Marginal semiparametric transformation models for clustered multivariate competing risks data.

Abstract

Multivariate survival models are often used in studying multiple outcomes for right-censored data. However, the outcomes of interest often have competing risks, where standard multivariate survival models may lead to invalid inferences. For example, patients who had stem cell transplantation may experience multiple types of infections after transplant while reconstituting their immune system, where death without experiencing infections is a competing risk for infections. Such competing risks data often suffer from cluster effects due to a matched pair design or correlation within study centers. The cumulative incidence function (CIF) is widely used to summarize competing risks outcomes. Thus, it is often of interest to study direct covariate effects on the CIF. Most literature on clustered competing risks data analyses is limited to the univariate proportional subdistribution hazards model with inverse probability censoring weighting which requires correctly specifying the censoring distribution. We propose a marginal semiparametric transformation model for multivariate competing risks outcomes. The proposed model does not require modeling the censoring distribution, accommodates nonproportional subdistribution hazards structure, and provides a platform for joint inference of all causes and outcomes.