An adaptive dose-finding design incorporating both toxicity and efficacy
An adaptive dose-finding design incorporating both toxicity and efficacy
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DOI：
10.1002/sim.2325
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发表时间：
2006-07-30
影响因子：
2
通讯作者：
Mandrekar, Sumithra
中科院分区：
文献类型：
--
作者：
Zhang, Wei;Sargent, Daniel J.;Mandrekar, Sumithra
新疗法正在挑战药物开发的标准。具有特定生物靶点和有限毒性的药物需要新的设计来确定用于更大规模研究的剂量。在本文中，我们描述了一种方法，将毒性和疗效的数据到估计的生物最佳剂量的代理在I期试验。该方法基于灵活的连续比模型，并使用简单的最佳剂量选择标准。剂量选择基于直至该时间点接受治疗的所有患者，使用持续再评估方法。考虑的剂量-结果曲线包括单调递增、单调递减和单峰曲线。我们的模拟研究表明，所提出的设计，我们称之为TriCRM，具有良好的操作特性。版权所有（c）2005年约翰威利父子有限公司。
Novel therapies are challenging the standards of drug development. Agents with specific biologic targets and limited toxicity require novel designs to determine doses to be taken forward into larger studies. In this paper, we describe an approach that incorporates both toxicity and efficacy data into the estimation of the biologically optimal dose of an agent in a phase I trial. The approach is based on the flexible continuation-ratio model, and uses straightforward optimal dose selection criteria. Dose selection is based on all patients treated up until that time point, using a continual reassessment method approach. Dose-outcome curves considered include monotonically increasing, monotonically decreasing, and unimodal curves. Our simulation studies demonstrate that the proposed design, which we call TriCRM, has favourable operating characteristics. Copyright (c) 2005 John Wiley & Sons, Ltd.