Time-to-event estimands are central to many oncology clinical trials. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest and requires predefining the handling of intercurrent events that occur after treatment initiation and either preclude the observation of an event of interest or impact the interpretation of the treatment effect. We discuss a practical problem in clinical trial design and execution, i.e. in some clinical contexts it is not feasible to systematically follow patients to an event of interest. Loss to follow-up in the presence of intercurrent events can affect the meaning and interpretation of the study results. We provide recommendations for trial design, stressing the need for close alignment of the clinical question of interest and study design, impact on data collection and other practical implications. When patients cannot be systematically followed, compromise may be necessary to select the best available estimand that can be feasibly estimated under the circumstances. We discuss the use of sensitivity and supplementary analyses to examine assumptions of interest.

翻译：时间至事件治疗效应估计是众多肿瘤学临床试验的核心要素。估计框架（ICH E9指南增补）要求精确定义目标治疗效应以匹配临床问题，并预先规定对治疗启动后发生且会阻碍目标事件观察或影响治疗效应解读的伴随事件的处理策略。本文探讨临床试验设计与执行中的一个实际问题——即在某些临床背景下无法系统追踪患者直至目标事件发生。伴随事件背景下的失访现象可能影响研究结果的意义与解读。我们提出试验设计建议，强调目标临床问题与研究设计的紧密契合、对数据采集的影响及其他实际意义。当无法系统追踪患者时，可能需要权衡取舍以选择在现有条件下可实际估计的最佳可用估计量。本文还讨论了如何通过敏感性分析和补充分析来检验相关假设。