Drug Clinical Trials BiasedNov 28, 2008 | Parker Waichman LLP A quarter of all trials submitted to the U.S. Food and Drug Administration (FDA) for new drug applications are still unpublished five years after completion. What's more, discrepancies exist between what drug trials are reviewed by the FDA, and which ones are published. These are the conclusions of a recent study published by the journal PLoS Medicine, a publication of the Public Library of Science.
According to a press release reprinted by Science Daily, inconsistencies appeared between what was submitted to the FDA and what was subsequently published. As a result, what was published generally presented the drugs—in medical literature geared to medical professionals—in a positive light. Some of the differences between the submitted and published trials included outcome additions or deletions, changes in the statistical significance of reported outcomes, and changes in overall trial conclusions, the release said.
To reach these conclusions, a team led by Lisa Bero from the University of California San Francisco reviewed the publication status of all 164 efficacy trials conducted for 33 new drug applications (NDA) for new molecular entities approved by the FDA in 2001-2002. Bero and her team compared the FDA reviews against published articles and found only 78 percent of the trials were published and drug trials receiving positive outcomes were likelier to be published. Of 179 outcomes, 41 were omitted from the papers. NDAs—which give information on a drug from lab and animal studies through clinical trials—must be submitted to the FDA by a drug’s sponsor before a new drug can receive approval in the U.S.
The team found that of the 43 primary outcomes reported in the NDAs which provided no statistically significant benefit for the test drug, only about half were included in the papers. The authors also found that when a difference between the NDA and the paper occurred, the test drug was generally presented in a favorable light, and when conclusions differed, the positive conclusion was published. The team did not look into the reason for the discrepancies, and did not determine if the changes were initiated by a drug sponsor, author, or journal. In response to their findings determining “publication bias and selective reporting,” the team found that "the information that is readily available in the scientific literature to health care professionals is incomplete and potentially biased.
In an editorial accompanying the study in PLos, An-Wen Chan, wrote that, “Misreporting of trials can be difficult to detect without access to detailed documents beyond what is currently available on registries and results databases. Only with full transparency can the validity of a randomized trial be judged.” An-Wen Chen was not involved in the study but was a scientist with the World Health Organization’s (WHO) International Clinical Trials Registry Platform and is currently at the Mayo Clinic.