Recently, the strategy for dose optimization in oncology has shifted to conduct Phase 2 randomized controlled trials with multiple doses. Optimal biologic dose selection from Phase 1 trial data to determine candidate doses for Phase 2 trials has been gaining attention. This study proposes a novel adaptive cohort size determination method for optimal biologic dose-finding to accelerate trials. The cohort size expansion is determined adaptively depending on the toxicity and efficacy data of the ongoing trial. In a simulation, the proposed method shortened the trial duration and maintained accuracy. The trial duration was reduced by an average of approximately 20% compared with the non-adaptive cohort size determination design. The cohort size expansion is demonstrated using a simple example.
翻译:近期,肿瘤学领域剂量优化策略已转向开展含多个剂量的Ⅱ期随机对照试验。基于Ⅰ期试验数据筛选最优生物学剂量以确定Ⅱ期试验候选剂量的方法正受到广泛关注。本研究提出一种新颖的自适应队列规模确定方法,用于加速最优生物学剂量探索。队列规模扩增将根据正在开展的试验中获得的毒性与有效性数据进行自适应调整。模拟实验表明,所提方法在保持准确性的同时缩短了试验周期。相较于非自适应队列规模确定设计,试验周期平均缩短约20%。通过简单实例验证了队列规模扩增的效果。