Evaluating thetime-dependentpredictive accuracy forevent-to-timeoutcome with a cure fraction

摘要

In medical studies, it is often observed that a portion of subjects will never experience the event of interest and thus can be treated as cured or long-term survivors. Many populations of early-stage cancer patients contain both uncured and cured individuals that should be modeled using cure models. In prognostic studies, the cure status (uncure or cure) is an issue of interest for medical practitioners, and the disease status (death or alive) of an individual is not a fixed characteristic and it varies along the time. These statuses are usually predicted by a prognostic risk score. The time-dependent receiver operating characteristic (ROC) curve is a powerful tool to evaluate these predicting performances dynamically. In the context with a cure fraction, quantifying and estimating the predictive performances of the risk score is a challenge since the disease status and cure status are both unknown among individuals who are censored. In this paper, to assess the predictive accuracy for the survival outcome with a cure fraction, we propose a time-dependent ROC curve semi-parametric estimator based on the sieve maximum likelihood (ML) estimation under the mixture cure model. We also apply a Bernstein-based smoothing method in the estimation procedure, and this estimator can lead to substantial gain in efficiency. In addition, we derive the time-dependent area under the ROC curve (AUC) to summarize the discriminatory capacity of the risk score globally. Finally, we evaluate the finite sample performance of the proposed methods by extensive simulations and illustrate the estimation using two real data sets, one from a melanoma study and the other from stomach cancer.