Gaussian Copula Regression Modeling for Marker Classification Metrics with Competing Risk Outcomes

Abstract

Decisions regarding competing risks are usually based on a continuous-valued marker toward predicting a cause-specific outcome. The classification power of a marker can be summarized using the time-dependent receiver operating characteristic curve and the corresponding area under the curve (AUC). This paper proposes a Gaussian copula-based model to represent the joint distribution of the continuous-valued marker, the overall survival time, and the cause-specific outcome. Then, it is used to characterize the time-varying ROC curve in the context of competing risks. Covariate effects are incorporated by linking linear components to the skewed normal distribution for the margin of the marker, a parametric proportional hazards model for the survival time, and a logit model for the cause of failure. Estimation is carried out using maximum likelihood, and a bootstrap technique is implemented to obtain confidence intervals for the AUC. Information-criteria strategies are employed to find a parsimonious model. The performance of the proposed model is evaluated in simulation studies, considering different sample sizes and censoring distributions. The methods are illustrated with the reanalysis of a prostate cancer clinical trial. The joint regression strategy produces a straightforward and flexible model of the time-dependent ROC curve in the presence of competing risks, enhancing the understanding of how covariates may affect the discrimination of a marker.