Dose-finding design based on level set estimation in phase I cancer clinical trials
This work addresses the safety and efficacy challenges in phase I cancer clinical trials, offering an incremental improvement over existing dose-finding methods.
The authors tackled the problem of finding the maximum tolerated dose (MTD) in phase I cancer clinical trials by framing it as a level set estimation problem and proposing a novel dose-finding design. Simulation results showed that this design achieves higher accuracy in estimating the MTD and involves lower risk of overdosing compared to existing designs.
The primary objective of phase I cancer clinical trials is to evaluate the safety of a new experimental treatment and to find the maximum tolerated dose (MTD). We show that the MTD estimation problem can be regarded as a level set estimation (LSE) problem whose objective is to determine the regions where an unknown function value is above or below a given threshold. Then, we propose a novel dose-finding design in the framework of LSE. The proposed design determines the next dose on the basis of an acquisition function incorporating uncertainty in the posterior distribution of the dose-toxicity curve as well as overdose control. Simulation experiments show that the proposed LSE design achieves a higher accuracy in estimating the MTD and involves a lower risk of overdosing allocation compared to existing designs, thereby indicating that it provides an effective methodology for phase I cancer clinical trial design.