Stallard Nigel, Rosenberger William F
Medical and Pharmaceutical Statistics Research Unit, The University of Reading, P.O. Box 240, Earley Gate, Reading RG6 6FN, UK.
Stat Med. 2002 Feb 28;21(4):467-80. doi: 10.1002/sim.998.
The use of both sequential designs and adaptive treatment allocation are effective in reducing the number of patients receiving an inferior treatment in a clinical trial. In large samples, when the asymptotic normality of test statistics can be utilized, a standard sequential design can be combined with adaptive allocation. In small samples the planned error rate constraints may not be satisfied if normality is assumed. We address this problem by constructing sequential stopping rules with specified properties by consideration of the exact distribution of test statistics under a particular adaptive allocation scheme, the randomized play-the-winner rule. Using this approach, compared to traditional equal allocation trials, trials with adaptive allocation are shown to require a larger total sample size to achieve a given power. More interestingly, the expected number patients allocated to the inferior treatment may also be larger for the adaptive allocation designs depending on the true success rates.
序贯设计和适应性治疗分配的使用在减少临床试验中接受较差治疗的患者数量方面是有效的。在大样本中，当可以利用检验统计量的渐近正态性时，标准序贯设计可以与适应性分配相结合。在小样本中，如果假定正态性，计划的错误率约束可能无法满足。我们通过考虑特定适应性分配方案（随机胜者优先规则）下检验统计量的精确分布，构建具有特定属性的序贯停止规则来解决这个问题。使用这种方法，与传统的均等分配试验相比，适应性分配试验显示需要更大的总样本量才能达到给定的检验效能。更有趣的是，根据真实成功率，适应性分配设计中分配到较差治疗的预期患者数量也可能更多。
