论文标题
实用响应自适应块随机化(RABR)设计,具有I型错误保护
A practical Response Adaptive Block Randomization (RABR) design with analytic type I error protection
论文作者
论文摘要
从方法论,道德和务实的角度来看,反应自适应随机化(RAR)在受试者更有可能被随机分配给基于累积数据以更好地执行治疗组的意义上有吸引力。但是,RAR在具有多个活跃臂的验证性药物临床试验中的应用很大程度上是由于其复杂性,并且缺乏对不同治疗组的随机比率的控制。为了解决上述问题,我们提出了一个响应自适应块随机化(RABR)设计,允许任意预先指定的对照组和高性能组来满足临床试验目标。我们显示了RABR中常规未加权测试的有效性,其受控I型错误率基于样本量自适应设计的加权组合测试,无需大量样本近似。与流行的双重自适应偏见的硬币设计(DBCD)相比,拟议的RABR的优势在实现目标最终样本量方面,以满足监管要求和增加统计能力,并通过统计模拟和实用临床试验设计示例证明了统计能力。
Response adaptive randomization (RAR) is appealing from methodological, ethical, and pragmatic perspectives in the sense that subjects are more likely to be randomized to better performing treatment groups based on accumulating data. However, applications of RAR in confirmatory drug clinical trials with multiple active arms are limited largely due to its complexity, and lack of control of randomization ratios to different treatment groups. To address the aforementioned issues, we propose a Response Adaptive Block Randomization (RABR) design allowing arbitrarily pre-specified randomization ratios for the control and high-performing groups to meet clinical trial objectives. We show the validity of the conventional unweighted test in RABR with a controlled type I error rate based on the weighted combination test for sample size adaptive design invoking no large sample approximation. The advantages of the proposed RABR in terms of robustly reaching target final sample size to meet regulatory requirements and increasing statistical power as compared with the popular Doubly Adaptive Biased Coin Design (DBCD) are demonstrated by statistical simulations and a practical clinical trial design example.