FDA Not Reporting Clinical Trial Fraud, Misconduct: Study

Although the FDA frequently finds fraud and other forms of research misconduct in clinical trials conducted by drug manufacturers, a new investigative report highlights how the public and medical community are almost never informed about these problems. 

A study published this month by the medical journal JAMA Internal Medicine found that only 4% of objectionable conditions or practices revealed by the FDA that take place during clinical drug trials ever see the light of day.

In many cases, these clinical trials may have formed the basis for the approval of drugs currently on the market, raising concerns about the regulatory oversight provided by the agency.

The research was conducted by Charles Seife, of the Arthur L. Carter Institute of Journalism at New York University, involving a cross-sectional analysis of publicly available documents describing FDA inspections of clinical trial sites, looking for those where the FDA found significant evidence of objectionable conditions or practices.

Unfortunately, due to heavy redacting, the actual products involved are seldom identified, as drug names and formulations are almost always blacked out.

From 1998 to 2013, Seife found 57 published clinical trials where the FDA inspection found significant evidence of wrongdoing. These studies found their way into 78 publications.

The most commonly cited problem was failure of clinical trial protocols, which occurred in three-quarters of the studies reported. However, most appeared to have multiple violations, including inadequate or inaccurate record keeping in 61% of the trials, falsification or submission of false information in 22 (39%) of the trials, and a failure to protect the safety of patients in more than half ( 53%) of the trials.

Despite the findings, when Seife looked to see what was made known to the scientific community, he found very little.

“Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection,” Seife reports. “No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.”

The three articles that actually mention the violations included one where none of the individuals enrolled at one of the study sites actually met the inclusion criteria. Seife reports that in that case, the researcher fabricated chest radiographs of participants, among other forms of misconduct.

Extremely Objectionable Clinical Trial Practices Unreported

Surprisingly, it is not a case where only the worst violations get reported. There were numerous instances of gross misconduct in clinical trials that made it to print with no mention of the problems discovered, according to the findings.

One drug that was mentioned by name was the blood thinner Xarelto (rivaroxaban). Out of 16 FDA inspections, eight uncovered signs of wrongdoing, often extremely serious. These included the falsification of data, the discarding of medical records, unauthorized unblinding (where researchers knew which patients were getting the drug or the placebo), and other problems. The entire study, RECORD 4, was determined to be unreliable by the FDA. However, the study was published with no mention of any of those problems, or the FDA’s determination.

“The FDA has legal as well as ethical responsibilities regarding the scientific misconduct it finds during its inspections. When the agency withholds the identify 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,” Seife concluded. “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.”

Seife suggests that the FDA should make the information more readily available, and in unredacted form. He also called on the journals themselves to make more of an effort to ensure the integrity of the research published in their pages.

“Currently, there is no formal requirement for authors seeking to publish clinical trial data to disclose any adverse findings noted during FDA inspections,” Seife noted. “Journals should require that any such findings be disclosed.”