检验新疗法对比标准疗法有效性的大多数肿瘤学随机研究为双组研究，从而将许多患者分配接受对照疗法。相比之下，多个研究组有效共享同一对照组，可以同时评价多个新疗法。传统多组研究的主要瓶颈在于要求所有疗法（通常来自不同公司的药物）必须在研究开始同时进行。
2017年5月22日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表罗德岛大学、达纳法伯癌症研究所、哈佛大学医学院、哈佛大学陈曾熙公共卫生学院、前沿科学基金会的研究报告，评价了平台设计（滚动入组设计）在滚动基础上增加和移除分组的潜在收益。
本研究定义了最小化平台研究随机分配和数据分析复杂性的滚动入组设计，然后评价了其对激素受体阳性HER2阴性晚期乳腺癌的潜在优势。目前，多家制药公司正在独立的双组研究中检验CDK4/6抑制剂联合来曲唑。如果这些疗法在滚动入组研究中进行了检验，那么本研究对此进行模拟，以量化减少样本数、标准疗法患者数、治疗探索平均时间。
结果发现，与标准双组研究相比，2～5个新疗法的滚动平台设计可将总样本数需求量减少达30%。与检验不同治疗的5项独立研究相比，分配进入对照组的患者减少达60%。此外，在实际情况下，与单独的双组研究相比，有效新疗法的发现可被提前达15个月。
因此，滚动平台设计适用于各种疾病，在现实情况下，比标准双组随机研究更有效。
不过，滚动组设计的局限性之一在于其假设研究期间对照组治疗不变。在许多情况下，一旦新疗法取代目前标准疗法，就有必要停止临床研究，以大大改善总生存或减少不良反应。在某些情况下，正在进行的平台研究可能倾向于继续研究，并用新疗法取代对照组治疗，或者（如果可能且合适）继续使用旧的标准疗法。这些决策将取决于研究特定因素和新旧标准疗法的效果，需要根据持续平台研究期间标准疗法变化对滚动组设计进行必要的调整。
J Clin Oncol. 2017 May 22. [Epub ahead of print]
Designing Clinical Trials That Accept New Arms: An Example in Metastatic Breast Cancer.
Steffen Ventz, Brian M. Alexander, Giovanni Parmigiani, Richard D. Gelber, Lorenzo Trippa.
University of Rhode Island, Kingstown, RI; Dana-Farber Cancer Institute; Harvard Medical School; Harvard TH Chan School of Public Health; Frontier Science Foundation, Boston, MA.
PURPOSE: The majority of randomized oncology trials are two-arm studies that test the efficacy of new therapies against a standard of care, thereby assigning a large proportion of patients to nonexperimental therapies. In contrast, multiarm studies efficiently share a common control arm while evaluating multiple experimental therapies. A major bottleneck for traditional multiarm trials is the requirement that all therapies—often drugs from different companies—have to be available at the same time when the trial starts. We evaluate the potential gains of a platform design—the rolling-arms design—that adds and removes arms on a rolling basis.
METHODS: We define the rolling-arms design with the goal of minimizing the complexity of random assignment and data analyses of a platform trial. We then evaluate its potential advantages in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Multiple pharmaceutical companies currently test CDK4/6 inhibitors in combination with letrozole in independent two-arm trials. We conducted a simulation study to quantify the reduction in sample size, number of patients treated with the standard of care, and the average time to treatment discovery if these therapies had been tested in a rolling-arms trial.
RESULTS: A rolling-arms platform design with two to five experimental treatments can reduce the overall sample size requirement by up to 30% compared with standard two-arm studies. It assigns up to 60% fewer patients to the control arm compared with five independent trials that test distinct treatments. Moreover, under realistic scenarios, effective experimental treatments are discovered up to 15 months earlier compared with separate two-arm trials.
CONCLUSION: The rolling-arms platform design is applicable to a broad variety of diseases, and under realistic scenarios, it is substantially more efficient than standard two-arm randomized trials.
DOI: 10.1200/JCO.2016.70.1169
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