Meta-analytic evaluation of surrogate endpoints at multiple time points in randomized controlled trials with time-to-event endpoints.

ABSTRACT:

Background

Valid surrogate endpoints are of great interest for efficient evaluation of novel therapies. With surrogate and true time-to-event endpoints, meta-analytic approaches for surrogacy validation commonly rely on the hazard ratio, ignore that randomized trials possibly contribute to the meta-analysis for different follow-up durations, overlook the importance of the time lag between surrogate and true endpoints in determining surrogate utility, and assume that treatment effects and the strength of surrogacy remain constant over time. In this context, we introduce a novel two-stage meta-analytic model to evaluate trial-level surrogacy.

Methods

Our model employs restricted mean survival time (RMST) differences to quantify treatment effects at the first stage. At the seco

SUBMITTER: Tang X 

PROVIDER: S-EPMC12614294 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature