Marginal proportional hazards models for multivariate interval-censored data

Biometrika. 2023 Sep;110(3):815-830. doi: 10.1093/biomet/asac059. Epub 2022 Nov 2.

Abstract

Multivariate interval-censored data arise when there are multiple types of events or clusters of study subjects, such that the event times are potentially correlated and when each event is only known to occur over a particular time interval. We formulate the effects of potentially time-varying covariates on the multivariate event times through marginal proportional hazards models while leaving the dependence structures of the related event times unspecified. We construct the nonparametric pseudolikelihood under the working assumption that all event times are independent, and we provide a simple and stable EM-type algorithm. The resulting nonparametric maximum pseudolikelihood estimators for the regression parameters are shown to be consistent and asymptotically normal, with a limiting covariance matrix that can be consistently estimated by a sandwich estimator under arbitrary dependence structures for the related event times. We evaluate the performance of the proposed methods through extensive simulation studies and present an application to data from the Atherosclerosis Risk in Communities Study.

Keywords: Cox model; Expectation-maximization algorithm; Interval censoring; Multivariate failure time data; Nonparametric likelihood; Pseudolikelihood; Sandwich variance estimator; Simultaneous inference; Time-varying covariate.