~~~ This report is generated using bear v2.2.0 for R. ~~~ Authors: Hsin-ya Lee, Yung-jin Lee College of Pharmacy, Kaohsiung Medical University Kaohsiung, Taiwan 80708 E-mail: hsinyalee@gmail.com,pkpd.taiwan@gmail.com bear's website: http://pkpd.kmu.edu.tw/bear R website: http://www.r-project.org --------------------------------------------------- *** This is a 2-treatment, 2-sequence, 4 periods replicated design. -------------------------------------------------------------------------- Statistical analysis (lme, 90%CI...) - replicate BE study -------------------------------------------------------------------------- Dependent Variable: Cmax Linear mixed-effects model fit by REML Data: TotalData AIC BIC logLik 691.518 706.8141 -337.759 Random effects: Formula: ~1 | subj (Intercept) Residual StdDev: 127.4921 150.7802 Fixed effects: Cmax ~ seq + prd + drug Value Std.Error DF t-value p-value (Intercept) 1600.4643 68.97748 38 23.202708 0.0000 seq2 -8.3929 79.17054 12 -0.106010 0.9173 prd2 -95.0000 56.98957 38 -1.666972 0.1037 prd3 24.2857 56.98957 38 0.426143 0.6724 prd4 44.2143 56.98957 38 0.775831 0.4427 drug2 72.8929 40.29771 38 1.808858 0.0784 Correlation: (Intr) seq2 prd2 prd3 prd4 seq2 -0.574 prd2 -0.413 0.000 prd3 -0.413 0.000 0.500 prd4 -0.413 0.000 0.500 0.500 drug2 -0.292 0.000 0.000 0.000 0.000 Standardized Within-Group Residuals: Min Q1 Med Q3 Max -1.6532258 -0.6285768 0.1169075 0.5716230 1.5865486 Number of Observations: 56 Number of Groups: 14 Type I Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 1687.4137 <.0001 seq 1 12 0.0112 0.9173 prd 3 38 2.3388 0.0888 drug 1 38 3.2720 0.0784 Type III Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 538.3656 <.0001 seq 1 12 0.0112 0.9173 prd 3 38 2.3388 0.0888 drug 1 38 3.2720 0.0784 Statistical analysis (lme, 90%CI...) - replicate BE study -------------------------------------------------------------------------- Dependent Variable: AUC0t Linear mixed-effects model fit by REML Data: TotalData AIC BIC logLik 930.9227 946.2189 -457.4614 Random effects: Formula: ~1 | subj (Intercept) Residual StdDev: 1022.716 1752.486 Fixed effects: AUC0t ~ seq + prd + drug Value Std.Error DF t-value p-value (Intercept) 13877.490 691.7219 38 20.062239 0.0000 seq2 -662.032 719.8709 12 -0.919653 0.3759 prd2 -547.861 662.3776 38 -0.827112 0.4133 prd3 -715.498 662.3776 38 -1.080197 0.2869 prd4 -422.642 662.3776 38 -0.638068 0.5273 drug2 617.552 468.3717 38 1.318509 0.1952 Correlation: (Intr) seq2 prd2 prd3 prd4 seq2 -0.520 prd2 -0.479 0.000 prd3 -0.479 0.000 0.500 prd4 -0.479 0.000 0.500 0.500 drug2 -0.339 0.000 0.000 0.000 0.000 Standardized Within-Group Residuals: Min Q1 Med Q3 Max -1.8897926 -0.7978567 0.2192397 0.7491229 1.4197235 Number of Observations: 56 Number of Groups: 14 Type I Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 1392.9810 <.0001 seq 1 12 0.8458 0.3759 prd 3 38 0.4256 0.7358 drug 1 38 1.7385 0.1952 Type III Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 402.4935 <.0001 seq 1 12 0.8458 0.3759 prd 3 38 0.4256 0.7358 drug 1 38 1.7385 0.1952 Statistical analysis (lme, 90%CI...) - replicate BE study -------------------------------------------------------------------------- Dependent Variable: AUC0INF Linear mixed-effects model fit by REML Data: TotalData AIC BIC logLik 938.887 