Incomplete Publishing Leads to Bias
“There are a lot of public statements from drug companies saying that they support the registration of clinical trials or the dissemination of trial results, but the devil is in the details,” noted Deborah Zarin, M.D., director of ClinicalTrials.gov.
“Our current evidence base contains incomplete and questionable evidence,” Dr. Wieseler said. “We know that not all studies that investigate drugs are published. The published literature tends to overestimate benefits and underestimate harms because positive studies are published more often and earlier than negative studies. Therefore, the picture of a drug in the published literature may be biased.”
A paper published this August in Annals of Internal Medicine by researchers from the U.S. and Canada looked at 546 drug trials registered on ClinicalTrials.gov. Sixty three percent, or 346 of them, were funded by the drug industry. The remaining 200 were paid for by government or nonprofit organizations.
Study authors found that more than 85% of industry-funded trials in their sample posted favorable outcomes and were four times more likely to report findings that favored their drug. The investigators reached the conclusion that studies funded by industry were less likely to be published within two years of study completion and were more likely to report positive outcomes than trials funded by other sources.
“We did this study in order to determine whether there is an inherent bias because pharmaceutical companies fund trials on products in which they have a financial interest,” said study co-author Kenneth Mandl, M.D., of Children's Hospital, Boston. “The most reassuring result would have been that the rate of favorable outcomes would be the same regardless of funding sources.”
Dr. Zarin pointed out that most of the trials used in this study were registered prior to the enactment of FDAAA and therefore were not covered by newer, more stringent registration requirements.
“It is clear, however, that some level of selective publication is occurring so that the public as well as medical experts only have access to a biased sample of studies for any given class of drugs,” Dr. Zarin conceded. “It is therefore urgent that all sponsors of trials, whether government, industry, or others, make strenuous efforts to implement the requirements under FDAAA.”