Piccorelli Annalisa V, Fraker Sarah A
a Department of Mathematics and Statistics , University of Wyoming , Laramie , WY , USA.
b Clinical Services Group , HCA Holdings, Inc ., Nashville , TN , USA.
J Biopharm Stat. 2018;28(6):1105-1118. doi: 10.1080/10543406.2018.1437172. Epub 2018 Feb 14.
During a clinical trial, balancing statistical and ethical considerations are important. Response-adaptive randomization methods use the information from past patients to increase the probability of the next patient receiving the better treatment while avoiding the statistical concern of selection bias. We compared three response-adaptive randomization urn designs, Randomized Play-the-Winner, Modified Play-the-Winner, and Birth-and-Death Urn with Immigration, to the traditional equal allocation design with respect to power and allocation of patients to the better treatment. Because these designs have been described separately, our motivation was to systematically compare them and provide recommendations. With simulations, we varied sample size and combinations of treatment and control success probabilities. We also compared the response-adaptive randomization designs using exact distribution algorithms and applied them to past clinical trial data that used an equal allocation design. We conclude that Modified Play-the-Winner tends to be unpredictable and can result in allocation of all of the patients to the better treatment. Randomized Play-the-Winner allocates more patients to the better treatment than Birth-and-Death Urn with Immigration, but Birth-and-Death Urn with Immigration is more consistent in its allocations. Randomized Play-the-Winner and Birth-and-Death Urn with Immigration produce allocations that have comparable powers to equal allocation design.
在临床试验中，平衡统计和伦理考量非常重要。响应自适应随机化方法利用过去患者的信息来提高下一位患者接受更好治疗的概率，同时避免选择偏倚的统计问题。我们将三种响应自适应随机化瓮设计，即随机胜者法、改进胜者法和带移民的生死瓮设计，与传统的均等分配设计在检验效能以及患者接受更好治疗的分配情况方面进行了比较。由于这些设计已分别进行过描述，我们的动机是对它们进行系统比较并提供建议。通过模拟，我们改变了样本量以及治疗组和对照组成功概率的组合。我们还使用精确分布算法比较了响应自适应随机化设计，并将它们应用于过去采用均等分配设计的临床试验数据。我们得出结论，改进胜者法往往不可预测，可能导致所有患者都被分配到更好的治疗组。随机胜者法比带移民的生死瓮设计将更多患者分配到更好的治疗组，但带移民的生死瓮设计在分配上更为一致。随机胜者法和带移民的生死瓮设计产生的分配在检验效能上与均等分配设计相当。
