英国牛津大学Ben Goldacre课题组的一项最新研究对ClinicalTrials.gov上报告临床试验结果是否符合法律要求进行了分析。2020年1月17日出版的《柳叶刀》发表了这项成果。

未能报告临床试验的结果可能会使临床实践的证据基础失真，违背研究人员对参与者的伦理义务，且造成研究浪费。2007年食品和药品管理局修正法案（FDAAA）要求适用试验的赞助人在完成后的1年内将结果直接上报至ClinicalTrials.gov。

2008年3月至2019年9月，研究组每月从ClinicalTrials.gov上下载所有注册试验的数据，并进行横断面分析。研究队列包括符合FDAAA的所有适用试验，对FDAAA2007最终规则的依从性进行了分析。

共有4209项试验应当报告结果，其中1722项（40.9%）在1年期限内提交，共有2686项（63.8%）提交了结果。自2018年7月以来，依从性未明显改善。企业赞助人比非企业、非美国政府赞助人的依从性更高，优势比为3.08；进行大量试验的赞助人比规模较小的赞助人的依从性更高，优势比为11.84。试验结束至提交数据的中位时间为424天，比FDAAA要求的1年多了59天。

研究结果表明，赞助人对FDAAA2007的依从性较差，且无改善。这是第一次全面评估FDAAA2007最终规则依从性的研究，部分反映了监管机构缺乏执行力。赞助人的有效执行和行动有待加强，对每个赞助人的依从性进行公开审查可能会有所帮助。 

附：英文原文

Title: Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study

Author: Nicholas J DeVito, Seb Bacon, Ben Goldacre

Issue&Volume: January 17, 2020

Abstract:

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.

DOI: 10.1016/S0140-6736(19)33220-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33220-9/fulltext