Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study
Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study
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DOI：
10.1016/s0140-6736(19)33220-9
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发表时间：
2020-02-01
期刊：
影响因子：
168.9
通讯作者：
Goldacre, Ben
中科院分区：
文献类型：
--
作者：
DeVito, Nicholas J.;Bacon, Seb;Goldacre, Ben
不报告临床试验结果会扭曲临床实践的证据基础，违反研究人员对参与者的道德义务，并且是研究浪费的一个重要来源。2007年的食品和药物管理局修正案（FDAAA）现在要求适用试验的发起人在完成后一年内直接向ClinicalTrials.gov报告其结果。该法案最终规则涵盖的首批试验将于2018年1月报告结果。在这项队列研究中，我们开始评估依从性。方法2018年3月至2019年9月，我们每月在ClinicalTrials.gov上下载所有注册试验的数据。本文中所有横断面分析的数据均取自2019年9月16日的ClinicalTrials.gov；月度趋势分析使用了2018年3月至2019年9月每个月最接近15日的存档数据。我们的研究队列包括所有根据FDAAA报告结果的适用试验。我们排除了所有不适用的试验，那些尚未报告的试验，以及那些给予了允许延迟报告的证书的试验。如果试验结果已经提交，并且可以公开获得，或者正在ClinicalTrials.gov上进行质量控制审查，则该试验被视为已报告。如果这些结果是在主要完成日期的一年内提交的，则该试验被认为是符合法律要求的。我们描述了对FDAAA 2007年最终规则的遵守情况，使用逻辑回归模型评估了与结果报告相关的试验特征，描述了申办者水平报告，检查了报告趋势，并使用Kaplan-Meier方法描述了报告时间。报告结果为4209项试验；1722例（40.9%;95% CI 39.4-42.2）在1年期限内完成。2686（63.8%; 62.4 -65.3）项试验在任何时候都提交了结果。自2018年7月以来，合规情况没有改善。行业赞助者比非行业、非美国政府赞助者更容易依从（比值比[OR] 3.08 [95% CI 2.52-3.77]），进行大量试验的赞助者比小规模的赞助者更容易依从（比值比[OR] 11.84[9.36-14.99]）。从主要完成日期到提交日期的中位延迟为424天（95% CI 412-435），比1年的法定报告要求高出59天。对2007年FDAAA的遵守情况很差，而且没有改善。据我们所知，这是第一个全面评估符合2007年FDAAA最终规则的研究。合规不力可能反映出监管机构执法不力。需要发起人的有效执法和行动；在此之前，对每个保荐人的合规情况进行公开审计可能会有所帮助。我们将在fdaaa.trialstracker.net上维护每个个体赞助商和试验的最新合规数据。爱思唯尔版权所有版权所有。
Background Failure to report the results of a clinical trial can distort the evidence base for clinical practice, breaches researchers' ethical obligations to participants, and represents an important source of research waste. The Food and Drug Administration Amendments Act (FDAAA) of 2007 now requires sponsors of applicable trials to report their results directly onto ClinicalTrials.gov within 1 year of completion. The first trials covered by the Final Rule of this act became due to report results in January, 2018. In this cohort study, we set out to assess compliance.Methods We downloaded data for all registered trials on ClinicalTrials.gov each month from March, 2018, to September, 2019. All cross-sectional analyses in this manuscript were performed on data extracted from ClinicalTrials.gov on Sept 16, 2019; monthly trends analysis used archived data closest to the 15th day of each month from March, 2018, to September, 2019. Our study cohort included all applicable trials due to report results under FDAAA. We excluded all non-applicable trials, those not yet due to report, and those given a certificate allowing for delayed reporting. A trial was considered reported if results had been submitted and were either publicly available, or undergoing quality control review at ClinicalTrials.gov. A trial was considered compliant if these results were submitted within 1 year of the primary completion date, as required by the legislation. We described compliance with the FDAAA 2007 Final Rule, assessed trial characteristics associated with results reporting using logistic regression models, described sponsor-level reporting, examined trends in reporting, and described time-to-report using the Kaplan-Meier method.Findings 4209 trials were due to report results; 1722 (40.9%; 95% CI 39.4-42.2) did so within the 1-year deadline. 2686 (63.8%; 62 .4-65.3) trials had results submitted at any time. Compliance has not improved since July, 2018. Industry sponsors were significantly more likely to be compliant than non-industry, non-US Government sponsors (odds ratio [OR] 3.08 [95% CI 2.52-3.77]), and sponsors running large numbers of trials were significantly more likely to be compliant than smaller sponsors (OR 11.84 [9.36-14.99]). The median delay from primary completion date to submission date was 424 days (95% CI 412-435), 59 days higher than the legal reporting requirement of 1 year.Interpretation Compliance with the FDAAA 2007 is poor, and not improving. To our knowledge, this is the first study to fully assess compliance with the Final Rule of the FDAAA 2007. Poor compliance is likely to reflect lack of enforcement by regulators. Effective enforcement and action from sponsors is needed; until then, open public audit of compliance for each individual sponsor may help. We will maintain updated compliance data for each individual sponsor and trial at fdaaa.trialstracker.net. Copyright (C) 2020 Elsevier Ltd. All rights reserved.