Background/AimsSince the onset of the coronavirus disease 2019 (COVID-19) pandemic, 103.4 million cases and 1.1 million deaths have occurred nationally as of November 2023. Despite the benefit of mitigating measures, the pandemic’s effect on participant safety is rarely documented.MethodsThis study assessed noncompliance occurring from July 2019 to August 2021 that were stratified by the date of noncompliance (before or after restrictions). Events were described by size, site, noncompliance type, primary category, subcategory, and cause. In addition, noncompliance associated with COVID-19 was analyzed to determine characteristics.ResultsIn total, 323 noncompliance events occurred across 21,146 participants at risk in 35 protocols. The overall rate of noncompliance increased from 0.008 events per participant to 0.022 events per participant after the COVID-19 restrictions ( p < 0.001). For onsite protocols, the median within protocol change in rates was 0.001 (interquartile range = 0.141) after the onset of COVID-19 restrictions ( p = 0.54). For large-sized protocols ( n ≥ 100), the median within protocol change in rates was also 0.001 (interquartile range = 0.017) after COVID-19 restrictions ( p = 0.15). For events related to COVID-19 restrictions, 160/162 (99%) were minor deviations, 161/162 (99%) were procedural noncompliance, and 124/162 (77%) were an incomplete study visit.ConclusionThese noncompliance events have implications for clinical trial methodology because nonadherence to trial design can lead to participant safety concerns and loss of trial data validity. Protocols should be written to better facilitate the capture of all safety and efficacy data. This recommendation should be considered when changes occur to the protocol environment that are outside of the study team’s control.

中文翻译：

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重新思考临床研究方案：从 COVID-19 大流行中汲取的经验教训以及减少违规行为的建议

背景/目标自 2019 年冠状病毒病 (COVID-19) 大流行爆发以来，截至 2023 年 11 月，全国已发生 1.034 亿例病例和 110 万人死亡。尽管有缓解措施的好处，但该流行病对参与者安全的影响很少有记录。方法这研究评估了 2019 年 7 月至 2021 年 8 月发生的不合规情况，并按不合规日期（限制之前或之后）进行分层。事件按规模、地点、违规类型、主要类别、子类别和原因进行描述。此外，还分析了与 COVID-19 相关的不合规事件，以确定其特征。结果 35 个方案中，21,146 名面临风险的参与者总共发生了 323 起不合规事件。在实施 COVID-19 限制后，总体不合规率从每位参与者 0.008 起事件增加到每位参与者 0.022 起事件 (p < 0.001)。对于现场协议，在 COVID-19 限制开始后，协议变化率的中位数为 0.001（四分位数间距 = 0.141）（p = 0.54）。对于大型协议 ( n ≥ 100)，在 COVID-19 限制后，协议变化率的中位数也为 0.001（四分位数间距 = 0.017）（p = 0.15）。对于与 COVID-19 限制相关的事件，160/162 (99%) 为轻微偏差，161/162 (99%) 为程序不合规，124/162 (77%) 为不完整的研究访问。结论这些不合规事件具有影响对于临床试验方法，因为不遵守试验设计可能会导致参与者的安全问题和试验数据有效性的丧失。应编写协议以更好地促进所有安全性和有效性数据的捕获。当方案环境发生超出研究团队控制范围的变化时，应考虑此建议。