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An average bioequivalence (ABE) and bioavailability data analysis tool including sample size estimation, noncompartmental analysis (NCA) for a standard RT / TR 2x2x2 crossover design or a parallel study. Package 'bear' May 28, 2010 Version 2.5.
An average bioequivalence (ABE) and bioavailability data analysis tool including sample size estimation, noncompartmental analysis (NCA) for a standard RT / TR 2x2x2 crossover design or a parallel study. Package 'bear' May 28, 2010 Version 2.5.
An average bioequivalence (ABE) and bioavailability data analysis tool including sample size estimation, noncompartmental analysis (NCA) for a standard RT / TR 2x2x2 crossover design or a parallel study. Package 'bear' May 28, 2010 Version 2.5.
Version 2.5.2 Date 2010-05-31 Title Average bioequivalence and bioavailability data analysis tool Author Hsin-ya Lee, Yung-jin Lee Maintainer Yung-jin Lee <mobilePK@gmail.com> Depends R (>= 2.10.0), reshape, nlme, sciplot, plotrix, ICSNP, gdata Description An average bioequivalence (ABE) and bioavailability data analysis tool including sample size estimation, noncompartmental analysis (NCA), ANOVA (lm) for a standard RT/TR 2x2x2 crossover design or a parallel study. And linear mixed effect model (lme of nlme) for a 2-treatment, 2-sequence with 2 periods or more (i.e. 2x2x3/2x2x4) replicate crossover design. License GPL (>= 2) URL http://pkpd.kmu.edu.tw/bear Repository CRAN Date/Publication 2010-05-28 06:55:45 R topics documented: aic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 AICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 AICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 AIC_BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 ARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 ARS.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 ARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 ARSdemo.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 ARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 BANOVAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 BANOVAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 1 2 R topics documented: BANOVAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 BANOVAmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 BANOVAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 BANOVAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 bye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 demoBANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 demomenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 demomenu1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 demopara . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 demosize . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 description_AIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 description_ARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 description_BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 description_drug . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 description_drugcode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 description_import . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 description_load . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 description_Multipledrugcode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 description_NCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 description_NCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 description_NCAinput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 description_ParaMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 description_ParaNCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 description_ParaNCAinput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 description_plot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 description_Repdrugcode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 description_RepMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 description_RepNCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 description_RepNCAinput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 description_size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 description_size_para . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 description_TOST1_lnAUC0INF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 description_TOST1_lnAUC0t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 description_TOST1_lnCmax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 description_TOST_lnAUC0INF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 description_TOST_lnAUC0t . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 description_TOST_lnCmax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 description_TTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 description_TTTAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 description_TTTARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 description_version . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 entertitle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 entertitle.demo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 go . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 logdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Multiple1menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Multipleaic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 MultipleAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 R topics documented: 3 MultipleAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 MultipleAIC_BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 MultipleARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 MultipleARS.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 MultipleARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 MultipleARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 MultipleBANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 MultipleBANOVAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 MultipleBANOVAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 MultipleBANOVAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 MultipleBANOVAmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 MultipleBANOVAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 MultipleBANOVAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Multipledata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 MultipledemoBANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Multipledemomenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Multipledemomenu1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Multiplego . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Multiplemenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 MultipleNCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 MultipleNCA.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 MultipleNCA.BANOVAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 MultipleNCA.BANOVAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 MultipleNCA.BANOVAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 MultipleNCA.BANOVAmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 MultipleNCAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 MultipleNCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 MultipleNCAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 MultipleNCAdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 MultipleNCAdemo.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 MultipleNCAmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 MultipleNCAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 MultipleNCAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 MultipleNCAsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 MultipleNCAselect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 MultipleNCAselect.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 MultipleNCAselectdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 MultipleNCAselectdemo.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 MultipleNCAselectsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 MultipleNCAselectsave.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Multiplentertitle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Multiplentertitle.demo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 MultipleParaAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 MultipleParaAIC.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 MultipleParaAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 MultipleParaAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 MultipleParaARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 MultipleParaARS.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 4 R topics documented: MultipleParaARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 MultipleParaARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 MultipleParadata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 MultipleParademomenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 MultipleParademomenu1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 MultipleParademoMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 MultipleParamenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 MultipleParaMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 MultipleParaMIXanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 MultipleParaMIXcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 MultipleParaMIXdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 MultipleParaMIXmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 MultipleParaMIXoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 MultipleParaNCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 MultipleParaNCA.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 MultipleParaNCA.MIXanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 MultipleParaNCA.MIXcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 MultipleParaNCA.MIXdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 MultipleParaNCA.MIXmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 MultipleParaNCAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 MultipleParaNCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 MultipleParaNCAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 MultipleParaNCAdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 MultipleParaNCAdemo.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 MultipleParaNCAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 MultipleParaNCAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 MultipleParaNCAsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 MultipleParaNCAselect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 MultipleParaNCAselect.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 MultipleParaNCAselectdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 MultipleParaNCAselectdemo.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 MultipleParaNCAselectsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 MultipleParaNCAselectsave.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 MultipleParaTTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 MultipleParaTTT.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 MultipleParaTTTAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 MultipleParaTTTAIC.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 MultipleParaTTTAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 MultipleParaTTTAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 MultipleParaTTTARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 MultipleParaTTTARS.