Dose-finding design based on level set estimation in phase I cancer clinical trials

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.

@article{seno2025_2504.09157,
  title={ Dose-finding design based on level set estimation in phase I cancer clinical trials },
  author={ Keiichiro Seno and Kota Matsui and Shogo Iwazaki and Yu Inatsu and Shion Takeno and Shigeyuki Matsui },
  journal={arXiv preprint arXiv:2504.09157},
  year={ 2025 }
}