基于模型的Meta分析方法(1)

1、基于模型的Meta分析方法一个研究实例东方人？东方人？Dose (mg)LDL % change from base020406080-60-40-200AtorvastatinDose (mg)LDL % change from base020406080-60-40-200SimvastatinDose (mg)LDL % change from base020406080-60-40-200RosuvastatinDose (mg)LDL % change from base020406080-60-40-200PravastatinDose (mg)LDL % change from

2、base020406080-60-40-200LovastatinDose (mg)LDL % change from base010203040-60-40-200Ezetimibe东方人？亚裔比西方人群亚裔比西方人群清除率清除率CLCL小小2 2倍倍, , 东方人用量？东方人用量？ 基于文献均数(标准差)数据，建立群体药效学模型，评价瑞舒伐他汀在东西方高血酯人群的降LDL-C作用，比较种族差异 多剂量随机对照临床试验的检索流程050maxEDoseEDDoseEEiiTVPP)(iiEXPTVPP)1 (iiTVPP)(EXPYYpredobspredobsYY)1 (predobsYY0

3、50maxEDoseEDDoseEE EYobsMean数据集，再根据文献固定gamma和E0个体典型数据集TVP, typical population parameter value. SE, standard error. RSE, relative standard error, calculated as SE/TVP and expressed as a percentage. 95% CI, lower and upper limits of the 95% confidence interval, calculated as parameter estimates 1.96 S

4、E. Interindividual variability was expressed as percentage coefficient of variation (CV) and was calculated by taking the square root of (the variance associated with the parameter values) and multiplying by 100. Residual error was expressed as standard deviation. 典型个体化数据集的群体药效学参数 亚裔人群(右)与西方人群(左)的量效

5、曲线与数据数据Red round, individual observed effect in Western patients; black triangle, individual observed effect in Asian patients; red curve, the model-predicted dose-response curve in Western patients; black curve, the model-predicted dose-response curve in Asian patients.亚裔人群(黑)与西方人群(红)的对数剂量与LDL-C下降率

6、曲线Red curve, LDL-C% change in Western patients; Black curve, LDL-C% change in Asian patients; Vertical dash line, rosuvastatin 11 mg; Horizontal dash line, 48% reduction in LDL-C. 西方人群的建模数据的拟合优度(A) Scatter plot of population model-predicted effects (PRED) versus observed effects (OBS). (B) Scatter p

7、lot individual model-predicted effects (IPRED) versus OBS. The solid line is the linear of identity. (C) Plot of weighted residuals (WRES) versus PRED. (D) Plot of WRES versus the patients identification number (ID). ABCD亚裔人群的建模数据的拟合优度 (A) Scatter plot of population model-predicted effects (PRED) ve

8、rsus observed effects (OBS). (B) Scatter plot individual model-predicted effects (IPRED) versus OBS. The solid line is the linear of identity. (C) Plot of weighted residuals (WRES) versus PRED. (D) Plot of WRES versus the patients identification number (ID).ABCD西方人群西方人群(A)和亚裔人群（和亚裔人群（B）的剂量）的剂量-用药时间用

9、药时间-疗效疗效关系关系The response is improved with the increase in dose, but it is maintained at different time after 4 weeks during chronic therapy. AB不同数据集与子集中Emax, ED50, 和 E0的群体值（典型值）The solid and broken lines are the parameter value and 1.96 SE values from the total data set, respectively. 22个验证试验的PRED和真值间的预测误差 (Pe, %)