Estimand framework: Are we asking the right questions? A case study in the solid tumor setting
Estimand framework: Are we asking the right questions? A case study in the solid tumor setting
复制标题
评估框架：我们是否提出了正确的问题？实体瘤的病例研究
DOI：
10.1002/pst.2079
复制
发表时间：
2020-11-05
影响因子：
1.5
通讯作者：
George, Daniel
中科院分区：
文献类型：
--
作者：
Casey, Michelle;Degtyarev, Evgeny;George, Daniel
估计框架需要对感兴趣的临床问题（估计值）进行精确定义，因为随机化后“并发”事件的不同解释方式可能会导致不同的科学问题。后续治疗的开始在肿瘤学临床试验中很常见，如果此类治疗的开始发生在复发或进展事件之前，则被视为并发事件。在分析中解释这种并发事件的三种可能方法是在开始时进行审查，考虑在后续治疗开始之前和之后发生的复发或进展事件（包括死亡），或者将后续治疗的开始本身视为一个事件。新的估计框架澄清了这些分析解决了不同的问题（“如果没有患者接受后续治疗，药物是否会延迟复发？”与“无论是否接受后续治疗，药物是否会延迟复发？”与“药物是否会延迟复发或后续治疗的开始？”）。该框架有助于临床试验规划和设计期间的讨论，以确保感兴趣的关键问题、分析和解释之间的一致性。本文是跨行业合作的成果，旨在将国际协调委员会 E9 附录概念与应用联系起来。先前报道的肾细胞癌随机 3 期研究的数据用于考虑实体瘤研究中常见的并发事件，并说明不同的科学问题以及研究设计、数据收集、分析和解释的估计值选择的后果。
The estimand framework requires a precise definition of the clinical question of interest (the estimand) as different ways of accounting for "intercurrent" events post randomization may result in different scientific questions. The initiation of subsequent therapy is common in oncology clinical trials and is considered an intercurrent event if the start of such therapy occurs prior to a recurrence or progression event. Three possible ways to account for this intercurrent event in the analysis are to censor at initiation, consider recurrence or progression events (including death) that occur before and after the initiation of subsequent therapy, or consider the start of subsequent therapy as an event in and of itself. The new estimand framework clarifies that these analyses address different questions ("does the drug delay recurrence if no patient had received subsequent therapy?" vs "does the drug delay recurrence with or without subsequent therapy?" vs "does the drug delay recurrence or start of subsequent therapy?"). The framework facilitates discussions during clinical trial planning and design to ensure alignment between the key question of interest, the analysis, and interpretation. This article is a result of a cross-industry collaboration to connect the International Council for Harmonisation E9 addendum concepts to applications. Data from previously reported randomized phase 3 studies in the renal cell carcinoma setting are used to consider common intercurrent events in solid tumor studies, and to illustrate different scientific questions and the consequences of the estimand choice for study design, data collection, analysis, and interpretation.