Eli Lilly, Montreal, Quebec, Canada.
Kezar Life Sciences, South San Francisco, CA, USA.
Ther Innov Regul Sci. 2020 Mar;54(2):370-384. doi: 10.1007/s43441-019-00065-7. Epub 2020 Jan 6.
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.
本文提供了遵循 ICH E9(R1) 指南在真实场景中定义目标值的示例。关于选择目标值和估计量的详细讨论可以在我们的配套论文中找到。本文说明了三个复杂程度递增的场景。第一个示例是重度抑郁症中的概念验证试验，其中选择目标值是为了支持赞助商关于是否继续开发的决策。第二和第三个示例分别是在严重哮喘和类风湿关节炎中的确证性试验。我们讨论了每个试验中预期的并发事件，以及如何处理这些事件，以使其与研究目标保持一致。本文讨论的目标值并不是各自场景中唯一可接受的选择。本文的目的是说明关键概念，而不是专注于特定的选择。重点是遵循研究开发过程，其中目标值将研究目标与数据收集和分析以连贯的方式联系起来，从而避免目标、目标值和分析之间的脱节。
