Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines
Defining Efficacy Estimands in Clinical Trials: Examples Illustrating ICH E9(R1) Guidelines
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DOI：
10.1007/s43441-019-00065-7
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发表时间：
2020-03-01
影响因子：
1.5
通讯作者：
O'Kelly, Michael
中科院分区：
文献类型：
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作者：
Ratitch, Bohdana;Goel, Niti;O'Kelly, Michael
本文提供了遵循 ICH E9(R1) 指南在现实场景中定义估计值的示例。关于选择估计量和估计量的详细讨论可以在我们的配套论文中找到。说明了复杂性不断增加的三种情况。第一个例子是重度抑郁症的概念验证试验，其中选择被评估者来支持申办者是否继续开发的决定。第二个和第三个例子分别是严重哮喘和类风湿关节炎的验证性试验。我们讨论每次试验期间预期的并发事件以及如何处理这些事件，以便与研究目标保持一致。这些示例中讨论的估计值并不是其各自场景的唯一可接受的选择。目的是说明关键概念，而不是关注特定选择。重点是遵循研究开发过程，其中估计值以连贯的方式将研究目标与数据收集和分析联系起来，从而避免目标、估计值和分析之间的脱节。
This paper provides examples of defining estimands in real-world scenarios following ICH E9(R1) guidelines. Detailed discussions on choosing the estimands and estimators can be found in our companion papers. Three scenarios of increasing complexity are illustrated. The first example is a proof-of-concept trial in major depressive disorder where the estimand is chosen to support the sponsor decision on whether to continue development. The second and third examples are confirmatory trials in severe asthma and rheumatoid arthritis respectively. We discuss the intercurrent events expected during each trial and how they can be handled so as to be consistent with the study objectives. The estimands discussed in these examples are not the only acceptable choices for their respective scenarios. The intent is to illustrate the key concepts rather than focus on specific choices. Emphasis is placed on following a study development process where estimands link the study objectives with data collection and analysis in a coherent manner, thereby avoiding disconnect between objectives, estimands, and analyses.