FDA infractions rarely reflected in journal publications

When clinical trial sites using human subjects for biomedical research are found to have significant problems by the Food and Drug Administration (FDA), these findings are seldom reflected in the peer-reviewed literature that stems from the trials, according to an article published online Feb. 9 by the JAMA Internal Medicine (JAMA IM).

In 2013, the FDA conducted 644 clinical site inspections as part of the drug approval process, according to the study’s author, Charles Seife, MS, a professor at the Arthur L. Carter Institute of Journalism at New York University, who conducted the research along with his students.

In its inspections, the agency classifies violations based on severity in one of three ways—with the most severe infractions earning “official action indicated” (OAI) designation. These infractions can stem from practices like failure to report adverse drug reactions to the appropriate bodies to submission of false information. Practices like these, Seife wrote, can raise questions about the validity of a trial’s data.

In the review, Seife and his students sought to identify publications that described clinical trials the FDA deemed had an OAI violation, to describe those violations and to determine if the published article had acknowledged the trial’s violation.

Seife identified 57 published clinical trials that were identified by the FDA as having one or more significant problems worthy of an OAI ranking.

The researchers found that 39 percent (22 trials) had falsification or submission of false information; 25 percent (14 trials) had problems with adverse event reporting; 74 percent (42 trials) had protocol violations; 61 percent (35 trials) had inadequate or inaccurate recordkeeping; 53 percent (30 trials) failed to protect the safety of patients and/or had issues with oversight or informed consent; and 35 percent (20 trials) had violations that were not categorized.

Seife found that only 3 of the 78 publications that stemmed from the reviewed clinical trials mentioned the objectionable conditions found during the FDA inspections. Further, no retractions or other comments acknowledging the infractions or concerns found by the inspections were published.

“The findings presented in this study should give us pause,” Seife wrote.  “This investigation has found numerous studies for which the FDA determined there was significant evidence of fraudulent or otherwise problematic data. Such issues raise questions about the integrity of a clinical trial, and mention of these problems is missing from the relevant peer-reviewed literature.”

The FDA does not notify journals of its OAI findings, nor does it notify the general public of any research misconduct identified, Seife wrote.

In an associated editorial, Robert Steinbrook, MD, of the Yale School of Medicine, and Rita F. Redberg, MD, of the University of California San Francisco, editor-at-large and editor-in-chief, respectively, of JAMA IM, called the FDA and the journals to task for their responsibility to maintain and improve trust in medical literature.

“Journals should expect that investigators and sponsors of clinical trials would promptly notify them of substantial findings from FDA and other regulatory agency inspections and modify their reports of clinical trials as needed, either before or after publication,” wrote Steinbrook and Redberg.