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 MultipleParaTTTARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 MultipleParaTTTARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 MultipleParaTTTdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 MultipleParaTTToutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Multipleplotsingle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Multipleplotsingle.para . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Multiplestat1menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 R topics documented: 5 Multiplestatmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 MultipleTTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 MultipleTTT.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 MultipleTTTAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 MultipleTTTAIC.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 MultipleTTTAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 MultipleTTTAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 MultipleTTTARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 MultipleTTTARS.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 MultipleTTTARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 MultipleTTTARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 MultipleTTTdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 MultipleTTToutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 NCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 NCA.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 NCA.BANOVAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 NCA.BANOVAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 NCA.BANOVAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 NCA.BANOVAmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 NCAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 NCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 NCAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 NCAdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 NCAdemo.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 NCAmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 NCAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 NCAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 NCAsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 NCAselect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 NCAselect.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 NCAselectdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 NCAselectdemo.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 NCAselectsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 NCAselectsave.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 ParaAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 ParaAIC.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 ParaAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 ParaAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 ParaARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 ParaARS.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 ParaARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 ParaARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Paradata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Parademomenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Parademomenu1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 ParademoMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Paralleldata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Paramenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 6 R topics documented: ParaMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 ParaMIXanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 ParaMIXcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 ParaMIXdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 ParaMIXmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 ParaMIXoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 ParaNCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 ParaNCA.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 ParaNCA.MIXanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 ParaNCA.MIXcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 ParaNCA.MIXdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 ParaNCA.MIXmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 ParaNCAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 ParaNCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 ParaNCAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 ParaNCAdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 ParaNCAdemo.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 ParaNCAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 ParaNCAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 ParaNCAsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 ParaNCAselect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 ParaNCAselect.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 ParaNCAselectdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 ParaNCAselectdemo.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 ParaNCAselectsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 ParaNCAselectsave.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 ParaTTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 ParaTTT.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 ParaTTTAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 ParaTTTAIC.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 ParaTTTAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 ParaTTTAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 ParaTTTARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 ParaTTTARS.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 ParaTTTARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 ParaTTTARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 ParaTTTdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 ParaTTToutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 plotsingle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 plotsingle.para . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 plotsingle.Rep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 prdcount . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Repaic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 RepAIC.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 RepAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 RepAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 RepARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 RepARS.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 R topics documented: 7 RepARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 RepARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 Repdemomenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Repdemomenu1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 RepdemoMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Replicateddata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Repmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 RepMIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 RepMIXanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 RepMIXcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 RepMIXdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 RepMIXmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 RepMIXoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 RepNCA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 RepNCA.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 RepNCA.MIXanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 RepNCA.MIXcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 RepNCA.MIXdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 RepNCA.MIXmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 RepNCAanalyze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 RepNCAcsv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 RepNCAdata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 RepNCAdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 RepNCAdemo.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 RepNCAoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 RepNCAplot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 RepNCAsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 RepNCAselect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 RepNCAselect.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 RepNCAselectdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 RepNCAselectdemo.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 RepNCAselectsave . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 RepNCAselectsave.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 RepTTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 RepTTT.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 RepTTTAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 RepTTTAIC.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 RepTTTAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 RepTTTAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 RepTTTARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 RepTTTARS.MIX . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 RepTTTARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 RepTTTARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 RepTTTdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 RepTTToutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Singlego . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 sizemenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 stat1menu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 8 AICdemo statmenu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 TotalSingledata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 TTT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 TTT.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 TTTAIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 TTTAIC.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 TTTAICdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 TTTAICoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 TTTARS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 TTTARS.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 TTTARSdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 TTTARSoutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 TTTdemo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 TTTdemo.BANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 TTToutput . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 xtick . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 ytick . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 Index 103 aic Akaike information criterion (AIC) method Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). AICdemo Akaike information criterion (AIC) method for demo function Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). AICoutput 9 AICoutput Output for Adjusted R squared (ARS) method Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt AIC_BANOVA Akaike information criterion (AIC) method and ANOVA Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. ARS Adjusted R squared (ARS) method Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. 