Candidate binary endpoints are often considered as surrogates for time-to-event (TTE) clinical endpoints, primarily because they can be assessed at earlier time points. To be submitted for regulatory approval candidate binary endpoints need to validated. The most well-known method for performing such validation employs a meta-analytic framework to estimate individual-level and trial-level association. However, the performance of these association estimates in the context of a binary surrogate has not yet been examined through a comprehensive simulation study. This research aims to systematically investigate the performance of association estimates at the trial-level and at the individual-level under various trial design choices, using both simulation studies and clinical trial data, where available.

翻译：候选二元终点常被考虑作为时间至事件（TTE）临床终点的替代指标，主要原因是它们能在更早的时间点进行评估。为提交监管审批，候选二元终点需经过验证。最广为人知的验证方法采用元分析框架来估计个体水平与试验水平的关联性。然而，这些关联估计值在二元替代终点背景下的表现尚未通过全面的模拟研究进行检验。本研究旨在通过模拟研究及临床数据（若可用），系统性地考察在不同试验设计选择下，个体水平与试验水平关联估计值的表现。