Proportional hazards mixed models

Abstract

We describe our recent work on mixed effects models for right-censored data. Vaida and Xu (2000) provided a general framework for handling random effects in proportional hazards (PH) regression, in a way similar to the linear, non-linear and generalized linear mixed effects models that allow random effects of arbitrary covariates. This general framework includes the frailty models as a special case. Maximum likelihood estimates of the regression parameters, the variance components and the baseline hazard, and empirical Bayes estimates of the random effects can be obtained via an MCEM algoritm. Variances of the parameter estimates are approximated using Louis' formula. We show interesting applications of the PH mixed effects model (PHMM) to a US Vietnam Era Twin Registry study on alcohol abuse, with the primary goal of identifying genetic contributions to such events. The twin pairs in the registry consist of monozygotic and dizygotic twins. After model fitting and for interpretation purposes, the proportional hazards formulation is converted to a linear transformation model before the results on genetic contributions are reported. The model also allows examination of gene and covariate interactions, as well as the modelling of multivariate outcomes (comorbidities).