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.

翻译：ICH E9(R1)指南提出了临床试验的估计目标框架，提出了处理中间事件的五种策略，并对定量结局和分类结局进行了全面讨论并提供了许多现实临床案例。然而，ICH E9(R1)中缺乏对时间-事件结局的讨论。本文讨论了如何为具有时间-事件结局的临床试验定义估计目标以及如何处理中间事件。具体而言，我们讨论了六种中间事件处理策略，包括ICH E9(R1)提出的五种策略以及一种新策略——竞争风险策略。与ICH E9(R1)相比，本文的新颖性体现在三个方面：(1) 估计目标是根据潜在结局定义的；(2) 方法可以直接利用时间依赖性协变量；(3) 相应地讨论了高效估计量。