基于阿基米德Copula回归模型双计数数据新药安全性有效性评价  

Dose finding based on count efficacy-toxicity response using Archimedean Copula

作　　者：凌佳[1] 王菲[2] 言方荣[2] LING Jia WANGFe YAN Fang-rong(Jiangsu Open University, Nanjing 210036, China Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanfing 210009, China)

机构地区：[1]江苏开放大学,南京210036 [2]中国药科大学理学院生物统计与计算药学研究中心,南京210009

出　　处：《中国新药杂志》2017年第3期265-270,共6页Chinese Journal of New Drugs

基　　金：国家社科基金一般项目(16BTJ021);江苏省高校自然科学研究项目(14KJD110001);江苏开放大学"十二五"规划课题资助项目(13SEW-Q-054);江苏省教育厅资助项目(2015SJD122)

摘　　要：目的:研究新药安全性指标和有效性指标为计数数据以及相关条件下的联合评价及剂量选择问题。方法:基于阿基米德Copula性质建立了双计数数据联合评价模型,并提出了联合概率法进行剂量选择。结果与结论:阿基米德Copula具有良好的效果。首先,可以方便地刻画变量间相关性。另外,安全性和有效性回归模型参数具有明显生理学意义。同时,阿基米德Copula对概率分布没有任何限制。模拟结果表明,阿基米德Copula联合模型可以很好地刻画具有相关性安全性有效性指标,同时选择最优给药剂量。Objective：To propose a new strategy for dose-finding in clinical trials when both efficacy and toxicity responses are count data with dependence. Methods：A bivariate count responses model was established using Archimedean Copula,and a dose decision rule was developed based on the joint probability of both efficacy and toxicity. Results and Conclusion：Significant gains can be achieved when using Archimedean Copula joint model. Firstly,the correlation between efficacy and toxicity can be estimated. Secondly,the regression parameters in Archimedean Copula for both efficacy and toxicity are meaningful. Thirdly,Archimedean Copula has no restrictions on the probability distribution of response. The simulation study showed that the new joint model based on Archimedean Copula can enable physicians to evaluate the efficacy and toxicity simultaneously and select the optimal dose successfully.

关 键 词：阿基米德COPULA 剂量发现 联合回归模型 计数数据 

分 类 号：R95[医药卫生—药学]