Research Misconduct Identified by the US Food and Drug Administration

Abstract

IMPORTANCE Every year, the US Food and Drug Administration (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, 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.OBJECTIVES 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. DESIGN AND SETTINGCross-sectional analysis of publicly available documents, dated from , describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. MAIN OUTCOMES AND MEASURESFor each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified. RESULTS Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 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%). 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. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.CONCLUSIONS AND RELEVANCE 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.

Blockchain protocols in clinical trials: Transparency and traceability of consent

“…The US Food and Drug Administration (FDA) reports some metrics that are related to the frequency of clinical investigator-related deficiencies, which show that almost 10% of trials they monitored suffer from consent collection issues, such as failure to re-consent when new information becomes available, use of expired forms or non-validated, unapproved forms, consent document not signed or not dated, missing pages in consent document provided to participants, failure to obtain written informed consent, parental permission obtained after child assent, changes made to the consent documents by hand and without IRB approval 3, 4 ( http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/UCM256376.pdf; http://www.yale.edu/hrpp/education/documents/CommonProblemsinInformedConsent_2013_vF.pptx). The study by Seife 5 analysed hundreds of clinical trial FDA inspection documents, covering the 1998–2013 period, and showed that a substantial number of them presented evidence of research misconduct, among which 53% were related to failure to protect the safety of patients and/or issues with oversight or informed consent.…”

What difference do retractions make? An estimate of the epistemic impact of retractions on recent meta-analyses

“…Further, it included meta-analyses of the same all very similar research question. Furthermore, the fabrication of data was uncovered exclusively in a single Chinese clinical site and, once all Chinese data was excluded, the trial yielded statistically significant positive results [16]. Therefore, the average distorting effect that retractions exert on the scientific literature remains to be assessed.…”

Contributions towards understanding and building sustainable science

“…This goes hand-in-hand with co-authors verifying results, but this is done by a researcher not directly affiliated with the research project. Auditing data is common practice in research that is subject to governmental oversight, for instance drug trials that are audited by the Food and Drug Administration (Seife 2015).…”