A new study by invetigators from Children’s Hospital, Boston, finds that when published results are systematically tracked for drug trials registered with ClinicalTrials.gov, those from industry-funded trials are the likeliest to be favorable to the drug in question. As a result of the study, published in the Annals of Internal Medicine, the researchers are calling for more public disclosure about clinical drug trials at their outset to reduce the possibility of bias in the findings.
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.
Overall, allowing for a 3-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% of the time, compared with 50% for government-funded trials and 72% for trials funded by nonprofits or nonfederal 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% versus 61%). These differences were all statistically significant.
The researchers acknowledge that the pharmaceutical industry was probably more selective in which trials it funded, helping to account for the greater proportion of favorable outcomes.
The industry-funded trials were in more advanced phases of study—89% were phase 3 or phase 4, versus just 51% of government-funded trials and 65% 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 2 years of study completion (32%), compared with trials with no industry contributions (54% for government trials, and 56% for purely nonprofit/nonfederal trials).
“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 Florence Bourgeois, MD, MPH, from the children’s division of emergency medicine at Children’s Hospital Boston. “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. In addition, in 2005, the Internal 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 Food and Drug Administration expanded the scope of ClinicalTrials.gov, requiring the sponsors of all drugs, biologic, and device trials to register their studies upon launch (phase 1 trials excepted).
The researchers in this study argue that a trial sponsor is less able to manipulate or selectively publish findings if trial protocols are made public in advance.
Source: Children’s Hospital Boston
