Predicting analysis times in randomized clinical trials with cancer immunotherapy

BACKGROUND A new class of immuno-oncology agents has recently been shown to induce long-term survival in a proportion of treated patients. This phenomenon poses unique challenges for the prediction of analysis time in event-driven studies. If the phenomenon of long-term survival is not accounted for properly, the accuracy of the prediction based on the existing methods may be substantially compromised. METHODS Parametric mixture cure rate models with the best fit to empirical clinical trial data were proposed to predict analysis times in immuno-oncology studies during the course of the study. The proposed prediction procedure also accounts for the mechanism of action introduced by cancer immunotherapies, such as delayed and long-term survival effects. RESULTS The proposed methodology was retrospectively applied to a randomized phase III immuno-oncology clinical trial. Among various parametric mixture cure rate models, the Weibull cure rate model was found to be the best-fitting model for this study. The unique survival kinetics of cancer immunotherapy was captured in the longitudinal predictions of the final analysis times. CONCLUSIONS Parametric mixture cure rate models, along with estimated long-term survival rates, probabilities of study incompletion, and expected statistical powers over time, provide immuno-oncology clinical trial researchers with a useful tool for continuous event monitoring and prediction of analysis times, such that informed decisions with quantifiable risks can be made for better resource and logistic planning.