Drug trials funded by industry more likely to publish favorable results

Bourgeois F. Ann Intern Med. 2010;153:158-166.

Researchers at Children’s Hospital Boston found that published clinical results of industry-sponsored drug trials registered with ClinicalTrials.gov are the most likely to be favorable to the drug in question.

In their study, published in the Annals of Internal Medicine, the researchers call for more public disclosure about clinical drug trials at their outset to reduce the possibility of bias in the findings, according to a Children’s Hospital Boston press release.

The research team, led by Florence Bourgeois, MD, MPH, of Children’s Division of Emergency Medicine, and Kenneth Mandl, MD, MPH, laboratory director in the Children’s Hospital Informatics Program, 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 researchers directly if necessary.

‘Stunning result’

Overall, allowing for a 3-year lag time from the completion of the trial, two-thirds of the trials had published results, the press release noted. The industry-funded trials reported positive outcomes 85% of the time, as compared with 50% for government-funded trials and 72% for trials funded by nonprofits or non-federal organizations. In addition, among the nonprofit/non-federal trials, those that had industry contributions (nearly half) were more likely than those without to report positive outcomes (85% vs. 61%). These differences were all statistically significant, according to the press release.

The researchers acknowledged that the pharmaceutical industry was probably more selective in which trials it funded, possibly contributing to their greater proportion of favorable outcomes. “Industry is very good at knowing what they want to study, and industry-sponsored studies are more efficient and well funded,” Bourgeois stated in the release. “But despite these potential biases, this is a stunning result.”

The release also noted that the industry-funded trials were in more advanced phases of study; 89% were phase 3 or phase 4, compared with 51% of government-funded trials and 65% of nonprofit/non-federal trials. However, even phase 1 and 2 trials funded by industry reported the highest percentage of favorable outcomes.

Manipulating studies

In addition, industry-funded trials were the least likely to have published results within 2 years of study completion (32% vs. 54% for government trials and 56% for purely nonprofit/non-federal trials).

The researchers noted that clinical trials can be manipulated in several 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 that has received much attention, as in a well-publicized 2008 study of antidepressants in The New England Journal of Medicine.

“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,” Bourgeois said. “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.”

Registration requirements

The use of registries like ClinicalTrials.gov, launched in 1999, was hoped to reduce publication bias by creating a record for all clinical trials, according to the release. 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 FDA expanded the scope of ClinicalTrials.gov, requiring the sponsors of all drug, biologic and device trials to register their studies upon launch, except for phase I trials.

If trial protocols are made public in advance, a trial sponsor is less able to manipulate or selectively publish the findings, the researchers noted. “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,” Mandl, the study’s senior investigator, stated in the release.