Gräf Débora D, Westphal Lukas, Kimmelman Jonathan, Hallgreen Christine E
Department of Pharmacy, Copenhagen Centre for Regulatory Science, University of Copenhagen, Copenhagen, Denmark.
Department of Equity, Ethics and Policy, McGill University, Montreal, Québec, Canada.
Clin Pharmacol Ther. 2025 Aug;118(2):459-469. doi: 10.1002/cpt.3694. Epub 2025 May 5.
Therapeutic and prophylactic agents require robust evidence before patient use. Randomized controlled trials are essential for evaluating safety and efficacy but often exclude specific populations that are also targets for the intervention. This study assessed which populations are included in vaccine registration studies and/or addressed in label indications, and if special populations are considered at any point in the regulatory life cycle of vaccines approved in the European Union. We analyzed product labels, pivotal studies, risk management plans, and post-authorization studies for all vaccines centrally approved via the European Medicines Agency between 2012 and 2022. For the 31 vaccines approved, we identified 90 pivotal studies supporting initial marketing authorizations and 46 studies supporting product revisions. At the end of our follow-up, 27 vaccines (87%) were approved for adults, 19 (68%) for pediatric patients, 3 (11%) were recommended for pregnant populations, 4 (14%) for breastfeeding populations, and 7 (23%) for immunocompromised populations. Pregnant, breastfeeding, and immunocompromised individuals were rarely included in studies supporting regulatory actions. We observed a slight increase in the inclusion of special populations in post-marketing studies, yet this had limited impact on product indications or information availability on labels. Pivotal studies supporting vaccine registrations were also highly selective and predominantly conducted in high-income settings. These findings highlight significant variations in how different populations are considered during vaccine development and by regulators. Greater inclusion of special populations in the evidence-generation chain is essential to ensure that vaccines respond to unmet medical needs equitably.
治疗性和预防性药物在用于患者之前需要有力的证据。随机对照试验对于评估安全性和有效性至关重要,但通常会排除也是干预目标的特定人群。本研究评估了疫苗注册研究中纳入了哪些人群和/或标签适应症中涉及了哪些人群,以及在欧盟批准的疫苗监管生命周期的任何阶段是否考虑了特殊人群。我们分析了2012年至2022年期间通过欧洲药品管理局集中批准的所有疫苗的产品标签、关键研究、风险管理计划和上市后研究。对于批准的31种疫苗,我们确定了90项支持初始上市许可的关键研究和46项支持产品修订的研究。在我们随访结束时,27种疫苗(87%)被批准用于成人,19种(68%)用于儿科患者,3种(11%)被推荐用于孕妇群体,4种(14%)用于哺乳期群体,7种(23%)用于免疫功能低下群体。支持监管行动的研究很少纳入孕妇、哺乳期妇女和免疫功能低下的个体。我们观察到上市后研究中特殊人群的纳入略有增加,但这对产品适应症或标签上的信息可用性影响有限。支持疫苗注册的关键研究也具有高度选择性,主要在高收入环境中进行。这些发现凸显了在疫苗研发过程中以及监管机构对不同人群的考虑方式存在显著差异。在证据生成链中更多地纳入特殊人群对于确保疫苗公平地满足未满足的医疗需求至关重要。