Implementation of ICH E9 (R1): A Few Points Learned During the COVID-19 Pandemic.
Implementation of ICH E9 (R1): A Few Points Learned During the COVID-19 Pandemic.
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ICH E9 （R1）的实施：在COVID-19大流行期间学到的几点。
DOI：
10.1007/s43441-021-00297-6
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发表时间：
2021-09
影响因子：
1.5
通讯作者：
Lipkovich I
中科院分区：
文献类型：
--
作者：
Qu Y;Lipkovich I
当前的COVID-19大流行给正在进行的临床试验带来了许多挑战，并为临床试验中现有的估算原则和实践提供了压力测试环境。大流行可能会增加并发事件（ICEs）和缺失值的发生率，从而引发大量关于修订议定书和统计分析计划的讨论，以解决这些问题。在本文中，我们回顾了最近关于估计和缺失值处理的研究，特别是ICH E9 （R1）关于临床试验估计和敏感性分析的附录。基于对使用因果推理框架处理ice的策略的深入讨论，我们建议在ICH E9 （R1）中应用估计和估计框架进行一些改进。具体来说，我们讨论了多种策略，使我们能够根据ice的原因以不同的方式处理ice。我们还建议主要通过假设策略来处理ice，并提供了针对不同类型ice的不同假设策略的示例，以及估算和敏感性分析的路线图。我们的结论是，提出的框架有助于简化将临床目标转化为统计推断目标的过程，并自动解决由诸如大流行等事件引起的定义估计和选择估计程序的许多问题。
The current COVID-19 pandemic poses numerous challenges for ongoing clinical trials and provides a stress-testing environment for the existing principles and practice of estimands in clinical trials. The pandemic may increase the rate of intercurrent events (ICEs) and missing values, spurring a great deal of discussion on amending protocols and statistical analysis plans to address these issues. In this article, we revisit recent research on estimands and handling of missing values, especially the ICH E9 (R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials. Based on an in-depth discussion of the strategies for handling ICEs using a causal inference framework, we suggest some improvements in applying the estimand and estimation framework in ICH E9 (R1). Specifically, we discuss a mix of strategies allowing us to handle ICEs differentially based on reasons for ICEs. We also suggest ICEs should be handled primarily by hypothetical strategies and provide examples of different hypothetical strategies for different types of ICEs as well as a road map for estimation and sensitivity analyses. We conclude that the proposed framework helps streamline translating clinical objectives into targets of statistical inference and automatically resolves many issues with defining estimands and choosing estimation procedures arising from events such as the pandemic.
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