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.
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