A curve-free method for Phase I clinical trials
A curve-free method for Phase I clinical trials
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DOI：
10.1111/j.0006-341x.2000.00609.x
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发表时间：
2000-06-01
期刊：
影响因子：
1.9
通讯作者：
Eisele, J
中科院分区：
文献类型：
--
作者：
Gasparini, M;Eisele, J
考虑找到尽可能高的剂量的问题，以具有受控的毒性率。这个问题在肿瘤学I期临床试验中很常见。这种剂量通常被称为最大耐受剂量（MTD），因为它代表了疗效和毒性之间的必要权衡。连续再评估法（CRM）是对传统的上下法估计MTD的改进。它基于贝叶斯方法，并假设剂量-毒性关系遵循特定的反应曲线，例如，逻辑或功率曲线。本文的目的是说明如何在CRM中使用的特定曲线的假设是没有必要的，实际上可以阻碍有效地利用先前的输入。提出了一种替代的无曲线方法，其中毒性的概率直接建模为一个未知的多维参数。为了这个目的，一个产品的β先验（PBP）的介绍，并显示带来逻辑上的改进。仿真结果表明，实际的改进。
Consider the problem of finding the dose that is as high as possible subject to having a controlled rate of toxicity. The problem is commonplace in oncology Phase I clinical trials. Such a dose is often called the maximum tolerated dose (MTD) since it represents a necessary trade-off between efficacy and toxicity. The continual reassessment method (CRM) is an improvement over traditional up-and-down schemes for estimating the MTD. It is based on a Bayesian approach and on the assumption that the dose-toxicity relationship follows a specific response curve, e.g., the logistic or power curve. The purpose of this paper is to illustrate how the assumption of a specific curve used in the CRM is not necessary and can actually hinder the efficient use of prior inputs. An alternative curve-free method in which the probabilities of toxicity are modeled directly as an unknown multidimensional parameter is presented. To that purpose, a product-of-beta prior (PBP) is introduced and shown to bring about logical improvements. Practical improvements are illustrated by simulation results.