Dose escalation with overdose control using a quasi-continuous toxicity score in cancer Phase I clinical trials
Dose escalation with overdose control using a quasi-continuous toxicity score in cancer Phase I clinical trials
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DOI：
10.1016/j.cct.2012.04.007
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发表时间：
2012-09-01
影响因子：
2.2
通讯作者：
Kowalski, Jeanne
中科院分区：
文献类型：
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作者：
Chen, Zhengjia;Tighiouart, Mourad;Kowalski, Jeanne
EWOC是一种贝叶斯自适应设计，用于在癌症I期临床试验中选择剂量水平，同时控制超过最大耐受剂量（MTD）的后验概率。EWOC已被临床医生用于设计许多癌症I期临床试验，参见例如[1-4]。然而，该设计将毒性反应视为剂量限制性毒性（DLT）的二元指标，并且未考虑患者在试验期间经历的毒性的数量和特定等级。Chen等人（2010年）提出了一种新的毒性评分系统，使用标准化等效毒性评分（NETS）充分利用所有毒性信息。在本文中，我们建议将NETS纳入EWOC使用准伯努利似然方法设计癌症I期临床试验。我们称之为使用标准化等效毒性评分（EWOC-NETS）进行过量控制的设计升级。模拟结果表明，该设计具有良好的操作特性，相对于EWOC（作为将毒性反应作为DLT的二元指标处理的代表设计），提高了MTD、试验效率、治疗效果和过量控制的准确性。我们使用真实的试验数据来说明这种设计在确定II期剂量方面的性能。(C)2012 Elsevier Inc. All rights reserved.
Escalation with overdose control (EWOC) is a Bayesian adaptive design for selecting dose levels in cancer Phase I clinical trials while controlling the posterior probability of exceeding the maximum tolerated dose (MTD). EWOC has been used by clinicians to design many cancer Phase I clinical trials, see e.g. [1-4]. However, this design treats the toxicity response as a binary indicator of dose limiting toxicity (DLT) and does not account for the number and specific grades of toxicities experienced by patients during the trial. Chen et al. (2010) proposed a novel toxicity score system to fully utilize all toxicity information using a normalized equivalent toxicity score (NETS). In this paper, we propose to incorporate NETS into EWOC using a quasi-Bernoulli likelihood approach to design cancer Phase I clinical trials. We call the design escalation with overdose control using normalized equivalent toxicity score (EWOC-NETS). Simulation results show that this design has good operating characteristics and improves the accuracy of MTD, trial efficiency, therapeutic effect, and overdose control relative to EWOC which is used as a representative of designs treating toxicity response as a binary indicator of DLT. We illustrate the performance of this design using real trial data in identifying the Phase ll dose. (C) 2012 Elsevier Inc. All rights reserved.