A new framework for semi-Markovian parametric multi-state models with interval censoring

Abstract

There are few computational and methodological tools available for the analysis of general multi-state models with interval censoring. Here, we propose a general framework for parametric inference with interval censored multi-state data. Our framework can accommodate any parametric model for the transition times, and covariates may be included in various ways. We present a general method for constructing the likelihood, which we have implemented in a ready-to-use R package, smms, available on GitHub. The R package also computes the required high-dimensional integrals in an efficient manner. Further, we explore connections between our modelling framework and existing approaches: our models fall under the class of semi-Markovian multi-state models, but with a different, and sparser parameterisation than what is often seen. We illustrate our framework through a dataset monitoring heart transplant patients. Finally, we investigate the effect of some forms of misspecification of the model assumptions through simulations.