Every year, the FDA inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However according to an investigation published in the JAMA Internal Medicine, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature.
Charles Seife, a New York University journalism professor conducted literature research “to identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature.” He reviewed 78 published papers on clinical trials with which the Food and Drug Administration (FDA) labeled “official action indicated” (OAI), meaning the agency found objectionable conditions or practices significant enough to warrant regulatory action, yet he found that only three of the papers mentioned the OAI status of the trials. The violations included researchers falsifying data and occurrences where clinical trial participants should have been ruled ineligible. His finding was published in the JAMA Internal Medicine “Research Misconduct Identified by the US Food and Drug Administration Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature.”
“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 typically notify journals when a site participating in a published clinical trial receives an OAI inspection, nor does it generally make any announcement intended to alert the public about the research misconduct that it finds. The documents the agency discloses tend to be heavily redacted. As a result, it is usually very difficult, or even impossible, to determine which published clinical trials are implicated by the FDA’s allegations of research misconduct.” Seife concluded “When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.”
In one of the illustrative cases he reviewed, a case involving a trial of a chemotherapy regimen, the researcher eventually pleaded guilty to fraud and was sentenced to prison after poor results were hidden and a patient died from the treatment (United States of America v. Paul H. Kornak, 03-cr-00436 (Northern District of New York). “Although this episode is described in detail in FDA documents as well as court documents, none of the publications in the peer-reviewed literature associated with the chemotherapy study in which the patient died have any mention of the falsification, fraud, or homicide. The publications associated with two of the three other studies for which the researcher falsified documents also do not report on the violations,” according to the study.
“The FDA has legal as well as ethical responsibilities regarding the scientific misconduct it finds during its inspections. When the agency withholds the identity of a clinical trial affected by scientific misconduct, it does so because it considers the identity to be confidential commercial information, which it feels bound to protect. However, failing to notify the medical or scientific communities about allegations of serious research misconduct in clinical trials is incompatible with the FDA’s mission to protect the public health. Such allegations are relevant to include in the peer-reviewed literature on which physicians and other medical researchers rely to help them choose treatments that they offer to patients and other research participants.”
The article concludes by saying “To better serve the public health, the FDA should make unredacted information about its findings of research misconduct more readily available. The agency should make sure that any substantial evidence of misconduct is available to editors and readers of the scientific literature. One possible mechanism for this would be to use the national clinical trials database: any OAI inspection affecting a trial site should be promptly noted at http://www.clinicaltrials.gov. The FDA should also create a website or a publicly available database that lists all OAI-rated inspections of clinical sites and provides links to copies of the relevant, unredacted, inspection-related documents.”
“The FDA should be more transparent about its findings of research misconduct; however, most of the burden for ensuring the integrity of the research in the peer-reviewed literature falls to the authors of the articles submitted to peer-reviewed journals. Currently, there is no formal requirement for authors seeking to publish clinical trial data to disclose any adverse findings noted during FDA inspections. Journals should require that any such findings be disclosed. Voluntary disclosures are never foolproof, but, as with conflict-of-interest statements, requiring authors and journals to be forthcoming about significant departures from good clinical practice will help raise the standard for the reporting of research toward greater transparency.”