in industry funded trials only if data are made publicly available – and suggest journals could help by rejecting research by authors who are unwilling to share their data and by penalising authors who fail to disclose financial ties.
The role of sponsors, or companies with which authors have ties, in the research must also be transparent.
In the meantime, trials with industry funding or authors with financial ties “should be interpreted with caution until all relevant information is fully disclosed and easily accessible,” they conclude.
Abstract
Objective: To examine the association between the presence of individual principal investigators’ financial ties to the manufacturer of the study drug and the trial’s outcomes after accounting for source of research funding.
Design: Cross sectional study of randomized controlled trials (RCTs).
Setting: Studies published in “core clinical” journals, as identified by Medline, between 1 January 2013 and 31 December 2013.
Participants: Random sample of RCTs focused on drug efficacy.
Main outcome measure: Association between financial ties of principal investigators and study outcome.
Results: A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers’ fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1.4 to 7.9).
Conclusions: Financial ties of principal investigators were independently associated with positive clinical trial results. These findings may be suggestive of bias in the evidence base.
Authors
Rosa Ahn, Alexandra Woodbridge, Ann Abraham, Susan Saba, Deborah Korenstein, Erin Madden, W John Boscardin, Salomeh Keyhani
[link url="http://www.bmj.com/company/wp-content/uploads/2017/01/financial-ties-The-BMJ.pdf"]BMJ material[/link]
[link url="http://www.bmj.com/content/356/bmj.i6770"]BMJ abstract[/link]
[link url="http://www.bmj.com/content/356/bmj.j176"]BMJ editorial[/link]