954.1831 -461.4435 Random effects: Formula: ~1 | subj (Intercept) Residual StdDev: 1151.706 1885.607 Fixed effects: AUC0INF ~ seq + prd + drug Value Std.Error DF t-value p-value (Intercept) 14542.311 755.2730 38 19.254376 0.0000 seq2 -779.663 795.5779 12 -0.979996 0.3464 prd2 -617.859 712.6925 38 -0.866937 0.3914 prd3 -672.683 712.6925 38 -0.943862 0.3512 prd4 -434.220 712.6925 38 -0.609267 0.5460 drug2 758.049 503.9497 38 1.504215 0.1408 Correlation: (Intr) seq2 prd2 prd3 prd4 seq2 -0.527 prd2 -0.472 0.000 prd3 -0.472 0.000 0.500 prd4 -0.472 0.000 0.500 0.500 drug2 -0.334 0.000 0.000 0.000 0.000 Standardized Within-Group Residuals: Min Q1 Med Q3 Max -1.9258470 -0.7416279 0.1124585 0.7392567 2.1440118 Number of Observations: 56 Number of Groups: 14 Type I Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 1256.4699 <.0001 seq 1 12 0.9604 0.3464 prd 3 38 0.3663 0.7777 drug 1 38 2.2627 0.1408 Type III Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 370.7310 <.0001 seq 1 12 0.9604 0.3464 prd 3 38 0.3663 0.7777 drug 1 38 2.2627 0.1408 Statistical analysis (lme, 90%CI...) - replicate BE study -------------------------------------------------------------------------- Dependent Variable: lnCmax Linear mixed-effects model fit by REML Data: TotalData AIC BIC logLik -45.23532 -29.93913 30.61766 Random effects: Formula: ~1 | subj (Intercept) Residual StdDev: 0.07591504 0.096394 Fixed effects: lnCmax ~ seq + prd + drug Value Std.Error DF t-value p-value (Intercept) 7.372429 0.04264797 38 172.86705 0.0000 seq2 -0.009494 0.04806556 12 -0.19753 0.8467 prd2 -0.062443 0.03643351 38 -1.71389 0.0947 prd3 0.017159 0.03643351 38 0.47097 0.6404 prd4 0.027577 0.03643351 38 0.75691 0.4538 drug2 0.046554 0.02576238 38 1.80705 0.0787 Correlation: (Intr) seq2 prd2 prd3 prd4 seq2 -0.564 prd2 -0.427 0.000 prd3 -0.427 0.000 0.500 prd4 -0.427 0.000 0.500 0.500 drug2 -0.302 0.000 0.000 0.000 0.000 Standardized Within-Group Residuals: Min Q1 Med Q3 Max -1.9923453 -0.4759801 0.1513995 0.5975501 1.5432336 Number of Observations: 56 Number of Groups: 14 Type I Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 94465.47 <.0001 seq 1 12 0.04 0.8467 prd 3 38 2.45 0.0785 drug 1 38 3.27 0.0787 Type III Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 29883.017 <.0001 seq 1 12 0.039 0.8467 prd 3 38 2.449 0.0785 drug 1 38 3.265 0.0787 Statistical analysis (lme, 90%CI...) - replicate BE study -------------------------------------------------------------------------- Dependent Variable: lnAUC0t Linear mixed-effects model fit by REML Data: TotalData AIC BIC logLik -14.86023 0.4359588 15.43011 Random effects: Formula: ~1 | subj (Intercept) Residual StdDev: 0.07370342 0.1385176 Fixed effects: lnAUC0t ~ seq + prd + drug Value Std.Error DF t-value p-value (Intercept) 9.531564 0.05321458 38 179.11563 0.0000 seq2 -0.050964 0.05406075 12 -0.94272 0.3644 prd2 -0.048913 0.05235474 38 -0.93425 0.3561 prd3 -0.063764 0.05235474 38 -1.21792 0.2308 prd4 -0.030452 0.05235474 38 -0.58164 0.5642 drug2 0.047598 0.03702039 38 1.28572 0.2063 Correlation: (Intr) seq2 prd2 prd3 prd4 seq2 -0.508 prd2 -0.492 0.000 prd3 -0.492 0.000 0.500 prd4 -0.492 0.000 0.500 0.500 drug2 -0.348 0.000 0.000 0.000 0.000 Standardized Within-Group Residuals: Min Q1 Med Q3 Max -1.9793253 -0.7502783 0.2145861 