Liu Suyu, Pan Haitao, Xia Jielai, Huang Qin, Yuan Ying
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, U.S.A.
Stat Med. 2015 May 10;34(10):1681-94. doi: 10.1002/sim.6442. Epub 2015 Jan 28.
Accumulating evidence shows that the conventional one-size-fits-all dose-finding paradigm is problematic when applied to different ethnic populations. Because of inter-ethnic heterogeneity, the dosage established in a landmark trial for a certain population may not be generalizable to a different ethnic population, and a follow-up bridge trial is often needed to find the maximum tolerated dose for the new population. We propose the bridging continual reassessment method (B-CRM) to facilitate dose finding for such follow-up bridge trials. The B-CRM borrows information from the landmark trial through a novel estimate of the dose-toxicity curve and accommodates the inter-ethnic heterogeneity using the Bayesian model averaging approach. Extensive simulation studies show that the B-CRM has desirable operating characteristics with a high probability to select the target dose. This article focuses on ethnic heterogeneity, but the proposed method can be directly used to handle other types of patient heterogeneity, for example, patient subgroups defined by prognostic factors or biomarkers. The software to implement the B-CRM design is available for free download at http://odin.mdacc.tmc.edu/~yyuan/.
越来越多的证据表明，传统的一刀切剂量寻找模式应用于不同种族人群时存在问题。由于种族间的异质性，在一项针对特定人群的标志性试验中确定的剂量可能无法推广到不同的种族人群，通常需要进行后续的桥接试验来找到新人群的最大耐受剂量。我们提出了桥接连续重新评估方法（B-CRM），以促进此类后续桥接试验的剂量寻找。B-CRM通过对剂量-毒性曲线的新颖估计从标志性试验中获取信息，并使用贝叶斯模型平均方法来适应种族间的异质性。大量的模拟研究表明，B-CRM具有理想的操作特性，有很高的概率选择目标剂量。本文关注种族异质性，但所提出的方法可直接用于处理其他类型的患者异质性，例如，由预后因素或生物标志物定义的患者亚组。实施B-CRM设计的软件可从http://odin.mdacc.tmc.edu/~yyuan/免费下载。
