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.
翻译：目前,越来越多的临床试验选择混合剂作为更好的治疗对策的干预手段。然而,混合剂的剂量调查比单一剂复杂得多,因为混合剂量毒性的全序尚不清楚。因此,常规第一阶段的设计无法确定混合剂的最大耐用剂量(MTD),出于这种需要,提出了大量新的组合剂临床试验设计。现有设计如此之多,比较其性能的研究、探讨参数的影响和提供的建议非常有限。因此,我们进行了模拟研究,以评价多个阶段的第一阶段设计,其中提议在各种情况下为混合剂确定单一MTD。我们还探讨了不同设计参数的影响。最后,我们总结了每种设计的利弊,并提供了设计选择的一般准则。
相关内容
微信扫码咨询专知VIP会员