Research misconduct identified by the US Food and Drug Administration: Out of sight, out of mind, out of the peer-reviewed literature

Charles Seife

    Research output: Contribution to journalArticle

    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 SETTING: Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. MAIN OUTCOMES AND MEASURES: For 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.

    Original languageEnglish (US)
    Pages (from-to)567-577
    Number of pages11
    JournalJAMA Internal Medicine
    Volume175
    Issue number4
    DOIs
    StatePublished - Apr 1 2015

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    Scientific Misconduct
    United States Food and Drug Administration
    Clinical Trials
    Government Agencies
    Patient Safety
    Informed Consent
    Publications
    Biomedical Research
    Cross-Sectional Studies

    ASJC Scopus subject areas

    • Internal Medicine
    • Medicine(all)

    Cite this

    Research misconduct identified by the US Food and Drug Administration : Out of sight, out of mind, out of the peer-reviewed literature. / Seife, Charles.

    In: JAMA Internal Medicine, Vol. 175, No. 4, 01.04.2015, p. 567-577.

    Research output: Contribution to journalArticle

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    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 SETTING: Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. MAIN OUTCOMES AND MEASURES: For 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.",
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