Importance In a comparative trial, the time to a clinical event is often a key end point. However, the occurrence of a terminal event, such as death or premature study discontinuation, may preclude observation of this outcome. Although various methods for handling competing risks are available, no specific recommendations have been made for scenarios encountered in practice, especially when the terminal event profiles of the study arms are dissimilar. Moreover, appropriate methods for a desirable outcome, such as live hospital discharge, have seldom been discussed.

Observations Several of the most commonly used methods are reviewed. The first regards the terminal event as censoring and applies standard survival analysis to the event of interest. The between-group difference is usually summarized by the cause-specific hazard ratio. This summary measure is inappropriate when the new therapy markedly prolongs time to the terminal event. Moreover, the corresponding Kaplan-Meier curve for the end point of interest is uninterpretable. The second method is to use the cumulative incidence curve, which is the probability of experiencing the event of interest by each time point, acknowledging that patients who have died will never experience the event. However, the resulting pseudo hazard ratio is difficult to interpret. With a proper alternative summary measure, this approach works well for a desirable outcome but may not for an undesirable outcome. The third method focuses on the event-free survival time by combining information from occurrences of the terminal event and the event of interest simultaneously. This clinically interpretable method naturally accounts for differences in terminal event rates when comparing treatments with respect to the time to an undesirable outcome.

Conclusions and Relevance This article enhances our understanding of each method’s advantages and shortcomings and assists practitioners in choosing appropriate methods for handling competing risk problems in practice.

重要性 在比较试验中，临床事件发生的时间通常是一个关键终点。然而，终末事件的发生，例如死亡或过早终止研究，可能会妨碍对该结果的观察。尽管有各种处理竞争风险的方法，但没有针对实践中遇到的情况提出具体建议，特别是当研究组的最终事件概况不同时。此外，很少讨论获得理想结果的适当方法，例如现场出院。

观察 回顾了几种最常用的方法。第一个将最终事件视为审查并将标准生存分析应用于感兴趣的事件。组间差异通常由特定原因的风险比来概括。当新疗法显着延长至终末事件的时间时，这种汇总措施是不合适的。此外，兴趣终点的相应 Kaplan-Meier 曲线是无法解释的。第二种方法是使用累积发生率曲线，即每个时间点经历感兴趣事件的概率，承认已经死亡的患者永远不会经历该事件。然而，由此产生的伪风险比很难解释。通过适当的替代汇总措施，这种方法适用于理想的结果，但可能不适用于不理想的结果。第三种方法通过同时结合来自最终事件和感兴趣事件的发生信息来关注无事件生存时间。这种临床可解释的方法在比较治疗与不良结果的时间时自然解释了终末事件发生率的差异。

结论和相关性 本文增强了我们对每种方法的优点和缺点的理解，并帮助从业者选择适当的方法来处理实践中的竞争风险问题。