Bayesian optimal phaseIIclinical trial design with time-to-event endpoint
Bayesian optimal phaseIIclinical trial design with time-to-event endpoint
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DOI：
10.1002/pst.2030
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发表时间：
2020-06-10
影响因子：
1.5
通讯作者：
Yuan, Ying
中科院分区：
文献类型：
--
作者：
Zhou, Heng;Chen, Cong;Yuan, Ying
我们提出了一种贝叶斯最优II期（BOP 2）设计，用于具有至事件发生时间终点（例如，无进展生存期[PFS]）或由至事件发生时间终点和分类终点（例如，PFS和毒性）组成的协同主要终点的临床试验。我们使用一个指数-逆伽马模型来模拟事件发生的时间。在每个中期，通过将感兴趣事件的后验概率与自适应概率截止值进行比较来做出进行/不进行决策。BOP 2设计在中期外观数量方面具有灵活性，适用于单组和双组试验。该设计最大限度地提高了检测有效治疗的功效，并具有良好控制的I型错误，从而弥合了贝叶斯设计和频率论设计之间的差距。BOP 2设计易于实现。对于单组研究，可在试验开始前列举其停止边界并纳入研究方案中。模拟研究表明，BOP 2设计具有良好的操作特性，与一些贝叶斯第二阶段设计相比，具有更高的功率和更低的错误终止试验的风险。用于实现BOP 2设计的软件将免费提供。
We propose a Bayesian optimal phase II (BOP2) design for clinical trials with a time-to-event endpoint (eg, progression-free survival [PFS]) or co-primary endpoints consisted of a time-to-event endpoint and a categorical endpoint (eg, PFS and toxicity). We use an exponential-inverse gamma model to model the time to event. At each interim, the go/no-go decision is made by comparing the posterior probabilities of the event of interest with an adaptive probability cutoff. The BOP2 design is flexible in the number of interim looks and applicable to both single-arm and two-arm trials. The design maximizes the power for detecting effective treatments, with a well-controlled type I error, thereby bridging the gap between Bayesian designs and frequentist designs. The BOP2 design is easy to implement. Its stopping boundary can be enumerated and included in study protocol before the onset of the trial for single-arm studies. Simulation studies show that the BOP2 design has favorable operating characteristics, with higher power and lower risk of incorrectly terminating the trial than some Bayesian phase II designs. The software to implement the BOP2 design will be freely available at .