Chen Xin, Zhang Jingyi, Jiang Qian, Yan Fangrong
Department of Biostatistics, China Pharmaceutical University, Nanjing, Jiangsu, China.
J Biopharm Stat. 2022 Jan 2;32(1):34-52. doi: 10.1080/10543406.2022.2058526. Epub 2022 May 20.
Multiple phase I clinical trials may be performed to determine specific maximum tolerated doses (MTD) for specific races or cancer types. In these situations, borrowing historical information has potential to improve the accuracy of estimating toxicity rate and increase the probability of correctly targeting MTD. To utilize historical information in phase I clinical trials, we proposed using the Meta-Analytic-Predictive (MAP) priors to automatically estimate the heterogeneity between historical trials and give a relatively reasonable amount of borrowed information. We then applied MAP priors in some famous phase I trial designs, such as the continual reassessment method (CRM), Keyboard design and Bayesian optimal interval design (BOIN), to accomplish the process of dose finding. A clinical trial example and extended simulation studies show that our proposed methods have robust and efficient statistical performance, compared with those designs which do not consider borrowing information.
可能会进行多项I期临床试验,以确定特定种族或癌症类型的特定最大耐受剂量(MTD)。在这些情况下,借鉴历史信息有可能提高毒性率估计的准确性,并增加正确靶向MTD的概率。为了在I期临床试验中利用历史信息,我们建议使用荟萃分析预测(MAP)先验来自动估计历史试验之间的异质性,并给出相对合理的借鉴信息量。然后,我们将MAP先验应用于一些著名的I期试验设计,如连续重新评估法(CRM)、键盘设计和贝叶斯最优区间设计(BOIN),以完成剂量探索过程。一个临床试验实例和扩展模拟研究表明,与那些不考虑借鉴信息的设计相比,我们提出的方法具有稳健且高效的统计性能。