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临床试验中的竞争风险:它们重要吗?我们应该如何考虑它们?

Competing Risks in Clinical Trials: Do They Matter and How Should We Account for Them?

机构信息

Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.

出版信息

J Am Coll Cardiol. 2024 Sep 10;84(11):1025-1037. doi: 10.1016/j.jacc.2024.06.023.

Abstract

During patient follow-up in a randomized trial, some deaths may occur. Where death (or noncardiovascular death) is not part of an outcome of interest it is termed a competing risk. Conventional analyses (eg, Cox proportional hazards model) handle death similarly to other censored follow-up. Patients still alive are unrealistically assumed to be representative of those who died. The Fine and Gray model has been used to handle competing risks, but is often used inappropriately and can be misleading. We propose an alternative multiple imputation approach that plausibly accounts for the fact that patients who die tend also to be at high risk for the (unobserved) outcome of interest. This provides a logical framework for exploring the impact of a competing risk, recognizing that there is no unique solution. We illustrate these issues in 3 cardiovascular trials and in simulation studies. We conclude with practical recommendations for handling competing risks in future trials.

摘要

在随机试验的患者随访期间,可能会发生一些死亡事件。如果死亡(或非心血管死亡)不属于关注结局的一部分,则称之为竞争风险。传统分析(例如,Cox 比例风险模型)将死亡与其他删失随访同等处理。仍存活的患者被不合理地假设为死亡患者的代表。Fine 和 Gray 模型已被用于处理竞争风险,但经常被不恰当地使用,并且可能具有误导性。我们提出了一种替代的多重插补方法,合理考虑了死亡患者也往往具有高风险的(未观察到的)关注结局的事实。这为探索竞争风险的影响提供了一个合理的框架,同时认识到不存在唯一的解决方案。我们在 3 项心血管试验和模拟研究中说明了这些问题。最后,我们提出了未来试验中处理竞争风险的实用建议。

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