0.7287320 1.2553565 Number of Observations: 56 Number of Groups: 14 Type I Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 123368.22 <.0001 seq 1 12 0.89 0.3644 prd 3 38 0.55 0.6508 drug 1 38 1.65 0.2063 Type III Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 32082.41 <.0001 seq 1 12 0.89 0.3644 prd 3 38 0.55 0.6508 drug 1 38 1.65 0.2063 Statistical analysis (lme, 90%CI...) - replicate BE study -------------------------------------------------------------------------- Dependent Variable: lnAUC0INF Linear mixed-effects model fit by REML Data: TotalData AIC BIC logLik -13.45392 1.842261 14.72696 Random effects: Formula: ~1 | subj (Intercept) Residual StdDev: 0.07629541 0.140054 Fixed effects: lnAUC0INF ~ seq + prd + drug Value Std.Error DF t-value p-value (Intercept) 9.578387 0.05415894 38 176.85699 0.0000 seq2 -0.055088 0.05535540 12 -0.99516 0.3393 prd2 -0.052085 0.05293544 38 -0.98393 0.3314 prd3 -0.061600 0.05293544 38 -1.16368 0.2518 prd4 -0.029772 0.05293544 38 -0.56241 0.5771 drug2 0.053863 0.03743101 38 1.43899 0.1583 Correlation: (Intr) seq2 prd2 prd3 prd4 seq2 -0.511 prd2 -0.489 0.000 prd3 -0.489 0.000 0.500 prd4 -0.489 0.000 0.500 0.500 drug2 -0.346 0.000 0.000 0.000 0.000 Standardized Within-Group Residuals: Min Q1 Med Q3 Max -2.0231739 -0.7135015 0.1297203 0.7320386 1.7805744 Number of Observations: 56 Number of Groups: 14 Type I Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 118853.14 <.0001 seq 1 12 0.99 0.3393 prd 3 38 0.54 0.6611 drug 1 38 2.07 0.1583 Type III Tests of Fixed Effects numDF denDF F-value p-value (Intercept) 1 38 31278.394 <.0001 seq 1 12 0.990 0.3393 prd 3 38 0.535 0.6611 drug 1 38 2.071 0.1583 BE Summary Report - replicate BE study -------------------------------------------------------------------------- Dependent Variable: lnCmax -------------------------------------------------------------------------- n1(seq 1)= 7 n2(seq 2)= 7 N(n1+n2) = 14 MEAN-ref = 7.363255 MEAN-test = 7.409809 Estimate(test-ref) = 0.04655381 **************** Classical (Shortest) 90% C.I. for lnCmax ***************** CI90_lower Point_estimated CI90_upper 1 100.312 104.765 109.416 -------------------------------------------------------------------------- BE Summary Report - replicate BE study -------------------------------------------------------------------------- Dependent Variable: lnAUC0t -------------------------------------------------------------------------- n1(seq 1)= 7 n2(seq 2)= 7 N(n1+n2) = 14 MEAN-ref = 9.4703 MEAN-test = 9.517898 Estimate(test-ref) = 0.04759799 **************** Classical (Shortest) 90% C.I. for lnAUC0t **************** CI90_lower Point_estimated CI90_upper 1 98.529 104.875 111.629 -------------------------------------------------------------------------- BE Summary Report - replicate BE study -------------------------------------------------------------------------- Dependent Variable: lnAUC0INF -------------------------------------------------------------------------- n1(seq 1)= 7 n2(seq 2)= 7 N(n1+n2) = 14 MEAN-ref = 9.514979 MEAN-test = 9.568842 Estimate(test-ref) = 0.05386282 **************** Classical (Shortest) 90% C.I. for lnAUC0INF ************** CI90_lower Point_estimated CI90_upper 1 99.080 105.534 112.409 --------------------------------------------------------------------------