Estimand framework: Delineating what to be estimated with clinical questions of interest in clinical trials
Estimand framework: Delineating what to be estimated with clinical questions of interest in clinical trials
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DOI：
10.1016/j.cct.2020.106093
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发表时间：
2020-09-01
影响因子：
2.2
通讯作者：
Liu, Guanghan
中科院分区：
文献类型：
--
作者：
Jin, Man;Liu, Guanghan
ICH（国际协调委员会）E9 R1（2019）提出了一个框架来定义临床试验中的估算。尽管在美国食品和药物管理局（FDA）发布关于处理临床试验中缺失数据的专家组报告时就提出了评估的概念，但直到最近的ICH E9 （R1）附录才制定了包括属性和不同策略在内的许多细节。一个明确定义的评估应该考虑五个属性，包括患者群体、感兴趣的治疗方案、终点/变量、并发事件（IEs）的处理和评估治疗效果的总结措施。为了评估一种新的研究药物或生物制品的潜在治疗效果，最好考虑与研究目标一致的估计，并考虑对利益相关者（如医生或患者、卫生当局管理部门和付款人等）有意义的估计。本文将回顾评估框架的概念、属性和策略，并以临床试验实例加以说明。在纵向临床试验的因果推理框架内讨论了一些常见的估计及其相关的科学问题。
ICH (International Council for Harmonization) E9 R1 (2019) proposes a framework to define estimands in clinical trials. Although the concept of estimand was proposed previously when US Food and Drug Administration (FDA) issued the panel report on handling missing data in clinical trials, many details including attributes and different strategies have not been developed until the recent ICH E9 (R1) addendum. A clearly defined estimand should include considerations of five attributes including patient population, treatment regimen of interest, endpoint/variables, handling of intercurrent events (IEs), and summary measures for assessing treatment effect. To evaluate the underlying treatment effects of a new investigational drug or biologic product, it is desirable to consider estimands that are aligned with the objectives of the study and that are meaningful to the stakeholders such as physicians or patients, health authority administration, and payers, etc.. In this paper, the concepts, attributes and strategies of the estimand framework will be reviewed and illustrated with clinical trial examples. Some common estimands and their associated scientific questions are discussed within a causal inference framework for longitudinal clinical trials.