A Simulation Study Evaluating Phase I Clinical Trial Designs for Combinational Agents

TL;DR

This paper conducts a comprehensive simulation study to evaluate and compare various phase I clinical trial designs for combinational agents, aiming to identify the most effective methods for dose-finding in complex scenarios.

Contribution

It provides a systematic comparison of multiple novel phase I designs for combinational agents and offers practical guidelines for their selection based on performance analysis.

Findings

Certain designs outperform others in specific scenarios

Parameter choices significantly influence design performance

Guidelines for selecting appropriate designs are proposed

Abstract

Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of combination dose toxicity is unknown. Therefore, regular phase I designs are not able to identify the maximum tolerated dose (MTD) of combinational agents. Motivated by such needs, plenty of novel phase I clinical trial designs for combinational agents were proposed. With so many available designs, research that compare their performances, explore parameters' impacts, and provide recommendations is very limited. Therefore, we conducted a simulation study to evaluate multiple phase I designs that proposed to identify single MTD for combinational agents under various scenarios. We also explored influences of different design parameters. In the end, we summarized the pros and cons of each design, and provided a general guideline in design selection.