Semiparametric Normal Transformation Models for Spatially Correlated Survival Data

Abstract

There is an emerging interest in modeling spatially correlated survival data in biomedical and epidemiologic studies. In this article we propose a new class of semiparametric normal transformation models for right-censored spatially correlated survival data. This class of models assumes that survival outcomes marginally follow a Cox proportional hazard model with unspecified baseline hazard, and their joint distribution is obtained by transforming survival outcomes to normal random variables, whose joint distribution is assumed to be multivariate normal with a spatial correlation structure. A key feature of the class of semiparametric normal transformation models is that it provides a rich class of spatial survival models where regression coefficients have population average interpretation and the spatial dependence of survival times is conveniently modeled using the transformed variables by flexible normal random fields. We study the relationship of the spatial correlation structure of the transformed normal variables and the dependence measures of the original survival times. Direct nonparametric maximum likelihood estimation in such models is practically prohibited due to the high-dimensional intractable integration of the likelihood function and the infinite-dimensional nuisance baseline hazard parameter. We hence develop a class of spatial semiparametric estimating equations, which conveniently estimate the population-level regression coefficients and the dependence parameters simultaneously. We study the asymptotic properties of the proposed estimators and show that they are consistent and asymptotically normal. The proposed method is illustrated with an analysis of data from the East Boston Asthma Study, and its performance is evaluated using simulations.