Department of Health Policy, London School of Economics and Political Science, London, UK.
Austrian National Public Health Institute (Gesundheit Österreich GmbH/GÖG), Vienna, Austria.
Clin Pharmacol Ther. 2022 Oct;112(4):846-852. doi: 10.1002/cpt.2679. Epub 2022 Jun 23.
To address unresolved questions about drug safety and efficacy at the time of approval, the European Medicines Agency (EMA) may require that manufacturers conduct additional studies during the postmarketing period. As a growing proportion of new cancer drugs are approved on the basis of limited evidence of clinical benefit, timely completion of postmarketing requirements is important. We used publicly available regulatory documents to evaluate key characteristics of pivotal studies supporting EMA-approved cancer drugs from 2004-2014 and assessed completion rates of postmarketing data collection requirements after a minimum of 5 years. From 2004-2014, 79% (45/57) of EMA-approved cancer drugs had to fulfill postmarketing requirements. Pivotal trials supporting the approval of cancer drugs with postmarketing requirements were less likely to have randomized designs (41/61, 67% vs. 11/11, 100%), include an active comparator (20/61, 33% vs. 10/11, 91%), or measure overall survival as the primary study end point (18/61, 30% vs. 6/11, 55%) compared with pivotal trials for drugs without postmarketing requirements. Among 200 postmarketing requirements, almost half were designed to assess drug safety. After a minimum of 5 years, 60% (121/200) of requirements were completed, 10% (19/200) were ongoing, and 30% (60/200) were delayed. About half (40/75, 53%) of postmarketing requirements for new clinical studies were completed on time. Delays in the completion of postmarketing requirements often did not impact the likelihood of drugs receiving permanent marketing authorization (87%, 39/45) after 5 years. Our findings highlight the need for EMA to better enforce its authority to require timely completion of postmarketing requirements and studies.
为了解决药物批准时仍存在的安全性和疗效方面的未决问题，欧洲药品管理局（EMA）可能会要求制造商在上市后期间进行额外的研究。随着越来越多的新癌症药物在临床获益证据有限的基础上获得批准，及时完成上市后要求非常重要。我们使用公开的监管文件评估了 2004 年至 2014 年期间支持 EMA 批准的癌症药物的关键研究的主要特征，并评估了至少 5 年后完成上市后数据收集要求的完成率。2004 年至 2014 年，79%（45/57）的 EMA 批准的癌症药物必须满足上市后要求。支持有上市后要求的癌症药物批准的关键性试验不太可能采用随机设计（41/61，67%比 11/11，100%），包括活性对照（20/61，33%比 10/11，91%），或测量总生存期作为主要研究终点（18/61，30%比 6/11，55%）与没有上市后要求的药物的关键性试验相比。在 200 项上市后要求中，近一半是为了评估药物安全性而设计的。至少 5 年后，完成了 60%（121/200）的要求，10%（19/200）正在进行中，30%（60/200）延迟。大约一半（40/75，53%）的新临床研究的上市后要求按时完成。上市后要求完成的延迟通常不会影响药物在 5 年后获得永久上市授权的可能性（87%，39/45）。我们的研究结果强调了 EMA 加强其要求及时完成上市后要求和研究的权力的必要性。
