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Simulation Study for Evaluating the Performance of Response-Adaptive Randomization

机译:响应自适应随机性能评估的仿真研究

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摘要

A response-adaptive randomization (RAR) design refers to the method in which the probability of treatment assignment changes according to how well the treatments are performing in the trial. Holding the promise of treating more patients with the better treatments, RARs have been successfully implemented in clinical trials. We compared equal randomization (ER) with three RARs: Bayesian adaptive randomization, sequential maximum likelihood, and sequential posterior mean. We fixed the total number of patients, considering as patient horizon, but varied the number of patients in the trial. Among the designs, we compared the proportion of patients assigned to the superior arm, overall response rate, statistical power, and total patients enrolled in the trial if adding an efficacy early stopping rule. Without early stopping, ER is preferred when the number of patients beyond the trial is much larger than the number of patients in the trial. RAR is favored for large treatment difference or when the number of patients beyond the trial is small. With early stopping, the difference between these two types of designs was reduced. By carefully choosing the design parameters, both RAR and ER methods can achieve the desirable statistical properties. Within three RAR methods, we recommend SPM considering the larger proportion in the better arm and higher overall response rate than BAR and similar power and trial size with ER. The ultimate choice of RAR or ER methods depends on the investigator’s preference, the trade-off between group ethics and individual ethics, and logistic considerations in the trial conduct, etc.
机译:响应自适应随机(RAR)设计是指一种方法,其中,根据试验中治疗的执行情况,治疗分配的概率会发生变化。 RAR有望以更好的治疗方法治疗更多的患者,已在临床试验中成功实施。我们将相等随机数(ER)与三个RAR进行了比较:贝叶斯自适应随机数,顺序最大似然和顺序后验均值。我们确定了患者总数(考虑患者范围),但在试验中改变了患者数。在这些设计中,我们比较了上臂患者的比例,总体缓解率,统计学功效以及是否加入了有效的早期停药规则而参加了试验的患者总数。如果不尽早停止治疗,则当试验后的患者人数远大于试验中的患者人数时,首选ER。 RAR因治疗差异大或试验以外的患者人数少而受到青睐。通过提前停止,这两种设计之间的差异得以减小。通过仔细选择设计参数,RAR和ER方法均可达到理想的统计特性。在三种RAR方法中,我们建议SPM考虑比BAR更好的组中更大的比例和更高的总体响应率以及与ER相似的功效和试验规模。 RAR或ER方法的最终选择取决于研究者的偏爱,群体伦理与个人伦理之间的权衡以及审判行为中的后勤考虑等。

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