10 ARSdemo.BANOVA ARS.BANOVA Adjusted R squared (ARS) method and ANOVA Description Adjusted R squared (ARS) method: This method selects data points to estimate lambda(z) based on the maximun adjustedRsqured values. It starts with the last three data points fromthe concentration- time course, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on un- til it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. ARSdemo Adjusted R squared (ARS) method for demo function Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. ARSdemo.BANOVA Adjusted R squared (ARS) method and ANOVA for demo function Description Adjusted R squared (ARS) method: This method selects data points to estimate lambda(z) based on the maximun adjustedRsqured values. It starts with the last three data points fromthe concentration- time course, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on un- til it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. ARSoutput 11 ARSoutput Output for Adjusted R squared (ARS) method Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt From: NCAoutput BANOVA Statistical analysis (ANOVA(lm), 90CI...) Description With a two-treatment, two-period, two-sequence randomized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. We investigate the assessment of equivalence in intra-subject variabilities of bioavailability between formulations. Point and interval estimates for the inter-subject and intra-subject variabilities are also provided. Moreover, a normal distribution test procedure based on Spearmans rank and Pearsons correlation coefcient and Pitman-Morgans adjusted F test are provided. Finally, several tests for assumptions using the inter-subject and intra-subject residuals are dis- cussed. Statistical tests for detection of outlying subjects such as Hotelling T2 are presented. References 1. Chow SC and Liu JP. Design and analysis of bioavailability- bioequivalence studies. Chapman & Hall/CRC, New York (2009). 2. Liu JP and Weng CS. Detection of outlying data in bioavailability- bioequivalence studies. Statist. Med. 10, 1375-1389 (1991). 12 BANOVAmenu BANOVAanalyze ANOVA function Description Data for ANOVA References Guidance for Industry. Statistical approaches to establishing Bioequivalence. BANOVAcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. BANOVAdata Input/Edit data for ANOVA function Description ->subject no.(subj) ->drug 1:Reference 2:Test ->sequence (seq) Sequence 1:Reference>Test se- quence Sequence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Pe- riod 2: second treatmetn period ->Cmax ->AUC0t: area under the predicted plasma concentration time curve for test data. (time = 0 to t) ->AUC0INF: area under the predicted plasma concentration time curve for test data. (time = 0 to innity) ->LnCmax: Log-transformed Cmax ->LnAUC0t: Log-transformed AUC0t ->LnAUC0INF: Log-transformed AUC0INF BANOVAmenu List of ANOVA Menu Description You can use the functions as follows: 1.Statistical analysis (ANOVA(lm), 90CI...) 2.Demo for Statistical analysis (ANOVA(lm), 90CI...) BANOVAoutput 13 BANOVAoutput Output of ANOVA function Description We provides several txt outputs. 1.ANOVA stat.txt >ANOVA:Cmax, AUC0t, AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf) >90CI: ln(Cmax), ln(AUC0t), and ln(AUC0inf) BANOVAplot BANOVAplot Description We provides several pdf. outputs about BANOVA plots for outlier detections. 1.Normal Probabil- ity Plot of lnCmax (intrasubj) 2.Normal Probability Plot of lnCmax (intersubj) 3.lnCmax(expected value) vs. studentized residuals(intrasubj) 4.lnCmax(expected value) vs. studentized residuals(intersubj) 5.Normal Probability Plot of lnAUC0t (intrasubj) 6.Normal Probability Plot of lnAUC0t (inter- subj) 7.lnAUC0t(expected value) vs. studentized residuals(intrasubj) 8.lnAUC0t(expected value) vs. studentized residuals(intersubj) 9.Normal Probability Plot of lnAUC0INF (intrasubj) 10.Nor- mal Probability Plot of lnAUC0INF (intersubj) 11.lnAUC0INF(expected value) vs. studentized residuals(intrasubj) 12.lnAUC0INF(expected value) vs. studentized residuals(intersubj) bye The nal step Menu Description try again or leave bear package. demoBANOVA Statistical analysis (ANOVA(lm), 90CI...)for demo le Description With a two-treatment, two-period, two-sequence randomized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. 14 description_AIC demomenu menu for NCA demo le Description lambda z est. from the exact 3 data points, lambda z est. with adjusted R sq. (ARS), lambda z est. with Akaike information criterion (AIC), lambda z est. with Two-Times-Tmax method (TTT), lambda z est. with TTT and ARS, lambda z est. with TTT and AIC demomenu1 menu for NCA demo le Description lambda z est. from the exact 3 data points> Statistical analysis, lambda z est. with adjusted R sq. (ARS)> Statistical analysis, lambda z est. with Akaike information criterion (AIC)> Statistical analysis, lambda z est. with Two-Times-Tmax method (TTT)> Statistical analysis, lambda z est. with TTT and ARS> Statistical analysis, lambda z est. with TTT and AIC> Statistical analysis, demopara Demo for sample size estimation Description Demo le for sample size estimation (crossover and replicated study)function demosize Demo for sample size estimation Description Demo le for sample size estimation (crossover and replicated study)function description_AIC Description for Akaike information criterion (AIC) method Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). description_ARS 15 description_ARS Description for Adjusted R squared (ARS) method Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. description_BANOVA Description for ANOVA Description Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. description_drug Description for drug Description drug 1: Ref. drug 2: Test description_drugcode Description for drug code Description Data Codes: Drug: 1: Ref. 2: Test Sequence: 1: Ref. > Test 2: Test > Ref. Period: 1: 1st- treatment period 2: 2nd-treatment period 16 description_NCAcsv description_import Description for import csv Description Description for import csv le description_load Description for load Rdata Description Description for load Rdata le description_Multipledrugcode Description for drug code for multiple study Description Data Codes: Drug: 1: Ref. 2: Test Sequence: 1: Ref. > Test 2: Test > Ref. Period: 1: 1st- treatment period 2: 2nd-treatment period description_NCA Description for Noncompartmental analysis (NCA) Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. description_NCAcsv Description for NCA csv le Description Data le should consist of row1: column title, such as subj, seq, prd, time, conc & etc. column1: subject no.(subj) column2: sequence (seq) -> Sequence = 1 if Ref.>Test -> Sequence = 2 if Test >Ref. column3: period (prd) -> Period = 1: the 1st-treatment period -> Period = 2: the 2nd- treatment period column4: sampling time column5: drug plasma/serum/blood concentration (conc) description_NCAinput 17 description_NCAinput Description for NCA input data Description Input/Edit Data -> subject no.(subj) -> sequence (seq) 1:Ref.>Test 2:Test>Ref. -> period (prd) 1: 1st-treatment period 2: 2nd-treatment period -> sampling time -> drug plasma/serum/blood concentration (conc) description_ParaMIX Description for lme for parallel study Description With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. description_ParaNCAcsv Description for NCA csv le for parallel study Description Data le should consist of row1: column title, such as subj, drug, time, conc &etc. column1: subject no.(subj) column2: treatment (drug) column3: sampling time column4: drug plasma/serum/blood concentration (conc) description_ParaNCAinput Description for NCA input data for parallel study Description Input/Edit Data -> subject no.(subj) -> treatment (drug) 1: Ref. 2: Test -> sampling time -> drug plasma/serum/blood concentration (conc) 18 description_RepNCAcsv description_plot Description for plot Description Authors: Hsin-ya Lee, Yung-jin Lee 100, Shih-chuan 1st Rd. College of Pharmacy, Kaohsiung Medical University, Kaoshiung, Taiwan 80708 E-mail: hsinyalee@gmail.com, pkpd.taiwan@gmail.com bears website: http://pkpd.kmu.edu.tw/bear R website: www.r-project.org description_Repdrugcode Description of drug code for replicated study Description Data Codes: Drug: 1: Ref. 2: Test description_RepMIX Description for lme for replicated study Description With a two-treatment, more than two period, two-sequence randomized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the ad- justed differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. description_RepNCAcsv Description of NCA csv le for replicated study Description Data le should consist of row1: column title, such as subj, seq, prd, time, conc & etc. column1: subject no.(subj) column2: sequence (seq) -> Sequence = 1 if Ref.>Test -> Sequence = 2 if Test >Ref. column3: period (prd) -> Period = 1: the 1st-treatment period -> Period = 2: the 2nd- treatment period column4: treatment (drug) column5: sampling time column6: drug plasma/serum/blood concentra- tion (conc) description_RepNCAinput 19 description_RepNCAinput Description for NCA input data for replicated study Description Input/Edit Data -> subject no.(subj) -> sequence (seq) ex. 4 periods 1:Ref.>Test>Ref.>Test 2:Test>Ref.>Test>Ref. or ex. 3 periods 1:Ref.>Test>Test 2:Test>Ref.>Ref. -> period (prd) 1: 1st-treatment period 2: 2nd-treatment period 3: 3rd-treatment period 4: 4th-treatment period -> treatment (drug) 1: Ref. 2: Test -> sampling time -> drug plasma/serum/blood concentration (conc) description_size Description for sample size input for crossover and replicated study Description Required data 1. Theta is the ratio in average BA between the two formulations expressed in per- centage of the average reference BA. 2. Theta=Ut/Ur, where Ut and Ur denote the median BA for the Test and the Reference products. 3. CV stands for the intra-subject coefcient of variation. description_size_para Description for sample size input for parallel study Description Required data 1. Theta is the ratio in average BA between the two formulations expressed in per- centage of the average reference BA. 2. Theta=Ut/Ur, where Ut and Ur denote the median BA for the Test and the Reference products. 3. CV stands for the inter-subject coefcient of variation. 20 description_TOST1_lnAUC0t description_TOST1_lnAUC0INF Description for Two One-Sided Test for lnAUC0INF Description Interpretation: Ho: MEAN-test/MEAN-ref =< ln(lower acceptance) or MEAN-test/MEAN-ref >= ln(Upper acceptance) Ha: ln(lower acceptance) < MEAN-test/MEAN-ref < ln(Upper acceptance) Because all P values are less than 0.05, we will reject the null hypothesis (Ho). References 1. Chow SC and Liu JP. Design and Analysis of Bioavailability- Bioequivalence Studies. 3rd ed., Chapman & Hall/CRC, New York (2009). 2. Schuirmann DJ. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval.Biometrics, 37, 617(1981). 3. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for as- sessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceu- tics, 15, 657-680 (1987). 4. Anderson S and Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods, 12, 2663-2692 (1983). description_TOST1_lnAUC0t Description for Two One-Sided Test for lnAUC0t Description Interpretation: Ho: MEAN-test/MEAN-ref =< ln(lower acceptance) or MEAN-test/MEAN-ref >= ln(Upper acceptance) Ha: ln(lower acceptance) < MEAN-test/MEAN-ref < ln(Upper acceptance) Because all P values are less than 0.05, we will reject the null hypothesis (Ho). References 1. Chow SC and Liu JP. Design and Analysis of Bioavailability- Bioequivalence Studies. 3rd ed., Chapman & Hall/CRC, New York (2009). 2. Schuirmann DJ. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval.Biometrics, 37, 617(1981). 3. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for as- sessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceu- tics, 15, 657-680 (1987). 