标题： 估计量框架和生存时间结果临床试验中的事件处理 显示英文标题

标题： Estimand framework and intercurrent events handling for clinical trials with time-to-event outcomes

摘要： ICH E9(R1)指南提出了临床试验的估计量框架，提出了处理同时发生事件（ICEs）的五种策略，并对定量结果和分类结果进行了全面的讨论和许多实际临床案例。 然而，在ICH E9(R1)中，对于时间至事件（TTE）结果的讨论是缺乏的。 在本文中，我们讨论如何为具有TTE结果的临床试验定义估计量以及如何处理ICEs。 具体而言，我们讨论了六种处理ICE的策略，包括ICH E9(R1)提出的五种策略和一种新的策略，即竞争风险策略。 与ICH E9(R1)相比，本文的创新之处有三方面：(1) 估计量是根据潜在结果来定义的，(2) 方法可以直接利用时间依赖性协变量，(3) 相应地讨论了高效的估计量。 显示英文摘要

摘要： The ICH E9(R1) guideline presents a framework of estimand for clinical trials, proposes five strategies for handling intercurrent events (ICEs), and provides a comprehensive discussion and many real-life clinical examples for quantitative outcomes and categorical outcomes. However, in ICH E9(R1) the discussion is lacking for time-to-event (TTE) outcomes. In this paper, we discuss how to define estimands and how to handle ICEs for clinical trials with TTE outcomes. Specifically, we discuss six ICE handling strategies, including those five strategies proposed by ICH E9(R1) and a new strategy, the competing-risk strategy. Compared with ICH E9(R1), the novelty of this paper is three-fold: (1) the estimands are defined in terms of potential outcomes, (2) the methods can utilize time-dependent covariates straightforwardly, and (3) the efficient estimators are discussed accordingly.