%0 Journal Article
%T A Poisson approach to the validation of failure time surrogate endpoints in individual patient data meta
%A Federico Rotolo
%A Marc Buyse
%A Stefan Michiels
%A Tomasz Burzykowski
%A Xavier Paoletti
%J Statistical Methods in Medical Research
%@ 1477-0334
%D 2019
%R 10.1177/0962280217718582
%X Surrogate endpoints are often used in clinical trials instead of well-established hard endpoints for practical convenience. The meta-analytic approach relies on two measures of surrogacy: one at the individual level and one at the trial level. In the survival data setting, a two-step model based on copulas is commonly used. We present a new approach which employs a bivariate survival model with an individual random effect shared between the two endpoints and correlated treatment-by-trial interactions. We fit this model using auxiliary mixed Poisson models. We study via simulations the operating characteristics of this mixed Poisson approach as compared to the two-step copula approach. We illustrate the application of the methods on two individual patient data meta-analyses in gastric cancer, in the advanced setting (4069 patients from 20 randomized trials) and in the adjuvant setting (3288 patients from 14 randomized trials)
%K Surrogate endpoint
%K failure time
%K meta-analysis
%K copula
%K randomized trials
%U https://journals.sagepub.com/doi/full/10.1177/0962280217718582