Taams A C, Herberts C A, Egberts A C G, Zafiropoulos N, Pignatti F, Bloem L T
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
ESMO Open. 2024 Dec;9(12):103991. doi: 10.1016/j.esmoop.2024.103991. Epub 2024 Dec 9.
Drug regulators assess and describe uncertainties regarding treatment outcomes and the benefit-risk balance of newly authorised medicines. We aimed to evaluate the type and number of uncertainties described in the benefit-risk assessment for initial marketing authorisations of oncology medicines assessed by the European Medicines Agency (EMA). We also aimed to develop a systematic classification of uncertainties to contribute to improved communication about uncertainties.
We included all medicines containing a new active substance assessed by the EMA and granted an initial marketing authorisation by the European Commission in 2011-2022 for an oncology indication. We extracted characteristics of these oncology medicines and uncertainties described under the benefit-risk balance section of European public assessment reports. Uncertainties were categorised and their frequencies stratified according to time of marketing authorisation, and medicine and regulatory characteristics.
In total, 121 oncology medicines were included for which 800 (median 6, range 0-23) uncertainties were identified. Uncertainties were classified into five categories: safety (n = 404, 51%), efficacy (n = 322, 40%), pharmacology (n = 58, 7%), use in clinical practice (n = 10, 1%), and quality (n = 6, 1%). Among 27 subcategories, most uncertainties were related to specific adverse events (n = 156, 20%), effect size (n = 155, 20%), safety in subpopulations (n = 124, 16%), or efficacy in subpopulations (n = 88, 11%). The type of medicine (P = 0.012), type of marketing authorisation (P = 0.001), and year of marketing authorisation (P = 0.007) were associated with the number of uncertainties per medicine, with the highest number observed for cell and gene therapies [8 (3-23)], medicines granted conditional marketing authorisation [7 (3-23)], and medicines authorised in 2019-2022 [7 (2-23)].
At the time of initial marketing authorisation of oncology medicines, uncertainties about their benefit-risk balance most often concerned safety aspects, followed by efficacy. The number of uncertainties was highest for cell and gene therapies, conditionally authorised medicines, and medicines authorised in recent years.
药品监管机构评估并描述有关治疗结果以及新获批药品的获益-风险平衡的不确定性。我们旨在评估欧洲药品管理局（EMA）评估的肿瘤学药品初始上市许可的获益-风险评估中所描述的不确定性的类型和数量。我们还旨在制定不确定性的系统分类，以促进有关不确定性的沟通改善。
我们纳入了所有含有新活性物质且在2011年至2022年期间由EMA评估并获欧盟委员会初始上市许可用于肿瘤学适应症的药品。我们提取了这些肿瘤学药品的特征以及欧洲公共评估报告的获益-风险平衡部分所描述的不确定性。根据上市许可时间、药品和监管特征对不确定性进行分类并对其频率进行分层。
总共纳入了121种肿瘤学药品，确定了800个（中位数为6，范围为0至23）不确定性。不确定性分为五类：安全性（n = 404，51%）、有效性（n = 322，40%）、药理学（n = 58，7%）、临床实践中的使用（n = 10，1%）和质量（n = 6，1%）。在27个子类别中，大多数不确定性与特定不良事件（n = 156，20%）、效应大小（n = 155，20%）、亚组安全性（n = 124，16%）或亚组有效性（n = 88，11%）有关。药品类型（P = 0.012）、上市许可类型（P = 0.001）和上市许可年份（P = 0.007）与每种药品的不确定性数量相关，细胞和基因疗法[8（3至23）]、获得有条件上市许可的药品[7（3至23）]以及2019年至2022年获批的药品[7（2至23）]的不确定性数量最高。
在肿瘤学药品初始上市许可时，其获益-风险平衡的不确定性最常涉及安全性方面，其次是有效性。细胞和基因疗法、有条件获批的药品以及近年来获批的药品的不确定性数量最高。
