Clinical trials funded by for-profit organizations continue to return more positive outcomes than those funded by not-for-profits, according to a study in today’s Journal of the American Medical Association. Paul Ridker and Jose Torres from Harvard Medical School surveyed more than 300 cardiovascular disease clinical trials conducted since 2000. They found that for-profit-funded trials—those run by for-profit pharmaceutical or device manufacturers—were significantly more likely to favor the treatment being tested over current standards of care. The authors also found that trials using surrogate endpoints return more positive outcomes, too, regardless of funding source. The latter revelation may be of particular interest to those studying Alzheimer disease (AD). Because AD progresses slowly, surrogate markers are often perceived as being an alternative to lengthy, expensive trials designed around clinical endpoints that might take years to reach.

The study suggests that not much has changed since the 1990s, when numerous surveys reported the same for-profit/not-for-profit discrepancy. Ridker, also at Brigham and Women’s Hospital, Boston, and Torres compiled data from 349 high-impact trials published in three of the top-tier journals—The New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association. The authors made this restriction to limit their study to rigorously peer-reviewed data, and they focused on cardiovascular trials because they are common, important from a public health perspective, and because almost equal numbers of these trials were funded by both for- and not-for-profit organizations. The 349 trials covered both drugs and devices.

The authors found that of 324 superiority trials (i.e., those designed to compare treatments against each other), slightly less than half (49 percent) of the 104 trials funded by not-for-profits favored the new treatment over standard of care. Among the 137 trials funded solely by for-profit sources, that number was significantly higher—67.2 percent. Interestingly, those studies jointly funded by for- and not-for-profits had an intermediate outcome—about 56 percent favored the treatment under trial. There was a slightly greater discrepancy for drug-only trials, with 39.5, 54.4, and 65.5 percent of not-for-profit, jointly funded, and for-profit studies, respectively, finding favor with the new drug versus standard of care.

“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,” write the authors. But there are extenuating circumstances to consider. Null or adverse results from for-profit organizations may not appear in the literature, thus skewing the data. For-profit organizations may also be heavily invested in evaluating proven therapies in new understudied populations, suggest the authors, and the probability of success in these trials is likely greater than for trials evaluating brand new therapies. For-profits are also required to repeat trials in order to meet FDA approval criteria, and this might also contribute to the discrepancy, as outcomes from those trials are more likely to be positive, too. But on the other side of the coin, for-profits rarely report that after rigorous evaluation, approved, commonly used agents are actually ineffective—Ridker and Torres found that most, but not all, of these studies are funded by not-for-profits. This latter finding may be related to those for-profit incentives.

On trials using surrogate endpoints (e.g., intravascular ultrasound, quantitative angiography, plasma biomarkers, and functional measures), the authors found that 67 percent of them, however funded, favored the new treatment. In contrast, only 54 percent of trials using clinical endpoints came down in favor of the novel intervention. Surrogate endpoints were also more likely to be used by not-for-profits (47 percent of 104 trials) than for-profits (30 percent of 137 trials). “We believe our observations of differential rates of positive trial reporting on the basis of endpoint selection strongly reinforces the need for physician decision making and Food and Drug Administration approval to remain on the basis of clinical rather than surrogate endpoints,” write the authors.—Tom Fagan

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Primary Papers

  1. . Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005. JAMA. 2006 May 17;295(19):2270-4. PubMed.