When published results are systematically tracked for drug trials registered with ClinicalTrials.gov, those from industry-funded trials are the likeliest to be favourable to the drug in question, report researchers in the August 3, 2010 issue of the Annals of Internal Medicine.
The authors of the article reviewed 546 drug trials conducted between 2000 and 2006 and listed with ClinicalTrials.gov, a comprehensive, web-based registry of clinical trials. 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% of the time, as compared to 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 their greater proportion of favourable outcomes. The industry-funded trials were in more advanced phases of study; 89% were Phase III or Phase IV, versus just 51% of government-funded trials and 65% of nonprofit/nonfederal trials. However, even Phase I and II trials funded by industry reported the highest percentage of favourable outcomes. In addition, industry-funded trials were the least likely to have published results within two years of study completion (32%), as compared to trials with no industry contributions (54% for government trials, and 56% for purely nonprofit/nonfederal trials).
As the researchers discuss in the paper, clinical trials can be manipulated in various ways to make the results appear more favourable. 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 in The New England Journal of Medicine.
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 the use of 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 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 I trials excepted). If trial protocols are made public in advance, a trial sponsor is less able to manipulate or selectively publish the findings, the study researchers argued.
For more information:
Bourgeois FT, Murthy S, Mandl KD. Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov. Ann Intern Med August 3, 2010 153:158-166;