Precision medicine, aka stratified/personalized medicine, is becoming more pronounced in the medical field due to advancement in computational ability to learn about patient genomic backgrounds. A biomaker, i.e. a type of biological process indicator, is often used in precision medicine to classify patient population into several subgroups. The aim of precision medicine is to tailor treatment regimes for different patient subgroups who suffer from the same disease. A multi-arm design could be conducted to explore the effect of treatment regimes on different biomarker subgroups. However, if treatments work only on certain subgroups, which is often the case, enrolling all patient subgroups in a confirmatory trial would increase the burden of a study. Having observed a phase II trial, we propose a design framework for finding an optimal design that could be implemented in a phase III study or a confirmatory trial. We consider two elements in our approach: Bayesian data analysis of observed data, and design of experiments. The first tool selects subgroups and treatments to be enrolled in the future trial whereas the second tool provides an optimal treatment randomization scheme for each selected/enrolled subgroups. Considering two independent treatments and two independent biomarkers, we illustrate our approach using simulation studies. We demonstrate efficiency gain, i.e. high probability of recommending truly effective treatments in the right subgroup, of the optimal design found by our framework over a randomized controlled trial and a biomarker–treatment linked trial.

中文翻译：

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精准医学验证性试验的实验设计

由于了解患者基因组背景的计算能力的进步，精准医学，又名分层/个性化医学，在医学领域变得越来越明显。生物制造商，即一种生物过程指标，常用于精准医学，将患者群体分为几个亚组。精准医学的目标是为患有相同疾病的不同患者亚组量身定制治疗方案。可以进行多臂设计来探索治疗方案对不同生物标志物亚组的影响。然而，如果治疗仅对某些亚组有效（通常是这种情况），则将所有患者亚组纳入验证性试验会增加研究负担。在观察了 II 期试验后，我们提出了一个设计框架，用于寻找可在 III 期研究或验证性试验中实施的最佳设计。我们在我们的方法中考虑了两个要素：观察数据的贝叶斯数据分析和实验设计。第一个工具选择在未来试验中登记的亚组和治疗，而第二个工具为每个选定/登记的亚组提供最佳治疗随机化方案。考虑到两个独立的治疗和两个独立的生物标志物，我们使用模拟研究来说明我们的方法。我们证明了我们的框架在随机对照试验和生物标志物-治疗相关试验中发现的最佳设计的效率增益，即在正确的亚组中推荐真正有效的治疗的可能性很高。