Meta-analysis of pairs of survival curves under heterogeneity: a Poisson correlated gamma-frailty approach.

We address the problem of meta-analysis of pairs of survival curves under heterogeneity. Starting point for the meta-analysis is a set of studies, each comparing the same two treatments, containing information about multiple survival outcomes. Under heterogeneity, we model the number of events using an extension of the Poisson correlated gamma-frailty model with serial within-arm and positive between-arm correlations. The parameters of the models are estimated following a two-stage estimation procedure. In the first stage the underlying hazards and between-study variance are estimated using the marginals, while a second stage is used to estimate both within-arm and between-arm correlations. The methodology is illustrated with an observational study on breast cancer.