Research Misconduct Identified by the US Food and Drug Administration Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature
Research Misconduct Identified by the US Food and Drug Administration Out of Sight, Out of Mind, Out of the Peer-Reviewed Literature
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DOI：
10.1001/jamainternmed.2014.7774
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发表时间：
2015-04-01
影响因子：
39
通讯作者：
Seife, Charles
中科院分区：
文献类型：
--
作者：
Seife, Charles
重要的是，美国食品和药物管理局(FDA)每年都会检查数百个对人类参与者进行生物医学研究的临床地点，偶尔会发现大量偏离良好临床实践和研究不当行为的证据。然而，FDA没有系统的方法将这些发现传达给科学界，留下了由政府机构检测到的研究不当行为在同行审查文献中未被提及的可能性。目的识别已发表的临床试验，其中FDA检查发现了令人反感的条件或做法的重要证据，描述违规行为，并确定这些违规行为是否在同行审查文献中提到。设计并设置对公开可获得的文件的横断面分析，日期为1998年1月1日至2013年9月30日，描述FDA对发现不良条件或做法的重要证据的临床试验站点的检查。对于可能与特定已发表临床试验相关联的每个检查文件的主要结果和措施，主要测量是/否确定在同行评议文献中是否提及FDA已发现的问题。结果共确定57项已发表临床试验，FDA对试验站点的检查发现了以下一项或多项问题的重要证据：伪造或提交虚假信息，22项试验(39%)；不良事件报告问题，14次(25%)；违反规程，42次(74%)；记录不充分或不准确，35次(61%)；未能保护患者安全和/或监督或知情同意的问题，30次(53%)；以及未以其他方式分类的违规行为，20次(35%)。在FDA发现重大违规行为的78篇论文中，只有3篇(4%)提到了检查过程中发现的令人反感的条件或做法。随后没有发表任何更正、撤回、担忧表达或其他承认检查确定的关键问题的评论。结论和相关性当FDA发现与良好临床实践显著背离时，这些发现很少反映在同行评议的文献中，即使有证据表明数据造假或其他形式的研究不当行为。
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.