Objective To characterize potential drug safety signals identified from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), from 2008 to 2019, to determine how often these signals resulted in regulatory action by the FDA and whether these actions were corroborated by published research findings or public assessments by the Sentinel Initiative. Design Cross sectional study. Setting USA. Population Safety signals identified from the FAERS and publicly reported by the FDA between 2008 and 2019; and review of the relevant literature published before and after safety signals were reported in 2014-15. Literature searches were performed in November 2019, Sentinel Initiative assessments were searched in December 2021, and data analysis was finalized in December 2021. Main outcome measures Safety signals and resulting regulatory actions; number and characteristics of published studies, including corroboration of regulatory action as evidenced by significant associations (or no associations) between the drug related to the signal and the adverse event. Results From 2008 to 2019, 603 potential safety signals identified from the FAERS were reported by the FDA (median 48 annually, interquartile range 41-61), of which 413 (68.5%) were resolved as of December 2021 (372 of 399 (93.2%) signals ≥3 years old were resolved). Among the resolved safety signals, 91 (22.0%) led to no regulatory action and 322 (78.0%) resulted in regulatory action, including 319 (77.2%) changes to drug labeling and 59 (14.3%) drug safety communications or other public communications from the FDA. For a subset of 82 potential safety signals reported in 2014-15, a literature search identified 1712 relevant publications; 1201 (70.2%) were case reports or case series. Among these 82 safety signals, 76 (92.7%) were resolved, of which relevant published research was identified for 57 (75.0%) signals and relevant Sentinel Initiative assessments for four (5.3%) signals. Regulatory actions by the FDA were corroborated by at least one relevant published research study for 17 of the 57 (29.8%) resolved safety signals; none of the relevant Sentinel Initiative assessments corroborated FDA regulatory action. Conclusions Most potential safety signals identified from the FAERS led to regulatory action by the FDA. Only a third of regulatory actions were corroborated by published research, however, and none by public assessments from the Sentinel Initiative. These findings suggest that either the FDA is taking regulatory actions based on evidence not made publicly available or more comprehensive safety evaluations might be needed when potential safety signals are identified. The dataset will be made available via a publicly accessible repository on publication.

中文翻译：

---

美国食品和药物管理局不良事件报告系统确定的安全信号的特征和确证，2008-19：横断面研究

目的 描述 2008 年至 2019 年美国食品和药物管理局 (FDA) 不良事件报告系统 (FAERS) 确定的潜在药物安全信号的特征，以确定这些信号导致 FDA 采取监管行动的频率以及这些行动是否得到证实通过 Sentinel Initiative 发表的研究结果或公共评估。设计横断面研究。设置美国。2008 年至 2019 年期间从 FAERS 确定并由 FDA 公开报告的人口安全信号；并回顾了 2014-15 年报告安全信号之前和之后发表的相关文献。2019 年 11 月进行了文献检索，2021 年 12 月检索了 Sentinel Initiative 评估，2021 年 12 月完成了数据分析。主要成果措施 安全信号和由此产生的监管行动；已发表研究的数量和特征，包括通过与信号相关的药物与不良事件之间的显着关联（或无关联）证明监管行动的证实。结果 从 2008 年到 2019 年，FDA 报告了 603 个从 FAERS 识别出的潜在安全信号（每年中位数 48 个，四分位数范围 41-61），截至 2021 年 12 月，其中 413 个（68.5%）得到解决（399 个中的 372 个（93.2 个） % ≥ 3 岁的信号得到解决）。在已解决的安全信号中，91 个 (22.0%) 没有导致监管行动，322 个 (78.0%) 导致监管行动，包括 319 个 (77.2%) 药品标签变更和 59 个 (14.3%) 药品安全通讯或其他公共通讯来自美国食品和药物管理局。对于 2014-15 年报告的 82 个潜在安全信号的子集，文献检索确定了 1712 份相关出版物；1201 (70.2%) 是病例报告或病例系列。在这 82 个安全信号中，76 个 (92.7%) 得到解决，其中 57 个 (75.0%) 信号的相关已发表研究被确定，4 个 (5.3%) 信号的相关前哨倡议评估被确定。FDA 的监管行动得到了至少一项已发表的相关研究的证实，该研究证实了 57 个已解决的安全信号中的 17 个（29.8%）；相关的 Sentinel Initiative 评估均未证实 FDA 的监管行动。结论 FAERS 确定的大多数潜在安全信号导致 FDA 采取监管行动。然而，只有三分之一的监管行动得到了已发表研究的证实，Sentinel Initiative 的公共评估也没有。这些发现表明，要么 FDA 正在根据未公开的证据采取监管行动，要么在确定潜在的安全信号时可能需要进行更全面的安全评估。该数据集将在发布时通过可公开访问的存储库提供。