For the analysis of a time-to-event endpoint in a single-arm or randomized clinical trial it is generally perceived that interpretation of a given estimate of the survival function, or the comparison between two groups, hinges on some quantification of the amount of follow-up. Typically, a median of some loosely defined quantity is reported. However, whatever median is reported, is typically not answering the question(s) trialists actually have in terms of follow-up quantification. In this paper, inspired by the estimand framework, we formulate a comprehensive list of relevant scientific questions that trialists have when reporting time-to-event data. We illustrate how these questions should be answered, and that reference to an unclearly defined follow-up quantity is not needed at all. In drug development, key decisions are made based on randomized controlled trials, and we therefore also discuss relevant scientific questions not only when looking at a time-to-event endpoint in one group, but also for comparisons. We find that with the advent of new therapies, patterns of survival functions in trials emerge, e.g. delayed separation in RCTs or the potential for cure, that may require different thinking on some of the relevant scientific questions around follow-up. We conclude the paper with practical recommendations.
翻译:分析单臂或随机临床试验的时间到时间端点分析一般认为,对生存功能特定估计的解释,或两个组之间的比较,取决于对后续行动数量的某种量化。通常报告数量中位数,有些定义松散。然而,无论报告中位数,一般都没有回答试验人员实际上在后续量化方面所遇到的问题。在估计框架的启发下,本文件列出了试验人员在报告时间到活动数据时所了解的有关科学问题的综合清单。我们说明了这些问题应如何回答,根本不需要提及定义不明确的后续数量。在药物开发中,关键决定是根据随机控制的试验作出的,因此我们不仅在研究一个组的时间到活动终点时,而且还讨论有关的科学问题。我们发现,随着新疗法的出现,试验中的生存功能模式出现,例如,在RCT的延迟分离或实际的治疗潜力,我们可能需要对一些科学问题进行不同的思考。我们可能需要对相关文件进行不同的思考。