论文标题
剂量查找有关迟到安全性和功效结果的治疗的研究
Dose Finding Studies for Therapies with Late-Onset Safety and Efficacy Outcomes
论文作者
论文摘要
在I/II期剂量调查试验中，目的是找到最佳的生物剂量（OBD），该剂量既安全又有效，可以最大程度地基于安全性和功效来最大程度地提高一些最佳标准。当研究的治疗包括多个治疗周期，并且在整个多个周期的随访过程中，毒性和功效结果可能发生在任何时刻。在这项工作中，我们介绍了基于众所周知的Tite-Crm的延迟发作毒性和功效的基于模型的tite-Crm。发现它优于目前可用的替代设计，这些设计解释了延迟发作双变量结果。一种模型辅助方法和双变量生存设计，并且在直观和计算上都是可行的。
In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when the investigated treatment consists of multiple cycles of therapy, and both toxicity and efficacy outcomes may occur at any point throughout the follow up of multiple cycles. In this work we present the Joint TITE-CRM, a model-based design for late onset toxicities and efficacies based on the well-known TITE-CRM. It is found to be superior to both currently available alternative designs that account for late onset bivariate outcomes; a model-assisted method and a bivariate survival design, as well as being both intuitive and computationally feasible.
