Surveys of randomized trials published between 1990 and 2000 raised awareness in the medical community that trials funded by for-profit (FP) organizations were more likely to report positive findings than those funded by not-for-profit (NFP) organizations. These surveys raised questions regarding the design and conduct of industry funded clinical trials as well as certain ethical concerns, according to background information in the article. Whether recognition of these concerns has affected contemporary clinical trials was unknown.
Paul M. Ridker, M.D., of Brigham and Women's Hospital, and Jose Torres, B.A., of Harvard Medical School, Boston, analyzed outcomes of 324 cardiovascular clinical trials published between 2000 and 2005 in JAMA, The Lancet, and the New England Journal of Medicine, stratifying the results on whether the trial was funded by for-profit or not-for-profit organizations and if the trial outcome favored newer treatments over the standard of care. Of the 324 trials, 21 cited no funding source.
Overall, 58.6 percent of the 324 trials reported evidence significantly favoring newer treatments, while 34.6 percent reported no significant difference between therapies, and 6.8 percent reported evidence significantly favoring standard of care. Among not-for-profit trials, 49 percent of 104 reported evidence significantly favoring newer treatments, whereas 51 percent either significantly favored standard of care or showed no difference.
Among for-profit trials, 67.2 percent of 137 reported evidence significantly favoring newer treatments with 32.8 percent reporting data favoring standard of care or no difference. The proportion of trials significantly favoring new treatments for studies jointly funded by for-profit and not-for-profit organizations was approximately midway between these 2 values (56.5 percent).
For 202 randomized trials evaluating drugs, the proportions favoring newer agents were 39.5 percent for not-for-profit, 54.4 percent for jointly sponsored, and 65.5 percent for for-profit trials. For the 38 randomized trials evaluating cardiovascular devices, the proportions favoring newer treatments were 50.0 percent, not-for-profit; 69.2 percent, jointly funded; and 82.4 percent, for-profit trials.
Regardless of funding source, clinical trials using surrogate end points, such as intravascular ultrasound, quantitative angiography, plasma biomarkers, and functional measures were more likely to report positive findings (67.0 percent) than were clinical trials using clinical end points (54.1 percent).
"As suggested in surveys of randomized trials published prior to 2000, these contemporary data appear to show that incentives surrounding for-profit organizations have the potential to influence clinical trial outcomes. Previous attempts to explain this phenomenon have focused largely on design bias, interpretation bias, data suppression, and differential data quality," the authors write.
" … we believe there are additional issues that help to explain, in part, the observed results. For example, when the first trial report of a truly novel therapy is null or negative, it becomes less likely that any funding source will support subsequent studies. On the other hand, when the first trial of a truly novel therapy is positive, the likelihood of further trials is increased. These subsequent trials understandably and perhaps appropriately are more likely to be funded by for-profit organizations," the researchers write.
(JAMA. 2006;295:2270-2274. Available pre-embargo to the media at www.jamamedia.org)
Journal
JAMA