Estimating the turning point of the log-logistic hazard function in the presence of long-term survivors with an application for uterine cervical cancer data

Abstract

The hazard function plays an important role in cancer patient survival studies, as it quantifies the instantaneous risk of death of a patient at any given time. Often in cancer clinical trials, unimodal hazard functions are observed, and it is of interest to detect (estimate) the turning point (mode) of hazard function, as this may be an important measure in patient treatment strategies with cancer. Moreover, when patient cure is a possibility, estimating cure rates at different stages of cancer, in addition to their proportions, may provide a better summary of the effects of stages on survival rates. Therefore, the main objective of this paper is to consider the problem of estimating the mode of hazard function of patients at different stages of cervical cancer in the presence of long-term survivors. To this end, a mixture cure rate model is proposed using the log-logistic distribution. The model is conveniently parameterized through the mode of the hazard function, in which cancer stages can affect both the cured fraction and the mode. In addition, we discuss aspects of model inference through the maximum likelihood estimation method. A Monte Carlo simulation study assesses the coverage probability of asymptotic confidence intervals.