4. Anderson S and Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods, 12, 2663-2692 (1983). description_TOST1_lnCmax 21 description_TOST1_lnCmax Description for Two One-Sided Test for lnCmax Description Interpretation: Ho: MEAN-test/MEAN-ref =< ln(lower acceptance) or MEAN-test/MEAN-ref >= ln(Upper acceptance) Ha: ln(lower acceptance) < MEAN-test/MEAN-ref < ln(Upper acceptance) Because all P values are less than 0.05, we will reject the null hypothesis (Ho). References 1. Chow SC and Liu JP. Design and Analysis of Bioavailability- Bioequivalence Studies. 3rd ed., Chapman & Hall/CRC, New York (2009). 2. Schuirmann DJ. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval.Biometrics, 37, 617(1981). 3. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for as- sessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceu- tics, 15, 657-680 (1987). 4. Anderson S and Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods, 12, 2663-2692 (1983). description_TOST_lnAUC0INF Description for Two One-Sided Test for lnAUC0INF Description Interpretation: Ho: MEAN-test/MEAN-ref =< ln(lower acceptance) or MEAN-test/MEAN-ref >= ln(Upper acceptance) Ha: ln(lower acceptance) < MEAN-test/MEAN-ref < ln(Upper acceptance) If at least one of P value is more than 0.05, we will not reject the null hypothesis (Ho). References 1. Chow SC and Liu JP. Design and Analysis of Bioavailability- Bioequivalence Studies. 3rd ed., Chapman & Hall/CRC, New York (2009). 2. Schuirmann DJ. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval.Biometrics, 37, 617(1981). 3. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for as- sessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceu- tics, 15, 657-680 (1987). 4. Anderson S and Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods, 12, 2663-2692 (1983). 22 description_TOST_lnCmax description_TOST_lnAUC0t Description for Two One-Sided Test for lnAUC0t Description Interpretation: Ho: MEAN-test/MEAN-ref =< ln(lower acceptance) or MEAN-test/MEAN-ref >= ln(Upper acceptance) Ha: ln(lower acceptance) < MEAN-test/MEAN-ref < ln(Upper acceptance) If at least one of P value is more than 0.05, we will not reject the null hypothesis (Ho). References 1. Chow SC and Liu JP. Design and Analysis of Bioavailability- Bioequivalence Studies. 3rd ed., Chapman & Hall/CRC, New York (2009). 2. Schuirmann DJ. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval.Biometrics, 37, 617(1981). 3. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for as- sessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceu- tics, 15, 657-680 (1987). 4. Anderson S and Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods, 12, 2663-2692 (1983). description_TOST_lnCmax Description for Two One-Sided Test for lnCmax Description Interpretation: Ho: MEAN-test/MEAN-ref =< ln(lower acceptance) or MEAN-test/MEAN-ref >= ln(Upper acceptance) Ha: ln(lower acceptance) < MEAN-test/MEAN-ref < ln(Upper acceptance) If at least one of P value is more than 0.05, we will not reject the null hypothesis (Ho). References 1. Chow SC and Liu JP. Design and Analysis of Bioavailability- Bioequivalence Studies. 3rd ed., Chapman & Hall/CRC, New York (2009). 2. Schuirmann DJ. On hypothesis testing to determine if the mean of a normal distribution is continued in a known interval.Biometrics, 37, 617(1981). 3. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for as- sessing the equivalence of average bioavailability. Journal of Pharmacokinetics and Biopharmaceu- tics, 15, 657-680 (1987). 4. Anderson S and Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods, 12, 2663-2692 (1983). description_TTT 23 description_TTT Description for Two Times Tmax (TTT) method Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). description_TTTAIC Description for Two-Times-Tmax (TTT) and Akaike information crite- rion (AIC) Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). description_TTTARS Description for Two Times Tmax (TTT) and Adjusted R squared (ARS) Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). 24 go description_version Description for version Description Authors: Hsin-ya Lee, Yung-jin Lee 100, Shih-chuan 1st Rd. College of Pharmacy, Kaohsiung Medical University, Kaoshiung, Taiwan 80708 E-mail: hsinyalee@gmail.com, pkpd.taiwan@gmail.com bears website: http://pkpd.kmu.edu.tw/bear R website: www.r-project.org entertitle enter Dose, xaxis and yaxis Description enter Dose, xaxis and yaxis entertitle.demo enter Dose, xaxis and yaxis for demo le Description enter Dose, xaxis and yaxis go List of bear Menu Description You can use the functions as follows: 1.Single dose study 2.Multiple dose study logdata 25 logdata Sample size estimation for log transformation data for crossover and replicated study Description This function will help you to choose appropriate sample size. References R-code based on SAS-code by (1) B. Jones and M.G. Kenward Design and Analysis of Cross- Over Trials Chapman & Hall/CRC, Boca Raton (2nd Edition 2000) (2) S. Patterson and B. Jones Bioequivalence and Statistics in Clinical Pharmacology Chapman & Hall/CRC, Boca Raton (2006) /*** WARNING : PROGRAM OFFERED FOR USE WITHOUT ANY GUARANTEES ***/ /*** NO LIABILITY IS ACCEPTED FOR ANY LOSS RESULTING FROM USE OF ***/ /*** THIS SET OF SAS INTRUCTIONS ***/ Modication of degrees of freedom according to a personal message by D. Hauschke (E-mail 2006-01-05) Tested in R-versions 2.6.2 / 2.5.1 / 1.9.1 / 1.9.0 2008-04-04 Sample size R-code was referred from Helmut Schuetz BEBAC - Consultancy services for Bioequivalence and Bioavailability Studies 1070 Vienna, Austria Hauschke D, Steinijans VW, Diletti E and Burke M. Sample size determination for bioequivalence assessment using a multiplicative model. J. Pharmacokin. Biopharm. 20:557-561 (1992). Multiple1menu List of NCA non-replicated and replicated study Description You can use the functions as follows: 1. NCA for non-replicated crossover study, 2. NCA for replicated crossover study, Multipleaic Akaike information criterion (AIC) method for multiple study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). 26 MultipleAIC_BANOVA MultipleAICdemo Akaike information criterion (AIC) method for demo function Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). MultipleAICoutput Output for Adjusted R squared (ARS) method for multiple dose Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt MultipleAIC_BANOVA Akaike information criterion (AIC) method and ANOVA for multiple dose Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. MultipleARS 27 MultipleARS Adjusted R squared (ARS) method for multiple dose Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. MultipleARS.BANOVA Adjusted R squared (ARS) method and ANOVA for multiple dose Description Adjusted R squared (ARS) method: This method selects data points to estimate lambda(z) based on the maximun adjustedRsqured values. It starts with the last three data points fromthe concentration- time course, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on un- til it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. MultipleARSdemo Adjusted R squared (ARS) method for demo function for multiple dose Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. 28 MultipleBANOVA MultipleARSoutput Output for Adjusted R squared (ARS) method for multiple dose Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt MultipleBANOVA Statistical analysis (ANOVA(lm), 90CI...) Description With a two-treatment, two-period, two-sequence randomized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. We investigate the assessment of equivalence in intra-subject variabilities of bioavailability between formulations. Point and interval estimates for the inter-subject and intra-subject variabilities are also provided. Moreover, a normal distribution test procedure based on Spearmans rank and Pearsons correlation coefcient and Pitman-Morgans adjusted F test are provided. Finally, several tests for assumptions using the inter-subject and intra-subject residuals are dis- cussed. Statistical tests for detection of outlying subjects such as Hotelling T2 are presented. References 1. Chow SC and Liu JP. Design and analysis of bioavailability- bioequivalence studies. Chapman & Hall/CRC, New York (2009). 2. Liu JP and Weng CS. Detection of outlying data in bioavailability- bioequivalence studies. Statist. Med. 10, 1375-1389 (1991). MultipleBANOVAanalyze 29 MultipleBANOVAanalyze ANOVA function for multiple dose Description Data for ANOVA References Guidance for Industry. Statistical approaches to establishing Bioequivalence. MultipleBANOVAcsv choose separator and decimal type for multiple dose Description Separator : comma, semicolon ,white space. Decimal: comma, point. MultipleBANOVAdata Input/Edit data for ANOVA function for multiple dose Description ->subject no.(subj) ->drug 1:Reference 2:Test ->sequence (seq) Sequence 1:Reference>Test se- quence Sequence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Pe- riod 2: second treatmetn period ->Css_max ->AUCss(tau): area under the predicted plasma con- centration time curve (time = tau) ->LnCss_max: Log-transformed Cmax ->LnAUC0ss(tau): Log- transformed AUC0ss(tau) MultipleBANOVAmenu List of ANOVA Menu for multiple dose Description You can use the functions as follows: 1.Statistical analysis (ANOVA(lm), 90CI...) 2.Demo for Statistical analysis (ANOVA(lm), 90CI...) 30 MultipledemoBANOVA MultipleBANOVAoutput Output of ANOVA function for multiple dose Description We provides several txt outputs. 1.ANOVA stat.txt >ANOVA:Css_max, AUCss(tau), lnCss_max, lnAUCss(tau) >90CI: lnCss_max, lnAUCss(tau) MultipleBANOVAplot BANOVAplot for multiple dose Description We provides several pdf. outputs about BANOVA plots for outlier detections. 1.Normal Probability Plot of lnCss_max (intrasubj) 2.Normal Probability Plot of lnCss_max (intersubj) 3.lnCss_max(expected value) vs. studentized residuals(intrasubj) 4.lnCss_max(expected value) vs. studentized resid- uals(intersubj) 5.Normal Probability Plot of lnAUCss(tau) (intrasubj) 6.Normal Probability Plot of lnAUCss(tau) (intersubj) 7.lnAUCss(tau)(expected value) vs. studentized residuals(intrasubj) 8.lnAUCss(tau)(expected value) vs. studentized residuals(intersubj) Multipledata Data for NCA analyze for multiple dose Description The data give the data of subjects, drug, sequence, period, time, and concentration. MultipledemoBANOVA Statistical analysis (ANOVA(lm), 90CI...)for demo le Description With a two-treatment, two-period, two-sequence randomized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. Multipledemomenu 31 Multipledemomenu menu for NCA demo le Description lambda z est. from the exact 3 data points, lambda z est. with adjusted R sq. (ARS), lambda z est. with Akaike information criterion (AIC), lambda z est. with Two-Times-Tmax method (TTT), lambda z est. with TTT and ARS, lambda z est. with TTT and AIC Multipledemomenu1 menu for NCA demo le Description lambda z est. from the exact 3 data points> Statistical analysis, lambda z est. with adjusted R sq. (ARS)> Statistical analysis, lambda z est. with Akaike information criterion (AIC)> Statistical analysis, lambda z est. with Two-Times-Tmax method (TTT)> Statistical analysis, lambda z est. with TTT and ARS> Statistical analysis, lambda z est. with TTT and AIC> Statistical analysis, Multiplego List of bear Menu Description You can use the functions as follows: 1.Sample size estimation for average BE 2.Noncompartment Analysis (NCA) 3.ANOVA 4.NCA->ANOVA Multiplemenu List of NCA non-replicated and replicated study Description You can use the functions as follows: 1. NCA for non-replicated crossover study, 2. NCA for replicated crossover study, 32 MultipleNCA.BANOVAcsv MultipleNCA Noncompartmental analysis (NCA) for multiple dose Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. MultipleNCA.BANOVA NCA and ANOVA for multiple dose Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. MultipleNCA.BANOVAanalyze NCA and ANOVA function for multiple dose Description This function includes both NCAanalyze and BANOVAanalyze functions. MultipleNCA.BANOVAcsv choose separator and decimal type for multiple dose Description Separator : comma, semicolon ,white space. Decimal: comma, point. MultipleNCA.BANOVAdata 33 MultipleNCA.BANOVAdata Input/Edit data for NCA and ANOVA function for multiple dose Description Input/Edit Data ->subject no.