基于保序回归估计的最大耐受剂量确定方法  

The Method Based on the Isotonic Regression Estimation for Identifying the Maximum Tolerated Dose

作　　者：王雪丽[1,2] 张忠占[2] 陶剑[3] 史宁中[3] 

机构地区：[1]大庆石油学院数学系,大庆163318 [2]北京工业大学应用数理学院,北京100124 [3]东北师范大学数学与统计学院,长春130024

出　　处：《应用概率统计》2008年第5期522-530,共9页Chinese Journal of Applied Probability and Statistics

基　　金：国家自然科学基金(10371005);教育部优秀青年教师基金(VE00074);北京市优秀学术创新团队基金

摘　　要：I期临床试验研究的主要目标之一是评估药物在不同剂量水平下的毒性,并且建议一个对病人既安全又有效的剂量,即最大耐受剂量(MTD).本文针对拓展的up-and-down设计,进一步给出其基于保序回归估计的最大耐受剂量确定方法.经大量模拟,结果表明:基于保序回归估计的最大耐受剂量确定方法对推荐MTD的准确性和精确度,以及保护病人,防止病人暴露在较高毒性剂量水平下方面实现了有意义的改善.One of the primary objectives of a phase I study is to evaluate toxicity at different dose levels and recommend the maximum tolerated dose （MTD）. We give an extend up-and-down design method based on the isotonic regression estimation for identifying MTD. Through a lot of simulations, it shows that the design based on isotonic regression for identifying the maximum tolerated dose has improved the accuracy of recommending MTD. It apparently protects patients efficiently and prevents patients from excessive trials under the higher toxicity dose level and makes a great significance in phase I clinical trials design.

关 键 词：Ⅰ期临床试验 毒性研究 最大耐受剂量(MTD) 保序回归. 

分 类 号：O212[理学—概率论与数理统计]