A Phase I Bayesian Adaptive Design to Simultaneously Optimize Dose and Schedule Assignments Both Between and Within Patients.
A Phase I Bayesian Adaptive Design to Simultaneously Optimize Dose and Schedule Assignments Both Between and Within Patients.
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DOI：
10.1080/01621459.2013.806927
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发表时间：
2013-01-01
影响因子：
3.7
通讯作者：
Braun TM
中科院分区：
文献类型：
--
作者：
Zhang J;Braun TM
在传统的给药方案或剂量-给药方案探索设计中，假设患者在整个试验期间接受其分配的剂量-给药方案组合，即使发现该组合可能具有不良毒性特征，这与实际临床实践相矛盾。由于没有系统的方法来优化患者内的剂量-时间表分配，我们提出了一个I期临床试验设计，扩展了现有的方法，通过将适应性变化纳入患者内的剂量-时间表分配，以优化患者之间的剂量和时间表。我们的设计是基于贝叶斯非混合治愈率模型，该模型将每例患者接受的多次给药与每次给药剂量作为协变量。模拟表明，我们的设计确定安全的剂量和时间表组合以及传统的方法，不允许患者内剂量时间表重新分配，但有更多的患者分配到安全的组合。本文的补充材料可在网上查阅。
In traditional schedule or dose-schedule finding designs, patients are assumed to receive their assigned dose-schedule combination throughout the trial even though the combination may be found to have an undesirable toxicity profile, which contradicts actual clinical practice. Since no systematic approach exists to optimize intra-patient dose-schedule assignment, we propose a Phase I clinical trial design that extends existing approaches to optimize dose and schedule solely between patients by incorporating adaptive variations to dose-schedule assignments within patients as the study proceeds. Our design is based on a Bayesian non-mixture cure rate model that incorporates multiple administrations each patient receives with the per-administration dose included as a covariate. Simulations demonstrate that our design identifies safe dose and schedule combinations as well as the traditional method that does not allow for intra-patient dose-schedule reassignments, but with a larger number of patients assigned to safe combinations. Supplementary materials for this article are available online.
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影响因子：
1.9
作者：
Braun, TM;Yuan, Z;Thall, PF
通讯作者：
Thall, PF
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作者：
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通讯作者：
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