(subj) ->sequence (seq) Sequence 1:Reference>Test sequence Se- quence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Period 2: second treatmetn period ->time ->concentration (conc) MultipleNCA.BANOVAmenu List of NCA and ANOVA Menu for multiple dose Description You can use the functions as follows: 1.NCA>ANOVA 2.Run demo for NCA > Statistical anal- ysis MultipleNCAanalyze NCA analyze function for multiple dose Description We provide noncompartmental analysis (NCA) approach to compute AUCs and terminal elimina- tion rate constant (kel) for plasma concentration. Here we provide six methods, exact 3 data points, ARS, TTT, AIC, TTT and ARS, and TTT and AIC. MultipleNCAcsv choose separator and decimal type for multiple dose Description Separator : comma, semicolon ,white space. Decimal: comma, point. 34 MultipleNCAmenu MultipleNCAdata Input/Edit data for NCA function for multiple dose Description Input/Edit Data ->subject no.(subj) ->sequence (seq) Sequence 1:Reference>Test sequence Se- quence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Period 2: second treatmetn period ->time ->concentration (conc) MultipleNCAdemo Select the exact 3 data points(NCA) for demo function for multiple dose Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. MultipleNCAdemo.BANOVA Select the exact 3 data points(NCA) and ANOVA for demo function for multiple dose Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. MultipleNCAmenu List of NCA 2x2x2 Menu for multiple dose Description You can use the functions as follows: 1.multiple Dose 2.Demo for multiple Dose MultipleNCAoutput 35 MultipleNCAoutput Output of NCA for multiple dose Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt MultipleNCAplot NCAplot for multiple dose Description We provides several pdf. outputs about NCA plots. 1.Conc. vs. Time for individual subjects 2.Log10(Conc.) vs. Time for individual subjects 3.Test (.Conc. vs. Time) for all subjects 4.Refer- ence (.Conc. vs. Time) for all subjects 5.Conc.(mean+-sd) vs Time for test and reference MultipleNCAsave Save NCA outputs for multiple dose Description This function can save the results after NCA. MultipleNCAselect Select the exact 3 points in NCA for multiple dose Description This function can help users select the exact 3 points for NCA function. MultipleNCAselect.BANOVA Select the exact 3 points in NCA and ANOVA for multiple dose Description This function can help users select the exact 3 points for NCA function. 36 Multiplentertitle MultipleNCAselectdemo Select the exact 3 points in NCA for demo function for multiple dose Description This function can help users select the exact 3 points for NCA function. MultipleNCAselectdemo.BANOVA Select the exact 3 points in NCA and ANOVA for demo function for multiple dose Description This function can help users select the exact 3 points for NCA function. MultipleNCAselectsave Select the exact 3 points in NCA and Save the data for multiple dose Description This function can save the exact 3 points. MultipleNCAselectsave.BANOVA Select the exact 3 points in NCA and Save the data for multiple dose Description This function can save the exact 3 points. Multiplentertitle enter Dose, tau, time of last dose, xaxis and yaxis for multiple dose Description enter Dose, tau, time of last dose, xaxis and yaxis Multiplentertitle.demo 37 Multiplentertitle.demo enter Dose, tau, time of last dose, xaxis and yaxis for multiple dose for demo le Description enter Dose, tau, time of last dose, xaxis and yaxis MultipleParaAIC Akaike information criterion (AIC) method for parallel with multiple dose study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). MultipleParaAIC.MIX Akaike information criterion (AIC) method->statictics for parallel with multiple dose study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). 38 MultipleParaARS MultipleParaAICdemo Akaike information criterion (AIC) method for demo function for par- allel with multiple dose study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). MultipleParaAICoutput Output for Adjusted R squared (ARS) method for parallel with multiple dose study Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt MultipleParaARS Adjusted R squared (ARS) method for parallel with multiple dose study Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. MultipleParaARS.MIX 39 MultipleParaARS.MIX Adjusted R squared (ARS) method and lme for parallel with multiple dose study Description Adjusted R squared (ARS) method: This method selects data points to estimate lambda(z) based on the maximun adjustedRsqured values. It starts with the last three data points fromthe concentration- time course, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on un- til it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. MultipleParaARSdemo Adjusted R squared (ARS) method for demo function for parallel with multiple dose study Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. MultipleParaARSoutput Output for Adjusted R squared (ARS) method for parallel study Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt 40 MultipleParademoMIX MultipleParadata Data for NCA analyze for parallel with multiple dose study Description The data give the data of subjects, drug, time, and concentration. MultipleParademomenu menu for NCA demo le for parallel with multiple dose study Description lambda z est. from the exact 3 data points, lambda z est. with adjusted R sq. (ARS), lambda z est. with Akaike information criterion (AIC), lambda z est. with Two-Times-Tmax method (TTT), lambda z est. with TTT and ARS, lambda z est. with TTT and AIC MultipleParademomenu1 menu for NCA->Statistical analysis demo le for parallel with multi- ple dose study Description lambda z est. from the exact 3 data points> Statistical analysis, lambda z est. with adjusted R sq. (ARS)> Statistical analysis, lambda z est. with Akaike information criterion (AIC)> Statistical analysis, lambda z est. with Two-Times-Tmax method (TTT)> Statistical analysis, lambda z est. with TTT and ARS> Statistical analysis, lambda z est. with TTT and AIC> Statistical analysis, MultipleParademoMIX Statistical analysis (lme, 90CI...)for demo le for parallel with multi- ple dose study Description Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. MultipleParamenu 41 MultipleParamenu List of NCA 2x2x1 Menu for multiple dose Description You can use the functions as follows: 1.run NCA 2.Demo for NCA MultipleParaMIX Statistical analysis (lme, 90CI...) for parallel with multiple dose study Description With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. MultipleParaMIXanalyze Split data to perform lme function for parallel with multiple dose study Description Split data for lme function References Guidance for Industry. Statistical approaches to establishing Bioequivalence. MultipleParaMIXcsv choose separator and decimal type for multiple dose Description Separator : comma, semicolon ,white space. Decimal: comma, point. 42 MultipleParaNCA MultipleParaMIXdata Input/Edit data for lme function for parallel with multiple dose study Description ->subject no.(subj) ->drug 1:Reference 2:Test ->Css_max ->AUCss(tau): area under the predicted plasma concentration time curve (time = tau) ->LnCss_max: Log-transformed Cmax ->LnAUC0ss(tau): Log-transformed AUC0ss(tau) MultipleParaMIXmenu List of lme Menu for multiple dose Description You can use the functions as follows: 1.Statistical analysis (lme, 90CI...) 2.Demo for Statistical analysis (lme, 90CI...) MultipleParaMIXoutput Output of lme function for multiple dose Description We provides several txt outputs. 1.lme stat.txt >lme: Css_max, AUCss(tau), lnCss_max, lnAUCss(tau) >90CI: lnCss_max, lnAUCss(tau) MultipleParaNCA Noncompartmental analysis (NCA) for parallel with multiple dose study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. MultipleParaNCA.MIX 43 MultipleParaNCA.MIX NCA and lme for parallel study for multiple dose Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. MultipleParaNCA.MIXanalyze NCA and lme function for multiple dose Description This function includes both NCA and lme functions. MultipleParaNCA.MIXcsv choose separator and decimal type for multiple dose Description Separator : comma, semicolon ,white space. Decimal: comma, point. MultipleParaNCA.MIXdata Input/Edit data for NCA and lme function for parallel with multiple dose study Description Input/Edit Data ->subject no.(subj) ->drug ref.: 1 test: 2 ->time ->concentration (conc) 44 MultipleParaNCAdata MultipleParaNCA.MIXmenu List of NCA and lme Menu for multiple dose Description You can use the functions as follows: 1.NCA>lme 2.Run demo for NCA > Statistical analysis MultipleParaNCAanalyze NCA analyze function for parallel with multiple dose study Description We provide noncompartmental analysis (NCA) approach to compute AUCs and terminal elimina- tion rate constant (kel) for plasma concentration. Here we provide six methods, exact 3 data points, ARS, TTT, AIC, TTT and ARS, and TTT and AIC. MultipleParaNCAcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. MultipleParaNCAdata Input/Edit data for NCA function for parallel study Description Input/Edit Data ->subject no.(subj) ->drug ->time ->concentration (conc) MultipleParaNCAdemo 45 MultipleParaNCAdemo Select the exact 3 data points(NCA) for demo function for parallel study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. MultipleParaNCAdemo.MIX Select the exact 3 data points(NCA) and lme for demo function Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. MultipleParaNCAoutput Output of NCA for parallel study Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt 46 MultipleParaNCAselectdemo MultipleParaNCAplot NCAplot for parallel study Description We provides several pdf. outputs about NCA plots. 1.Conc. vs. Time for individual subjects 2.Log10(Conc.) vs. Time for individual subjects 3.Test (.Conc. vs. Time) for all subjects 4.Refer- ence (.Conc. vs. Time) for all subjects 5.Conc.(mean+-sd) vs Time for test and reference MultipleParaNCAsave Save NCA outputs for parallel study Description This function can save the results after NCA. MultipleParaNCAselect Select the exact 3 points in NCA for parallel study Description This function can help users select the exact 3 points for NCA function. MultipleParaNCAselect.MIX Select the exact 3 points in NCA and lme for parallel study Description This function can help users select the exact 3 points for NCA function. MultipleParaNCAselectdemo Select the exact 3 points in NCA for demo function for parallel study Description This function can help users select the exact 3 points for NCA function. MultipleParaNCAselectdemo.MIX 47 MultipleParaNCAselectdemo.MIX Select the exact 3 points in NCA and lme for demo function (parallel study) Description This function can help users select the exact 3 points for NCA function. MultipleParaNCAselectsave Select the exact 3 points in NCA and Save the data for parallel study Description This function can save data of the exact 3 points. MultipleParaNCAselectsave.MIX Select the exact 3 points in NCA and Save the data Description This function can save the exact 3 points. MultipleParaTTT Two Times Tmax (TTT) method for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). 