Keyboard: A Novel Bayesian Toxicity Probability Interval Design for Phase I Clinical Trials.
Keyboard: A Novel Bayesian Toxicity Probability Interval Design for Phase I Clinical Trials.
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DOI：
10.1158/1078-0432.ccr-17-0220
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Yuan Y
中科院分区：
文献类型：
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作者：
Yan F;Mandrekar SJ;Yuan Y
I 期肿瘤学试验的主要目标是找到最大耐受剂量 (MTD)。 3+3设计很容易实现，但在寻找MTD方面表现不佳。更新的设计，例如修改后的毒性概率区间 (mTPI) 设计，可以提供更好的准确度来识别 MTD，但往往会使患者服用过量。我们提出了键盘设计，这是一种直观的贝叶斯设计，根据最强的键（定义为最有可能包含当前剂量的给药间隔）是否低于或高于目标给药间隔来进行剂量递增和递减。键盘设计可以以简单的方式实现，类似于传统的3+3设计，但为选择目标毒性率和队列大小提供了更大的灵活性。我们的模拟研究表明，与 3+3 设计相比，键盘设计在识别 MTD 方面具有良好的操作特性。与mTPI设计相比，键盘设计更安全，以过量毒性剂量治疗患者的风险大大降低，并且具有更好的MTD识别精度，从而为mTPI设计提供了有用的升级。 http://www.Trialdesign.org 上免费提供的软件促进了键盘设计的应用。
The primary objective of phase I oncology trials is to find the maximum tolerated dose (MTD). The 3+3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval. The keyboard design can be implemented in a simple way, similar to the traditional 3+3 design, but provides more flexibility for choosing the target toxicity rate and cohort size. Our simulation studies demonstrate that compared to the 3+3 design, the keyboard design has favorable operating characteristics in terms of identifying the MTD. Compared to the mTPI design, the keyboard design is safer, with a substantially lower risk of treating patients at overly toxic doses, and has the better precision to identify the MTD, thereby providing a useful upgrade to the mTPI design. Software freely available at http://www.trialdesign.org facilitates the application of the keyboard design.