Designs for single- or multiple-agent phase I trials
Designs for single- or multiple-agent phase I trials
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DOI：
10.1111/j.0006-341x.2004.00215.x
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发表时间：
2004-09-01
期刊：
影响因子：
1.9
通讯作者：
Peddada, SD
中科院分区：
文献类型：
--
作者：
Conaway, MR;Dunbar, S;Peddada, SD
肿瘤细胞毒性药物的I期试验通常是涉及单一细胞毒性药物的剂量探索研究。已经提出了许多统计方法，这些试验，所有这些都是基于一个单调的剂量-毒性曲线的假设。对于单药试验，这是一个有效的假设。然而，在许多试验中，研究人员感兴趣的是基于逐步增加的多种细胞毒性药物找到最大耐受剂量。当有多种药物时，剂量-毒性曲线的单调性没有明确定义。在这篇文章中，我们提出了一个设计的I期试验中，毒性概率遵循偏序，这意味着有对治疗的毒性概率的顺序是未知的，在开始的试验。我们比较新的设计，现有的方法简单的订单和调查的性质的设计两个部分订单。
Phase I trials of cytotoxic agents in oncology are usually dose-finding studies that involve a single cytotoxic agent. Many statistical methods have been proposed for these trials, all of which are based on the assumption of a monotonic dose-toxicity curve. For single-agent trials, this is a valid assumption. In many trials, however, investigators are interested in finding the maximally tolerated dose based on escalating multiple cytotoxic agents. When there are multiple agents, monotonicity of the dose-toxicity curve is not clearly defined. In this article we present a design for phase I trials in which the toxicity probabilities follow a partial order, meaning that there are pairs of treatments for which the ordering of the toxicity probabilities is not known at the start of the trial. We compare the new design to existing methods for simple orders and investigate the properties of the design for two partial orders.