A Tutorial for Evaluating Cure Model Appropriateness

Abstract

In survival analysis, traditional models assume all individuals will eventually experience the event of interest. However, advances in therapeutics have led to multiple clinical contexts with potentially curative therapies, and in these contexts, certain individuals may never experience the event. Statisticians have developed cure models as a methodology to address this challenge. Nonetheless, despite significant statistical advances in cure models, we have seen more limited uptake in biomedical applications, and we hypothesize that this is caused by limited guidance in the appropriate application of cure models. Cure models require specific identifiability conditions for valid parameter estimation, and previous reports have demonstrated significant issues with the inappropriate application of cure models. Existing tutorials for cure models focus on model implementation and either assume or provide only limited guidance on whether cure modeling is appropriate for the given dataset. This tutorial addresses this gap by describing a systematic procedure that integrates clinical judgment, visual inspection of Kaplan-Meier curves, and quantitative evaluation. We provide a worked example using data from a randomized clinical trial in acute myeloid leukemia, and we also summarize findings from a series of other datasets of hematopoietic cell transplantation to suggest broad practical guidance for choosing to apply cure models. By systematically evaluating cure model appropriateness before fitting these models, researchers can achieve more reliable survival analysis and improved clinical decision-making.