48 MultipleParaTTTAIC MultipleParaTTT.MIX TTT and lme for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTAIC TTT and AIC for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTAIC.MIX 49 MultipleParaTTTAIC.MIX TTT ,AIC and lme for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. MultipleParaTTTAICdemo TTT and AIC for demo function for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). 50 MultipleParaTTTARS MultipleParaTTTAICoutput Output for TTT and AIC for parallel study Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTARS TTT and ARS for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTARS.MIX 51 MultipleParaTTTARS.MIX TTT ,ARS and lme for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTARSdemo TTT and ARS for demo function for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). 52 MultipleParaTTToutput References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTARSoutput Output for TTT and ARS for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleParaTTTdemo Two Times Tmax (TTT) method for demo function for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). MultipleParaTTToutput Output for Two Times Tmax (TTT) method for parallel study Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt Multipleplotsingle 53 Multipleplotsingle plot individual data for crossover study Description Plot for individual person for BA (conc vs. time) and ln(BA)(lnconc vs. time) Multipleplotsingle.para plot individual data for parallel study Description Plot for individual person for BA (conc vs. time) and ln(BA)(lnconc vs. time) Multiplestat1menu List of Statistical analysis non-replicated and replicated study Description You can use the functions as follows: 1. Statistical analysis for non-replicated crossover study, 2. Statistical analysis for replicated crossover study, Multiplestatmenu List of NCA>statistics non-replicated and replicated study Description You can use the functions as follows: 1. NCA for non-replicated crossover study, 2. NCA for replicated crossover study, 54 MultipleTTT.BANOVA MultipleTTT Two Times Tmax (TTT) method Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTT.BANOVA TTT and ANOVA Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTAIC 55 MultipleTTTAIC TTT and AIC Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTAIC.BANOVA TTT ,AIC and ANOVA Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. 56 MultipleTTTAICoutput MultipleTTTAICdemo TTT and AIC for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTAICoutput Output for TTT and AIC Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTARS 57 MultipleTTTARS TTT and ARS Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTARS.BANOVA TTT ,ARS and ANOVA Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. 58 MultipleTTTARSoutput References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTARSdemo TTT and ARS for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTARSoutput Output for TTT and ARS Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). MultipleTTTdemo 59 MultipleTTTdemo Two Times Tmax (TTT) method for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). MultipleTTToutput Output for Two Times Tmax (TTT) method Description We provides several txt outputs. 1. NCA PK.txt: >Css_max, Tss_max, AUCss(tau), ln(Css_max), ln(AUCss(tau)), MRTss(tau), T1/2(z), Vd/F, lambda, Clss/F, Cav and Fluctuation > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt NCA Noncompartmental analysis (NCA) Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. 60 NCA.BANOVAdata NCA.BANOVA NCA and ANOVA Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. NCA.BANOVAanalyze NCA and ANOVA function Description This function includes both NCAanalyze and BANOVAanalyze functions. NCA.BANOVAcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. NCA.BANOVAdata Input/Edit data for NCA and ANOVA function Description Input/Edit Data ->subject no.(subj) ->sequence (seq) Sequence 1:Reference>Test sequence Se- quence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Period 2: second treatmetn period ->time ->concentration (conc) NCA.BANOVAmenu 61 NCA.BANOVAmenu List of NCA and ANOVA Menu Description You can use the functions as follows: 1.NCA>ANOVA 2.Run demo for NCA > Statistical anal- ysis NCAanalyze NCA analyze function Description We provide noncompartmental analysis (NCA) approach to compute AUCs and terminal elimina- tion rate constant (kel) for plasma concentration. Here we provide six methods, exact 3 data points, ARS, TTT, AIC, TTT and ARS, and TTT and AIC. NCAcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. NCAdata Input/Edit data for NCA function Description Input/Edit Data ->subject no.(subj) ->sequence (seq) Sequence 1:Reference>Test sequence Se- quence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Period 2: second treatmetn period ->time ->concentration (conc) NCAdemo Select the exact 3 data points(NCA) for demo function Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. 62 NCAplot NCAdemo.BANOVA Select the exact 3 data points(NCA) and ANOVA for demo function Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. NCAmenu List of NCA 2x2x2 Menu Description You can use the functions as follows: 1.Single Dose 2.Demo for Single Dose NCAoutput Output of NCA Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt NCAplot NCAplot Description We provides several pdf. outputs about NCA plots. 1.Conc. vs. Time for individual subjects 2.Log10(Conc.) vs. Time for individual subjects 3.Test (.Conc. vs. Time) for all subjects 4.Refer- ence (.Conc. vs. Time) for all subjects 5.Conc.(mean+-sd) vs Time for test and reference NCAsave 63 NCAsave Save NCA outputs Description This function can save the results after NCA. NCAselect Select the exact 3 points in NCA Description This function can help users select the exact 3 points for NCA function. NCAselect.BANOVA Select the exact 3 points in NCA and ANOVA Description This function can help users select the exact 3 points for NCA function. NCAselectdemo Select the exact 3 points in NCA for demo function Description This function can help users select the exact 3 points for NCA function. NCAselectdemo.BANOVA Select the exact 3 points in NCA and ANOVA for demo function Description This function can help users select the exact 3 points for NCA function. 64 ParaAIC.MIX NCAselectsave Select the exact 3 points in NCA and Save the data Description This function can save the exact 3 points. NCAselectsave.BANOVA Select the exact 3 points in NCA and Save the data Description This function can save the exact 3 points. ParaAIC Akaike information criterion (AIC) method for parallel study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). ParaAIC.MIX Akaike information criterion (AIC) method->statictics for parallel study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). ParaAICdemo 65 ParaAICdemo Akaike information criterion (AIC) method for demo function for par- allel study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). ParaAICoutput Output for Adjusted R squared (ARS) method for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt ParaARS Adjusted R squared (ARS) method for parallel study Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. 66 ParaARSoutput ParaARS.MIX Adjusted R squared (ARS) method and lme for parallel study Description Adjusted R squared (ARS) method: This method selects data points to estimate lambda(z) based on the maximun adjustedRsqured values. It starts with the last three data points fromthe concentration- time course, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on un- til it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. ParaARSdemo Adjusted R squared (ARS) method for demo function for parallel study Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. ParaARSoutput Output for Adjusted R squared (ARS) method for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt Paradata 67 Paradata Sample size estimation for log transformation data for parallel study Description This function will help you to choose appropriate sample size. References 1. Hauschke D, Steinijans VW, Diletti E and Burke M. Sample size determination for bioequiva- lence assessment using a multiplicative model. J. Pharmacokin. Biopharm. 20:557-561 (1992). 2. Julious SA. Tutorial in biostatistics: Sample sizes for clinical trials with normal data. Statist. Med. 23:1921-1986 (2004) Parademomenu menu for NCA demo le for parallel study Description lambda z est. from the exact 3 data points, lambda z est. with adjusted R sq. (ARS), lambda z est. with Akaike information criterion (AIC), lambda z est. with Two-Times-Tmax method (TTT), lambda z est. with TTT and ARS, lambda z est. with TTT and AIC Parademomenu1 menu for NCA->Statistical analysis demo le for parallel study Description lambda z est. from the exact 3 data points> Statistical analysis, lambda z est. with adjusted R sq. (ARS)> Statistical analysis, lambda z est. with Akaike information criterion (AIC)> Statistical analysis, lambda z est. with Two-Times-Tmax method (TTT)> Statistical analysis, lambda z est. with TTT and ARS> Statistical analysis, lambda z est. with TTT and AIC> Statistical analysis, ParademoMIX Statistical analysis (lme, 90CI...)for demo le for parallel study Description Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. 68 ParaMIXanalyze Paralleldata Data for NCA analyze for parallel study Description The data give the data of subjects, drug, time, and concentration. Paramenu List of NCA 2x2x1 Menu Description You can use the functions as follows: 1.run NCA 2.Demo for NCA ParaMIX Statistical analysis (lme, 90CI...) for parallel study Description With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. ParaMIXanalyze Split data to perform lme function for parallel study Description Split data for lme function References Guidance for Industry. Statistical approaches to establishing Bioequivalence. ParaMIXcsv 69 ParaMIXcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. ParaMIXdata Input/Edit data for lme function for parallel study Description ->subject no.(subj) ->drug 1:Reference 2:Test ->Cmax ->AUC0t: area under the predicted plasma concentration time curve for test data. (time = 0 to t) ->AUC0INF: area under the predicted plasma concentration time curve for test data. (time = 0 to innity) ->LnCmax: Log-transformed Cmax ->LnAUC0t: Log-transformed AUC0t ->LnAUC0INF: Log-transformed AUC0INF ParaMIXmenu List of lme Menu Description You can use the functions as follows: 1.Statistical analysis (lme, 90CI...) 2.Demo for Statistical analysis (lme, 90CI...) ParaMIXoutput Output of lme function Description We provides several txt outputs. 1.lme stat.txt >lme:Cmax, AUC0t, AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf) >90CI: ln(Cmax), ln(AUC0t), and ln(AUC0inf) ParaNCA Noncompartmental analysis (NCA) for parallel study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. 70 ParaNCA.MIXdata ParaNCA.MIX NCA and lme for parallel study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. ParaNCA.MIXanalyze NCA and lme function Description This function includes both NCA and lme functions. ParaNCA.MIXcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. ParaNCA.MIXdata Input/Edit data for NCA and lme function for parallel study Description Input/Edit Data ->subject no.