A modified toxicity probability interval method for dose-finding trials.
A modified toxicity probability interval method for dose-finding trials.
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DOI：
10.1177/1740774510382799
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发表时间：
2010-12
期刊：
影响因子：
--
通讯作者：
Bekele BN
中科院分区：
文献类型：
--
作者：
Ji Y;Liu P;Li Y;Bekele BN
在早期工作的基础上，毒性概率区间（TPI）方法，我们提出了一个修改的TPI（mTPI）设计，是校准的I期试验。我们的目标是改进试验的实施，提供更有效的设计，同时保持原始TPI设计的简单性。与TPI方法一样，mTPI由简单贝叶斯模型的后验推断指导的实用剂量确定方案组成。然而，新方法提出了改进的剂量发现决策规则的基础上，一个新的统计，单位概率质量（UPM）。对于给定的区间和概率分布，UPM被定义为区间的概率质量与区间长度的比值。通过使用UPM进行剂量确定的改进有三个方面：（1）mTPI方法似乎比TPI方法更安全，因为它使更少的患者接受毒性剂量;（2）mTPI方法消除了校准两个关键参数的需要，这是TPI方法所需的，也是已知的困难问题;以及（3）mTPI方法对应于决策理论框架下的贝叶斯规则，并且具有额外的期望的大样本和小样本性质。所提出的方法适用于具有二元毒性终点的剂量探索试验。新方法mTPI基本上是免校准的，并且表现出比TPI方法更好的性能。这些特征使mTPI成为实际试验设计的理想选择。
Building on earlier work, the toxicity probability interval (TPI) method, we present a modified TPI (mTPI) design that is calibration-free for phase I trials. Our goal is to improve the trial conduct and provide more effective designs while maintaining the simplicity of the original TPI design. Like the TPI method, the mTPI consists of a practical dose-finding scheme guided by the posterior inference for a simple Bayesian model. However, the new method proposes improved dose-finding decision rules based on a new statistic, the unit probability mass (UPM). For a given interval and a probability distribution, the UPM is defined as the ratio of the probability mass of the interval to the length of the interval. The improvement through the use of the UPM for dose finding is threefold: (1) the mTPI method appears to be safer than the TPI method in that it puts fewer patients on toxic doses; (2) the mTPI method eliminates the need for calibrating two key parameters, which is required in the TPI method and is a known difficult issue; and (3) the mTPI method corresponds to the Bayes rule under a decision theoretic framework and possesses additional desirable large- and small-sample properties. The proposed method is applicable to dose-finding trials with a binary toxicity endpoint. The new method mTPI is essentially calibration free and exhibits improved performance over the TPI method. These features make the mTPI a desirable choice for the design of practical trials.
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影响因子：
2
作者：
GOODMAN, SN;ZAHURAK, ML;PIANTADOSI, S
通讯作者：
PIANTADOSI, S
影响因子：
1.9
作者：
OQUIGLEY, J;PEPE, M;FISHER, L
通讯作者：
FISHER, L
影响因子：
1.9
作者：
Cheung, YK;Chappell, R
通讯作者：
Chappell, R
影响因子：
2.7
作者：
Garrett-Mayer, E
通讯作者：
Garrett-Mayer, E
影响因子：
2.7
作者：
Shen, LZ;OQuigley, J
通讯作者：
OQuigley, J