Outcome-Adaptive Randomization: Is It Useful?
Outcome-Adaptive Randomization: Is It Useful?
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DOI：
10.1200/jco.2010.31.1423
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发表时间：
2011-02-20
影响因子：
45.3
通讯作者：
Freidlin, Boris
中科院分区：
文献类型：
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作者：
Korn, Edward L.;Freidlin, Boris
结果适应性随机化是适应性试验设计的可能要素之一，其中随机分配到实验治疗组与对照治疗组的患者比例随着时间的推移从1：1变为随机分配更高比例的患者到表现更好的组。结果适应性随机化具有直观的吸引力，因为平均而言，更高比例的患者将接受更好的治疗组（如果有）。在具有短期二元结局的随机II期和III期研究中，我们将结局适应性随机化与使用1：1和2：1固定比例随机化的设计进行了比较（在后者中，随机分配到实验治疗组的患者数量是后者的两倍）。根据所需的样本量、结局较差的患者数量和比例进行比较，我们将注意力限制在一个治疗组为对照治疗的情况下（而不是不太常见的两种实验治疗无对照治疗的情况）。由于试验设计的原因，患者入组率没有差异，我们发现结果适应性随机化与1：1随机化相比没有任何益处，我们推荐后者。如果认为患者入组率会因更高比例的患者可能被随机分配至试验治疗而显著更高（因为试验对患者和临床医生更具吸引力），我们建议使用固定的2：1随机化，而不是结局适应性随机化。
Outcome-adaptive randomization is one of the possible elements of an adaptive trial design in which the ratio of patients randomly assigned to the experimental treatment arm versus the control treatment arm changes from 1: 1 over time to randomly assigning a higher proportion of patients to the arm that is doing better. Outcome-adaptive randomization has intuitive appeal in that, on average, a higher proportion of patients will be treated on the better treatment arm (if there is one). In both the randomized phase II and phase III settings with a short-term binary outcome, we compare outcome-adaptive randomization with designs that use 1: 1 and 2: 1 fixed-ratio randomizations (in the latter, twice as many patients are randomly assigned to the experimental treatment arm). The comparisons are done in terms of required sample sizes, the numbers and proportions of patients having an inferior outcome, and we restrict attention to the situation in which one treatment arm is a control treatment (rather than the less common situation of two experimental treatments without a control treatment). With no differential patient accrual rates because of the trial design, we find no benefits to outcome-adaptive randomization over 1: 1 randomization, and we recommend the latter. If it is thought that the patient accrual rates will be substantially higher because of the possibility of a higher proportion of patients being randomly assigned to the experimental treatment (because the trial will be more attractive to patients and clinicians), we recommend using a fixed 2: 1 randomization instead of an outcome-adaptive randomization.