Massey Cancer Center and Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Clin Cancer Res. 2011 Sep 1;17(17):5538-45. doi: 10.1158/1078-0432.CCR-10-2466. Epub 2011 Jul 7.
Classical phase II trial designs, including "adaptive" designs, require the prospective characterization of tumors. We propose a 2-stage phase II design that allows for characterization of tumors and selection of a tumor subtype of interest at the conclusion of stage 1. The stage 2 objective is either a classical estimate of the response rate for either the tumor or a subtype, or a formal test of the hypothesis that the response rate for a subtype is greater than the overall response rate. Considering likely scenarios, stage 1 sample sizes approximately range from 20 to 100 with a usual size of 50. This compares with typical classical stage 1 sample sizes of 12 to 30. Total sample sizes range from sizes identical to classical designs (tens to scores) to large sizes typical of phase III trials in metastatic disease (hundreds). Our design is more efficient than previous adaptive designs because it allows for the selection of a tumor subtype of interest on the basis of results from stage 1. It complements classical phase II and phase III designs in which investigators compare different treatments in similar patients and tumors by positioning a treatment as fixed (control) and using tumor subtype as the variable of interest.
经典的 II 期临床试验设计，包括“适应性”设计，需要对肿瘤进行前瞻性特征描述。我们提出了一种两阶段 II 期设计，允许在第一阶段结束时对肿瘤进行特征描述，并选择感兴趣的肿瘤亚组。第二阶段的目标是对肿瘤或亚组的反应率进行经典估计，或者对亚组的反应率是否大于总体反应率的假设进行正式检验。考虑到可能的情况，第一阶段的样本量大约在 20 到 100 之间，通常为 50。这与典型的经典第一阶段样本量（12 到 30）相比。总样本量从与经典设计相同的数量（数十到数十）到转移性疾病中 III 期试验的典型大数量（数百）不等。我们的设计比以前的适应性设计更有效，因为它允许根据第一阶段的结果选择感兴趣的肿瘤亚组。它通过将治疗方法固定（对照）并将肿瘤亚组作为感兴趣的变量，补充了经典的 II 期和 III 期设计，在这些设计中，研究人员在相似的患者和肿瘤中比较不同的治疗方法。
