A Poisson approach to the validation of failure time surrogate endpoints in individual patient data meta-analyses. (January 2019)

• Record Type: Journal Article
• Authors: Rotolo, Federico; Paoletti, Xavier; Burzykowski, Tomasz; Buyse, Marc; Michiels, Stefan
• Is Part Of: Statistical methods in medical research. Volume 28:Number 1(2019)
• Page Start: 170
• Page End: 183
• Publication Date: 2019-01
• Subjects: Surrogate endpoint -- failure time -- meta-analysis -- copula -- randomized trials; Medicine -- Research -- Statistical methods -- Periodicals; Research -- Periodicals; Review Literature -- Periodicals; Statistics -- methods -- Periodicals; Médecine -- Recherche -- Méthodes statistiques -- Périodiques; 610.727
• DOI: 10.1177/0962280217718582
• Languages: English
• ISSNs: 0962-2802

Abstract

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).