随着肿瘤学治疗的持续发展，以及生存率的提高，基于总生存期等终点的临床试验可能需要长期的随访期来观察足够的事件并确保充分的统计力量。随着随访时间的增加，研究的可行性可能会受到影响。使用代理终点而不是最终终点，可能对这些研究具有吸引力。然而，在代理可以用于临床试验之前，必须经过统计验证。在本文中，我们提出了一种验证代理的方法，当代理和最终终点的事件时间均被审查时，该方法是基于荟萃分析数据开发的，并使用介导分析将治疗对最终终点的总效应分解为直接效应和经由代理的间接效应。数据的荟萃性质在试验水平上使用随机效应的联合模型进行考虑。通过模型参数计算治疗对最终终点的间接效应占总效应的比例，并将其用作代理的度量。我们应用此方法，研究了可切除胃癌中复发时间作为总生存期的代理终点。©作者2022。牛津大学出版社发表。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。

With the ongoing development of treatments and the resulting increase in survival in oncology, clinical trials based on endpoints such as overall survival may require long follow-up periods to observe sufficient events and ensure adequate statistical power. This increase in follow-up time may compromise the feasibility of the study. The use of surrogate endpoints instead of final endpoints may be attractive for these studies. However, before a surrogate can be used in a clinical trial, it must be statistically validated. In this article, we propose an approach to validate surrogates when both the surrogate and final endpoints are censored event times. This approach is developed for meta-analytic data and uses a mediation analysis to decompose the total effect of the treatment on the final endpoint as a direct effect and an indirect effect through the surrogate. The meta-analytic nature of the data is accounted for in a joint model with random effects at the trial level. The proportion of the indirect effect over the total effect of the treatment on the final endpoint can be computed from the parameters of the model and used as a measure of surrogacy. We applied this method to investigate time-to-relapse as a surrogate endpoint for overall survival in resectable gastric cancer.© The Author 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.