(subj) ->drug ref.: 1 test: 2 ->time ->concentration (conc) ParaNCA.MIXmenu 71 ParaNCA.MIXmenu List of NCA and lme Menu Description You can use the functions as follows: 1.NCA>lme 2.Run demo for NCA > Statistical analysis ParaNCAanalyze NCA analyze function for parallel study Description We provide noncompartmental analysis (NCA) approach to compute AUCs and terminal elimina- tion rate constant (kel) for plasma concentration. Here we provide six methods, exact 3 data points, ARS, TTT, AIC, TTT and ARS, and TTT and AIC. ParaNCAcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. ParaNCAdata Input/Edit data for NCA function for parallel study Description Input/Edit Data ->subject no.(subj) ->drug ->time ->concentration (conc) ParaNCAdemo Select the exact 3 data points(NCA) for demo function for parallel study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. 72 ParaNCAsave ParaNCAdemo.MIX Select the exact 3 data points(NCA) and lme for demo function Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. ParaNCAoutput Output of NCA for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt ParaNCAplot NCAplot for parallel study Description We provides several pdf. outputs about NCA plots. 1.Conc. vs. Time for individual subjects 2.Log10(Conc.) vs. Time for individual subjects 3.Test (.Conc. vs. Time) for all subjects 4.Refer- ence (.Conc. vs. Time) for all subjects 5.Conc.(mean+-sd) vs Time for test and reference ParaNCAsave Save NCA outputs for parallel study Description This function can save the results after NCA. ParaNCAselect 73 ParaNCAselect Select the exact 3 points in NCA for parallel study Description This function can help users select the exact 3 points for NCA function. ParaNCAselect.MIX Select the exact 3 points in NCA and lme for parallel study Description This function can help users select the exact 3 points for NCA function. ParaNCAselectdemo Select the exact 3 points in NCA for demo function for parallel study Description This function can help users select the exact 3 points for NCA function. ParaNCAselectdemo.MIX Select the exact 3 points in NCA and lme for demo function (parallel study) Description This function can help users select the exact 3 points for NCA function. ParaNCAselectsave Select the exact 3 points in NCA and Save the data for parallel study Description This function can save data of the exact 3 points. 74 ParaTTT.MIX ParaNCAselectsave.MIX Select the exact 3 points in NCA and Save the data Description This function can save the exact 3 points. ParaTTT Two Times Tmax (TTT) method for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTT.MIX TTT and lme for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. ParaTTTAIC 75 References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTAIC TTT and AIC for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTAIC.MIX TTT ,AIC and lme for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding 76 ParaTTTAICoutput only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. ParaTTTAICdemo TTT and AIC for demo function for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTAICoutput Output for TTT and AIC for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTARS 77 ParaTTTARS TTT and ARS for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTARS.MIX TTT ,ARS and lme for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (lme, 90CI...): With a two-treatment, two-sequence, one-period, parallel design, bear deploys the linear mixed effect model (lme). The statistical model includes a factor regarding only one source of variation - treatment. There are no sources of variation associated with sequence or period because there are no sequences or periods in a parallel design. Moreover, lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error. Log-transformed BA measures will also be analyzed. 78 ParaTTTARSoutput References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTARSdemo TTT and ARS for demo function for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTARSoutput Output for TTT and ARS for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). ParaTTTdemo 79 ParaTTTdemo Two Times Tmax (TTT) method for demo function for parallel study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). ParaTTToutput Output for Two Times Tmax (TTT) method for parallel study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda, and Cl/F > PKparameter sum- mary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt plotsingle plot individual data for crossover study Description Plot for individual person for BA (conc vs. time) and ln(BA)(lnconc vs. time) plotsingle.para plot individual data for parallel study Description Plot for individual person for BA (conc vs. time) and ln(BA)(lnconc vs. time) 80 RepAIC.MIX plotsingle.Rep plot individual data for replicated study Description Plot for individual person for BA (conc vs. time) and ln(BA)(lnconc vs. time) prdcount legends for plots Description The legend description for replicated study Repaic Akaike information criterion (AIC) method for replicated study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). RepAIC.MIX Akaike information criterion (AIC) method->statictics for replicated study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). RepAICdemo 81 RepAICdemo Akaike information criterion (AIC) method for demo function for repli- cated study Description This method selects data points to estimate lambda(z) based on the minimun AIC values. It starts with the last three data points from the concentration -time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). RepAICoutput Output for Adjusted R squared (ARS) method for replicated study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt RepARS Adjusted R squared (ARS) method for replicated study Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. 82 RepARSoutput RepARS.MIX Adjusted R squared (ARS) method and lme for replicated study Description Adjusted R squared (ARS) method: This method selects data points to estimate lambda(z) based on the maximun adjustedRsqured values. It starts with the last three data points fromthe concentration- time course, performing log-linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on un- til it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. Statistical analysis (lme, 90CI...): With a two-treatment, more than two period, two-sequence ran- domized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. RepARSdemo Adjusted R squared (ARS) method for demo function for replicated study Description This method selects data points to estimate lambda(z) based on the maximun adjustedR squred values. It starts with the last three data points from the concentration-time course, performing log- linear regression to calculate the slope of that tail portion of the concentration-time curve. And then the last 4 data points, the last 5 data points, on and on until it excludes the data points of Cmax. Thus, this method may exclude the data point of (Tmax, Cmax). WNL v6. has the similar algoirthms like this. RepARSoutput Output for Adjusted R squared (ARS) method for replicated study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt Repdemomenu 83 Repdemomenu menu for NCA demo le for replicated study Description lambda z est. from the exact 3 data points, lambda z est. with adjusted R sq. (ARS), lambda z est. with Akaike information criterion (AIC), lambda z est. with Two-Times-Tmax method (TTT), lambda z est. with TTT and ARS, lambda z est. with TTT and AIC Repdemomenu1 menu for NCA->Statistical analysis demo le for replicated study Description lambda z est. from the exact 3 data points> Statistical analysis, lambda z est. with adjusted R sq. (ARS)> Statistical analysis, lambda z est. with Akaike information criterion (AIC)> Statistical analysis, lambda z est. with Two-Times-Tmax method (TTT)> Statistical analysis, lambda z est. with TTT and ARS> Statistical analysis, lambda z est. with TTT and AIC> Statistical analysis, RepdemoMIX Statistical analysis (lme, 90CI...)for demo le for replicated study Description Statistical analysis (lme, 90CI...): With a two-treatment, more than two period, two-sequence ran- domized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. Replicateddata Data for NCA analyze for replicated study Description The data give the data of subjects, drug, sequence, period, time, and concentration. 84 RepMIXcsv Repmenu List of NCA 2x2xn Menu Description You can use the functions as follows: 1.run NCA 2.Demo for NCAe RepMIX Statistical analysis (lme, 90CI...) for replicated study Description With a two-treatment, more than two period, two-sequence randomized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the ad- justed differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. RepMIXanalyze Split data to perform lme function for replicated study Description Split data for lme function References Guidance for Industry. Statistical approaches to establishing Bioequivalence. RepMIXcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. RepMIXdata 85 RepMIXdata Input/Edit data for lme function for replicated study Description ->subject no.(subj) ->drug 1:Reference 2:Test ->sequence (seq) Sequence 1:Reference>Test se- quence Sequence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Pe- riod 2: second treatmetn period ->Cmax ->AUC0t: area under the predicted plasma concentration time curve for test data. (time = 0 to t) ->AUC0INF: area under the predicted plasma concentration time curve for test data. (time = 0 to innity) ->LnCmax: Log-transformed Cmax ->LnAUC0t: Log-transformed AUC0t ->LnAUC0INF: Log-transformed AUC0INF RepMIXmenu List of lme Menu Description You can use the functions as follows: 1.Statistical analysis (lme, 90CI...) 2.Demo for Statistical analysis (lme, 90CI...) RepMIXoutput Output of lme function Description We provides several txt outputs. 1.lme stat.txt >lme:Cmax, AUC0t, AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf) >90CI: ln(Cmax), ln(AUC0t), and ln(AUC0inf) RepNCA Noncompartmental analysis (NCA) for replicated study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. 86 RepNCA.MIXdata RepNCA.MIX NCA and lme for replicated study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (lme, 90CI...): With a two-treatment, more than two period, two-sequence ran- domized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. RepNCA.MIXanalyze NCA and lme function Description This function includes both NCA and lme functions. RepNCA.MIXcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. RepNCA.MIXdata Input/Edit data for NCA and lme function for replicated study Description Input/Edit Data ->subject no.(subj) ->sequence (seq) ->period (prd) Period 1: rst treatmetn period Period 2: second treatmetn period ->drug ->time ->concentration (conc) RepNCA.MIXmenu 87 RepNCA.MIXmenu List of NCA and lme Menu Description You can use the functions as follows: 1.NCA>lme 2.Run demo for NCA > Statistical analysis RepNCAanalyze NCA analyze function for replicated study Description We provide noncompartmental analysis (NCA) approach to compute AUCs and terminal elimina- tion rate constant (kel) for plasma concentration. Here we provide six methods, exact 3 data points, ARS, TTT, AIC, TTT and ARS, and TTT and AIC. RepNCAcsv choose separator and decimal type Description Separator : comma, semicolon ,white space. Decimal: comma, point. RepNCAdata Input/Edit data for NCA function for replicated study Description Input/Edit Data ->subject no.