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
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
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.
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
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
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.”
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.