Unifying CRM and EWOC designs for phase I cancer clinical trials
Unifying CRM and EWOC designs for phase I cancer clinical trials
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DOI：
10.1016/j.jspi.2008.07.005
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发表时间：
2009-03-01
影响因子：
0.9
通讯作者：
Shih, Weichung Joe
中科院分区：
文献类型：
--
作者：
Chu, Pei-Ling;Lin, Yong;Shih, Weichung Joe
I期癌症临床试验的主要目标是确定在可接受的毒性水平下新疗法的最高剂量，以便在随后的II期试验中使用。持续再评估方法（CRM） [J]。佩佩，M.，费希尔，L., 1990。持续再评估方法：癌症I期临床试验的实用设计。杨建军，张建军，张建军，等。生物识别技术在药物过量控制中的应用[J]。癌症I期临床试验：有效剂量递增与过量控制。中央集权。Med. 17(10)， 1103-1120是用于I期癌症临床试验的两种基于模型的设计。许多作者对（原来的）CRM和EWOC做了一些修改。在本文中，我们展示了CRM和EWOC如何统一并呈现混合设计。研究了混合设计方法的特点。通过收敛率和过量比例对三种设计（CRM、EWOC和混合设计）进行了比较。仿真结果表明，混合设计通常具有比EWOC更快的收敛速度和比CRM更小的过量比例，特别是当真实最大耐受剂量（MTD）高于所考虑剂量范围的中间水平时。这三种设计的性能也在对异常值的敏感性方面进行了评估。(C) 2008 Elsevier B.V.版权所有
The main goal of phase I cancer clinical trials is to determine the highest dose of a new therapy associated with an acceptable level of toxicity for the use in a subsequent phase II trial. The continual reassessment method (CRM) [O'Quigley,J., Pepe, M., Fisher, L., 1990. Continual reassessment method: a practical design for phase I clinical trials in cancer. Biometrics 46, 33-481 and escalation with overdose control (EWOC) [Babb, J., Rogatko, A., Zacks, S., 1998. Cancer phase I clinical trials: efficient dose escalation with overdose control. Statist. Med. 17 (10), 1103-1120 are two model-based designs used for phase I cancer clinical trials. A few modifications of the (original) CRM and EWOC have been made by many authors. In this paper, we show how CRM and EWOC can be unified and present a hybrid design. We study the characteristics of the approach of the hybrid design. The comparisons of the three designs (CRM, EWOC, and the hybrid design) are presented by convergence rates and overdose proportions. The simulation results show that the hybrid design generally has faster convergence rates than EWOC and smaller overdose proportions than CRM, especially when the true maximum tolerated dose (MTD) is above the mid-level of the dose range considered. The performance of these three designs is also evaluated in terms of sensitivity to outliers. (C) 2008 Elsevier B.V. All rights reserved.