Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate the identification of MTD for model-assisted designs. Methods: The early completion performs based on each dose-assignment probability for multiple dosages. The formulas of probabilities are simple to calculate. We evaluated the early completion for an actual trial. In addition, a simulation study performed the percentage of correct MTD selection and early completion. Results: In the actual trial, the early completion could perform, and the MTD estimation phase could be shortened. In the simulation study, the change in the percentage of correct MTD selection from non-early completion version was 2.2% at the maximum, indicating that there was almost no decrease. In addition, depending on the toxicity rate, the percentage of correct MTD selection improved compared to the non-early completion version. The early completion performed from 18.1% to 90.8%. Conclusion: We propose the early completion method with not only little reduction in accuracy but also improving the percentage of correct MTD selection. We conclude the early completion can perform unproblematically for model-assisted design.
翻译:背景:第一阶段试验希望及早确定最大容许剂量(MTD),并迅速进入扩大组群或第二阶段试验,以确定功效。我们建议一种基于多种剂量的早期完成方法,以加速确定模型辅助设计所需的MTD。方法:根据多种剂量的每种剂量的剂量分配概率,早期完成表现;概率公式简单,可以计算;我们评估了实际试验的早期完成率。此外,一项模拟研究进行了正确的MTD选择和早期完成的百分比。结果:在实际试验中,早期完成可以进行,而MTD估计阶段可以缩短。在模拟研究中,正确选择MTD的百分比从非早期完成版本变化到最高为2.2%,表明几乎没有下降。此外,根据毒性率,正确的MTD选择比非早期完成版本改进了百分比。早期完成率从18.1%到90.8%不等。结论:我们提出早期完成方法,不仅没有多少精确性下降,而且还可以改进准确的MTD选择的百分比。我们完成了早期完成率。