Semi Parametric Survival Analysis Via Dirichlet Process Mixtures Of The First Hitting Time Model PDF Download

Time-to-event data often violate the proportional hazards assumption inherent in the popular Cox regression model. Such violations are especially common in the sphere of biological and medical data where latent heterogeneity due to unmeasured covariates or time varying effects are common. A variety of parametric survival models have been proposed which make more appropriate assumptions on the hazard function, at least for certain applications. One such model is derived from the First Hitting Time (FHT) paradigm which assumes that a subject's event time is determined by a latent stochastic process reaching a threshold value. Several random effects specifications of the FHT model have also been proposed which allow for better modeling of data with unmeasured covariates. While often appropriate, these methods often display limited flexibility due to their inability to model a wide range of heterogeneities. To address this issue, we propose two Bayesian models which loosen assumptions on the mixing distribution inherent in the random effects FHT models currently in use. The first proposed model is ideally suited for standard regression analyses. The second model is designed for use in clinical trials where survival is the outcome of interest. We demonstrate via simulation study that the proposed models greatly improve both survival and parameter estimation in the presence of latent heterogeneity. We also apply the proposed methodologies to data from a toxicology/carcinogenicity study which exhibits nonproportional hazards and contrast the results with competing methods.