Essink Sharon C M, Zomerdijk Inge M, Goedecke Thomas, Straus Sabine M J M, Gardarsdottir Helga, De Bruin Marie L
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Department of Pharmacovigilance, Medicines Evaluation Board, Utrecht, The Netherlands.
Clin Pharmacol Ther. 2025 Apr;117(4):1106-1114. doi: 10.1002/cpt.3569. Epub 2025 Jan 24.
Insights into the time needed for evaluation of risk minimization measures' (RMMs) effectiveness might identify areas for improvement. We assessed the duration of time intervals between regulatory milestones for RMM effectiveness studies assessed by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA). We included completed RMM effectiveness post-authorization safety studies (PASSs) assessed by PRAC between 2016 and 2022. Regulatory documents submitted by marketing authorization holders and assessment reports were extracted from non-public EMA databases. To calculate the duration of time intervals, we collected the dates of study request, protocol assessment start, protocol approval, study start, final study report assessment start, and final study report PRAC outcome. We identified 98 PASSs. The median duration from study request to final study report PRAC outcome was 52 months (Q1-Q3: 40-70). The median duration from study request to study start was 21 months (Q1-Q3: 15-30; n = 95) and from study start to final study report assessment start was 21 months (Q1-Q3: 13-36; n = 95). The final study report assessment often comprised <6 months (median: 4; Q1-Q3: 1-6). For PASSs with a PRAC-approved protocol (n = 80, 81.6%), the median duration of protocol assessment was 7 months (Q1-Q3: 4-10). Concluding, the median duration from study request to RMM effectiveness PASS completion exceeded 4 years. Next to the study conduct duration, the period from study request until study start was the most time-consuming. The duration of this period might be minimized by improved guidance on RMM effectiveness PASSs and encouraging timely protocol submission.
深入了解评估风险最小化措施（RMM）有效性所需的时间，可能会发现改进的领域。我们评估了欧洲药品管理局（EMA）的药物警戒风险评估委员会（PRAC）评估的RMM有效性研究的监管里程碑之间的时间间隔。我们纳入了2016年至2022年间PRAC评估的已完成的RMM有效性上市后安全性研究（PASS）。从EMA非公开数据库中提取了上市许可持有人提交的监管文件和评估报告。为了计算时间间隔的时长，我们收集了研究申请日期、方案评估开始日期、方案批准日期、研究开始日期、最终研究报告评估开始日期以及最终研究报告PRAC结果日期。我们确定了98项PASS。从研究申请到最终研究报告PRAC结果的中位时长为52个月（第一四分位数-第三四分位数：40-70）。从研究申请到研究开始的中位时长为21个月（第一四分位数-第三四分位数：15-30；n = 95），从研究开始到最终研究报告评估开始的中位时长为21个月（第一四分位数-第三四分位数：13-36；n = 95）。最终研究报告评估通常持续不到6个月（中位值：4；第一四分位数-第三四分位数：1-6）。对于PRAC批准方案的PASS（n = 80，81.6%），方案评估的中位时长为7个月（第一四分位数-第三四分位数：4-10）。总之，从研究申请到RMM有效性PASS完成的中位时长超过4年。除了研究开展时长外，从研究申请到研究开始的这段时间是最耗时的。通过改进RMM有效性PASS的指南并鼓励及时提交方案，这段时间的时长可能会缩短。
