Published results of industry-funded clinical trials are more likely to be favorable to the drug studied than trials funded by other sources, according to a study from researchers at Children's Hospital Boston. The researchers say their findings point to the need for more public disclosures about clinical drug trials at their outset to reduce the possibility findings from industry funded studies are biased.

The researchers reviewed 546 drug trials conducted between 2000 and 2006 and listed with ClinicalTrials.gov, a comprehensive, web-based federal registry of clinical trials. The analysis focused on five classes of drugs: cholesterol-lowering drugs, antidepressants, antipsychotics, proton-pump inhibitors and vasodilators. The researchers scanned the medical literature for publications associated with each trial, checking four separate databases and contacting trial investigators directly if necessary.

Overall, allowing for a three-year lag time from the completion of the trial, two-thirds of the trials had published results.

The industry-funded trials reported positive outcomes 85 percent of the time, as compared with 50 percent for government-funded trials and 72 percent for trials funded by nonprofits or non-federal organizations. In addition, among the nonprofit/nonfederal trials, those that had industry contributions (nearly half) were more likely than those without to report positive outcomes (85 vs. 61 percent).

Though the researchers acknowledge that pharmaceutical companies are probably more selective about what trials they fund, they say that alone is unlikely to explain the phenomena. “Industry is very good at knowing what they want to study, and industry-sponsored studies are more efficient and well funded,” says Florence Bourgeois, of Children's Division of Emergency Medicine, the study's first author. “But despite these potential biases, this is a stunning result.”

The industry-funded trials were in more advanced phases of study; 89 percent were phase 3 or phase 4, versus just 51 percent of government-funded trials and 65 percent of nonprofit/nonfederally-funded trials. However, even phase 1 and 2 trials funded by industry reported the highest percentage of favorable outcomes.

In addition, industry-funded trials were the least likely to have published results within two years of study completion (32 percent) as compared with trials with no industry contributions (54 percent for government trials, and 56 percent for purely nonprofit/nonfederal trials).

The researchers note that clinical trials can be manipulated in various ways to make the results appear more favorable. Publication bias—a tendency to selectively publish only positive results of a trial, or delay publication of negative results—is one factor.

“While we cannot specifically point to which factors contribute to the association between funding source and positive result reporting, our findings speak to the need for more disclosure of all elements of a study,” says Bourgeois. “Publication bias is likely a contributing factor, but there may be many more, including biases in study design, patient selection, data analysis and results reporting.”

It was hoped that registries like ClinicalTrials.gov, launched in 1999, would reduce publication bias by creating a record for all clinical trials. In addition, in 2005, the International Committee of Medical Journal Editors began requiring that a trial be registered before enrolling patients in order to be considered for publication, thus creating a record of the planned study outcomes before the study's initiation.

In 2007, the U.S. Food and Drug Administration expanded the scope of ClinicalTrials.gov, requiring the sponsors of all drug, biologic and device trials to register their studies upon launch (phase 1 trials excepted).

The researchers argue that if trial protocols are made public in advance, a trial sponsor is less able to manipulate or selectively publish the findings.

“Our main call is for transparency, to enable better understanding of the impact of funding source on the study outcomes, and for all study results - good or bad - to be made available,” says Kenneth Mandl, the study’s senior investigator and an associate professor at Harvard Medical School.