论文标题

在肿瘤学临床试验中的随访时间的量化,该试验有一个事件时间终点:提出正确的问题

Quantification of follow-up time in oncology clinical trials with a time-to-event endpoint: Asking the right questions

论文作者

Rufibach, Kaspar, Grinsted, Lynda, Li, Jiang, Weber, Hans-Jochen, Zheng, Cheng, Zhou, Jiangxiu

论文摘要

为了分析单臂或随机临床试验中事件端点的分析,通常认为对给定的生存函数估计值的解释或两组之间的比较,对随访量的某种量化进行了贴止。通常,报告了一些松散定义的数量的中位数。但是,无论报告中位数的任何中位数,通常都没有回答实际上在随访量化方面遇到的问题。在本文中,受估算和框架的启发,我们制定了一份全面的列表,这些列表在报告事件时间的数据时,试验者遇到的相关科学问题。我们说明了如何回答这些问题,根本不需要提及未明确定义的后续数量。在药物开发中,基于随机对照试验做出关键决策,因此,我们还讨论了相关的科学问题,不仅在查看一个组中的事件终点时,还讨论了比较。我们发现,需要对随访的一些相关科学问题的不同思考,具体取决于是否可以做出比例危害假设或预期生存功能的其他模式,例如延迟分离,越过生存功能或治愈的潜力。我们以实用的建议总结了本文。

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 different thinking about some of the relevant scientific questions around follow-up is required depending on whether a proportional hazards assumption can be made or other patterns of survival functions are anticipated, e.g. delayed separation, crossing survival functions, or the potential for cure. We conclude the paper with practical recommendations.

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