BAYESIAN PHASE I/II ADAPTIVELY RANDOMIZED ONCOLOGY TRIALS WITH COMBINED DRUGS.
BAYESIAN PHASE I/II ADAPTIVELY RANDOMIZED ONCOLOGY TRIALS WITH COMBINED DRUGS.
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DOI：
10.1214/10-aoas433
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发表时间：
2011-01-01
期刊：
影响因子：
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通讯作者：
Yin G
中科院分区：
文献类型：
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作者：
Yuan Y;Yin G
我们提出了一个新的综合I/II期试验设计，以确定最有效的剂量组合，同时满足药物联合试验的某些安全性要求。在确定了一组可接受的剂量后，我们立即将整个剂量集向前推进到第二阶段。我们提出了一种新的自适应随机化方案，有利于将患者分配到更有效的剂量联合组。我们的自适应随机化方案考虑了疗效的点估计和可变性。我们的方法通过移动参照物比较不同治疗组的相对疗效，达到了区分不同治疗组的高分辨率。当疗效迟发时，我们也考虑分组自适应随机化。我们进行了广泛的模拟研究，以检查拟议设计的操作特性，并使用I/II期黑色素瘤临床试验说明我们的方法。
We propose a new integrated phase I/II trial design to identify the most efficacious dose combination that also satisfies certain safety requirements for drug-combination trials. We first take a Bayesian copula-type model for dose finding in phase I. After identifying a set of admissible doses, we immediately move the entire set forward to phase II. We propose a novel adaptive randomization scheme to favor assigning patients to more efficacious dose-combination arms. Our adaptive randomization scheme takes into account both the point estimate and variability of efficacy. By using a moving reference to compare the relative efficacy among treatment arms, our method achieves a high resolution to distinguish different arms. We also consider groupwise adaptive randomization when efficacy is late-onset. We conduct extensive simulation studies to examine the operating characteristics of the proposed design, and illustrate our method using a phase I/II melanoma clinical trial.