Biometric Research Branch, EPN-8129, National Cancer Institute, Bethesda, MD 20892, USA.
J Clin Oncol. 2011 Feb 20;29(6):771-6. doi: 10.1200/JCO.2010.31.1423. Epub 2010 Dec 20.
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.
适应性随机分组是适应性试验设计的可能要素之一，在此设计中，患者随机分配至实验组和对照组的比例随时间从 1:1 变为随机分配给表现更好的组的患者比例更高。在具有短期二分类结局的随机二期和三期试验中，适应性随机分组具有直观吸引力，因为（如果存在）平均而言，更多的患者将接受更好的治疗（如果存在）。在具有短期二分类结局的随机二期和三期试验中，我们将适应性随机分组与使用 1:1 和 2:1 固定比例随机分组的设计进行比较（在后一种设计中，两倍数量的患者被随机分配至实验组）。我们根据所需样本量、具有较差结局的患者数量和比例进行比较，并将注意力限制在一个治疗组为对照组的情况（而不是较少见的没有对照组的两种实验组的情况）。由于试验设计，没有因患者入组率不同导致的差异，我们发现适应性随机分组与 1:1 随机分组相比没有优势，因此建议使用后者。如果由于更有可能将更多患者随机分配至实验组（因为试验对患者和临床医生更具吸引力）而认为患者入组率将大大提高，我们建议使用固定的 2:1 随机分组而不是适应性随机分组。
