Keyboard design for phase I drug-combination trials
Keyboard design for phase I drug-combination trials
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DOI：
10.1016/j.cct.2020.105972
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发表时间：
2020-05-01
影响因子：
2.2
通讯作者：
Yuan, Ying
中科院分区：
文献类型：
--
作者：
Pan, Haitao;Lin, Ruitao;Yuan, Ying
键盘设计是一种新的模型辅助剂量查找方法，用于寻找单药试验的最大耐受剂量（MTD）。与更复杂的模型辅助设计相比，键盘设计易于实现，性能优越。在本文中，我们将键盘设计扩展到双药剂量测定试验。提出的Keyboard组合试验设计保持了原始单药Keyboard设计的简洁性，其剂量递增和降递增规则可以在试验前预先制表。我们证明了键盘组合设计具有理想的理论性质，包括其决策规则的最优性、剂量转移的相干性和向目标剂量的收敛性。采用一种新颖的随机二维剂量-毒性情景生成算法，进行了广泛的模拟，以评估所提出的键盘组合设计的性能。仿真结果证实了该键盘设计具有理想的、具有竞争力的工作特性。一个R Shiny应用程序可在www.trialdesign.org上实现键盘组合设计。
The Keyboard design is a novel model-assisted dose-finding method to find the maximum tolerated dose (MTD) for single-agent trials. The Keyboard design is easy to implement and has superior performance in comparison to more complicated model-assisted designs. In this article, we extend the Keyboard design to dual-agent dose-finding trials. The proposed Keyboard combination trial design maintains the simplicity of the original single-agent Keyboard design, and its dose escalation and deescalation rules can be pre-tabulated before conducing the trial. We show that the Keyboard combination design has desirable theoretical properties, including the optimality of its decision rules, coherence in dose transition, and convergence to the target dose. Extensive simulations are conducted to evaluate the performance of the proposed Keyboard combination design using a novel, random two-dimensional dose-toxicity scenario generating algorithm. The simulation results confirm the desirable and competitive operating characteristics of the Keyboard design. An R Shiny application is available at www.trialdesign.org to implement the Keyboard combination design.