The study concluded that of 78 publications of trials in which the FDA found significant violations, only three (4%) mentioned the objectionable conditions or practices found during the inspection. The researchers also did not publish any corrections, retractions, expressions of concern, or other comments acknowledging the issues identified by the inspections.
The problems uncovered by the FDA also ran the gamut from falsified data to failure to protect patients. The researchers from New York University identified 57 published clinical trials for which an FDA inspection had found significant evidence of one or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%).
“Even though several inspection documents reviewed here described major violations of good clinical practice, including allegations of fabrication and other forms of research misconduct, it was rare that objectionable conditions or practices uncovered by the FDA were reflected in the peer-reviewed literature,” study author Charles Seife writes.
The situation also may be worse than what Seife uncovered as his review was limited to a subsection of trials and publically-available documents from the FDA. Seife writes: “The records that the FDA makes available are incomplete and often heavily redacted. The nature of the redactions—and thus, our likelihood of linking a given document to a specific clinical trial—also varied depending on which FDA officer was performing the redaction and the year in which the redactions were performed.”
CROs (contract research organizations) played a part in some of the research investigated, though company names were redacted.
Seife told Outsourcing-Pharma.com that “CROs were, in fact, involved in some of the studies, though it wasn't always apparent which ones. For example, the first document in my collection (DeAbate 483 and EIR) mentions, on p. 10, that ‘All correspondence with the IRB for the Spectracef studies was facilitated by the CRO,’ but the CRO's name was redacted.”
As far as how the industry and FDA should move forward, Seife calls on the agency to do more to protect the public with its findings from the inspections. “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,” he adds.
Currently, however, most of the burden for ensuring research in peer-reviewed literature includes the FDA’s findings falls to the authors of the articles submitted as there is no formal requirement for authors to disclose any adverse findings.
“Journals should require that any such findings be disclosed,” Seife says. “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.”