(subj) ->sequence (seq) Sequence 1:Reference>Test sequence Se- quence 2:Test>Reference sequence ->period (prd) Period 1: rst treatmetn period Period 2: second treatmetn period ->drug ->time ->concentration (conc) RepNCAdemo Select the exact 3 data points(NCA) for demo function for replicated study Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. 88 RepNCAsave RepNCAdemo.MIX Select the exact 3 data points(NCA) and lme for demo function Description Noncompartmental analysis (NCA) approach is used to compute AUCs and the terminal elimination rate constants (lambda z) for drug plasma concentration. The linear trapezoidal method is applied to calculate AUC(time 0 to the last measurable Cp). The extrapolated AUC (from time of the last measurable Cp to time innity) is equal to the last measurable Cp divided by lambda z. Statistical analysis (lme, 90CI...): With a two-treatment, more than two period, two-sequence ran- domized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. RepNCAoutput Output of NCA for replicated study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt RepNCAplot NCAplot for replicated study Description We provides several pdf. outputs about NCA plots. 1.Conc. vs. Time for individual subjects 2.Log10(Conc.) vs. Time for individual subjects 3.Test (.Conc. vs. Time) for all subjects 4.Refer- ence (.Conc. vs. Time) for all subjects 5.Conc.(mean+-sd) vs Time for test and reference RepNCAsave Save NCA outputs for replicated study Description This function can save the results after NCA. RepNCAselect 89 RepNCAselect Select the exact 3 points in NCA for replicated study Description This function can help users select the exact 3 points for NCA function. RepNCAselect.MIX Select the exact 3 points in NCA and lme for replicated study Description This function can help users select the exact 3 points for NCA function. RepNCAselectdemo Select the exact 3 points in NCA for demo function for replicated study Description This function can help users select the exact 3 points for NCA function. RepNCAselectdemo.MIX Select the exact 3 points in NCA and lme for demo function (replicated study) Description This function can help users select the exact 3 points for NCA function. RepNCAselectsave Select the exact 3 points in NCA and Save the data for replicated study Description This function can save data of the exact 3 points. 90 RepTTT.MIX RepNCAselectsave.MIX Select the exact 3 points in NCA and Save the data Description This function can save the exact 3 points. RepTTT Two Times Tmax (TTT) method for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTT.MIX TTT and lme for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). With a two-treatment, more than two period, two-sequence randomized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the ad- justed differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTAIC 91 RepTTTAIC TTT and AIC for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTAIC.MIX TTT ,AIC and lme for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). With a two-treatment, more than two period, two-sequence randomized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the ad- justed differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. 92 RepTTTAICoutput RepTTTAICdemo TTT and AIC for demo function for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTAICoutput Output for TTT and AIC for replicated study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTARS 93 RepTTTARS TTT and ARS for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTARS.MIX TTT ,ARS and lme for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). With a two-treatment, more than two period, two-sequence randomized crossover design, linear mixed-effects model may be used. The lme in nlme package is used to obtain estimates for the ad- justed differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. 94 RepTTTARSoutput References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTARSdemo TTT and ARS for demo function for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTARSoutput Output for TTT and ARS for replicated study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). RepTTTdemo 95 RepTTTdemo Two Times Tmax (TTT) method for demo function for replicated study Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). RepTTToutput Output for Two Times Tmax (TTT) method for replicated study Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda, and Cl/F > PKparameter sum- mary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt Singlego List of bear Menu Description You can use the functions as follows: 1.Sample size estimation for average BE 2.Noncompartment Analysis (NCA) 3.ANOVA 4.NCA->ANOVA sizemenu List of Sample size estimation Menu Description You can use the functions as follows: 1.Sample size estimation (Raw data) 2.Sample size estimation (Log transformation) 3.Demo for sample size estimation (Raw data) 96 TTT stat1menu List of Statistical analysis non-replicated and replicated study Description You can use the functions as follows: 1. Statistical analysis for non-replicated crossover study, 2. Statistical analysis for replicated crossover study, statmenu List of Statistical analysis non-replicated and replicated study Description You can use the functions as follows: 1. Statistical analysis for non-replicated crossover study, 2. Statistical analysis for replicated crossover study, TotalSingledata Data for NCA analyze Description The data give the data of subjects, drug, sequence, period, time, and concentration. TTT Two Times Tmax (TTT) method Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTT.BANOVA 97 TTT.BANOVA TTT and ANOVA Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTTAIC TTT and AIC Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). 98 TTTAICdemo TTTAIC.BANOVA TTT ,AIC and ANOVA Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. TTTAICdemo TTT and AIC for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply minimun AIC values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTTAICoutput 99 TTTAICoutput Output for TTT and AIC Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTTARS TTT and ARS Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). 100 TTTARSdemo TTTARS.BANOVA TTT ,ARS and ANOVA Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTTARSdemo TTT and ARS for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Then, within that range, we apply maximun ARS values to get best t. It starts with the last three data points from the concentration-time prole, performing log-linear regression to calculate the slope of that tail portion of the concentration- time curve. And then the last 4 data points, the last 5 data points, on and on until it reaches the data point right after Cmax. Thus, this method will not include the data point of (Tmax, Cmax). TTTARSoutput 101 References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTTARSoutput Output for TTT and ARS Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda z, and Cl/F > PK parameter summary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt References Scheerans C, Derendorf H and C Kloft. Proposal for a Standardised Identication of the Mono- Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos 29, 145-157 (2008). TTTdemo Two Times Tmax (TTT) method for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). 102 ytick TTTdemo.BANOVA Two Times Tmax (TTT) method and ANOVA for demo function Description The TTT method is based on the Bateman function. The Bateman function has two outstanding points. First, the maximum of the curve (Cmax at Tmax) and secondly, the inection point of the curve (Cinpt at Tinpt). The inection point of the curve describes the point where the algebraic sign of the curvature changes. Tinpt is equal to two times Tmax. Thus, The twofold of the observed Tmax value can be used as a threshold of time points to be included in the calculation of lambda(z). Statistical analysis (ANOVA(lm), 90CI...): With a two-treatment, two-period, two-sequence ran- domized crossover design, ANOVA statistical model includes factors of the following sources: sequence, subjects nested in sequences, period and treatment. ANOVA will be applied to obtain estimates for the adjusted differences between treatment means and the standard error associated with these differences. Log-transformed BA measures will also be analyzed. TTToutput Output for Two Times Tmax (TTT) method Description We provides several txt outputs. 1. NCAPK.txt: > Cmax, Tmax, AUC0t, AUC0inf, AUC0t/AUC0inf, ln(Cmax), ln(AUC0t), ln(AUC0inf), MRT0inf, T1/2, Vd/F, lambda, and Cl/F > PKparameter sum- mary (NCA outputs) 2. plots.pdf: individual linear and semilog plots, spaghetti plots, and mean conc. plots. 3. Statistical summaries.txt xtick x-tick Description Tick for plots. ytick y-tick Description Tick for plots. Index Topic misc aic, 1 AIC_BANOVA, 2 AICdemo, 2 AICoutput, 2 ARS, 3 ARS.BANOVA, 3 ARSdemo, 3 ARSdemo.BANOVA, 4 ARSoutput, 4 BANOVA, 4 BANOVAanalyze, 5 BANOVAcsv, 5 BANOVAdata, 5 BANOVAmenu, 6 BANOVAoutput, 6 BANOVAplot, 6 bye, 6 demoBANOVA, 7 demomenu, 7 demomenu1, 7 demopara, 7 demosize, 8 description_AIC, 8 description_ARS, 8 description_BANOVA, 8 description_drug, 9 description_drugcode, 9 description_import, 9 description_load, 9 description_Multipledrugcode, 9 description_NCA, 10 description_NCAcsv, 10 description_NCAinput, 10 description_ParaMIX, 10 description_ParaNCAcsv, 11 description_ParaNCAinput, 11 description_plot, 11 description_Repdrugcode, 11 description_RepMIX, 12 description_RepNCAcsv, 12 description_RepNCAinput, 12 description_size, 12 description_size_para, 13 description_TOST1_lnAUC0INF, 13 description_TOST1_lnAUC0t, 13 description_TOST1_lnCmax, 14 description_TOST_lnAUC0INF, 14 description_TOST_lnAUC0t, 15 description_TOST_lnCmax, 15 description_TTT, 16 description_TTTAIC, 16 description_TTTARS, 17 description_version, 17 entertitle, 17 entertitle.demo, 17 go, 18 logdata, 18 Multiple1menu, 18 Multipleaic, 19 MultipleAIC_BANOVA, 20 MultipleAICdemo, 19 MultipleAICoutput, 19 MultipleARS, 20 MultipleARS.BANOVA, 20 MultipleARSdemo, 21 MultipleARSoutput, 21 MultipleBANOVA, 21 MultipleBANOVAanalyze, 22 MultipleBANOVAcsv, 22 MultipleBANOVAdata, 22 MultipleBANOVAmenu, 22 MultipleBANOVAoutput, 23 MultipleBANOVAplot, 23 Multipledata, 23 103 104 INDEX MultipledemoBANOVA, 23 Multipledemomenu, 24 Multipledemomenu1, 24 Multiplego, 24 Multiplemenu, 24 MultipleNCA, 25 MultipleNCA.BANOVA, 25 MultipleNCA.BANOVAanalyze, 25 MultipleNCA.BANOVAcsv, 25 MultipleNCA.BANOVAdata, 26 MultipleNCA.BANOVAmenu, 26 MultipleNCAanalyze, 26 MultipleNCAcsv, 26 MultipleNCAdata, 27 MultipleNCAdemo, 27 MultipleNCAdemo.BANOVA, 27 MultipleNCAmenu, 27 MultipleNCAoutput, 28 MultipleNCAplot, 28 MultipleNCAsave, 28 MultipleNCAselect, 28 MultipleNCAselect.BANOVA, 28 MultipleNCAselectdemo, 29 MultipleNCAselectdemo.BANOVA, 29 MultipleNCAselectsave, 29 MultipleNCAselectsave.BANOVA, 29 Multiplentertitle, 29 Multiplentertitle.demo, 30 MultipleParaAIC, 30 MultipleParaAIC.MIX, 30 MultipleParaAICdemo, 31 MultipleParaAICoutput, 31 MultipleParaARS, 31 MultipleParaARS.MIX, 32 MultipleParaARSdemo, 32 MultipleParaARSoutput, 32 MultipleParadata, 33 MultipleParademomenu, 33 MultipleParademomenu1, 33 MultipleParademoMIX, 33 MultipleParamenu, 34 MultipleParaMIX, 34 MultipleParaMIXanalyze, 34 MultipleParaMIXcsv, 34 MultipleParaMIXdata, 35 MultipleParaMIXmenu, 35 MultipleParaMIXoutput, 35 MultipleParaNCA, 35 MultipleParaNCA.MIX, 36 MultipleParaNCA.MIXanalyze, 36 MultipleParaNCA.MIXcsv, 36 MultipleParaNCA.MIXdata, 36 MultipleParaNCA.MIXmenu, 37 MultipleParaNCAanalyze, 37 MultipleParaNCAcsv, 37 MultipleParaNCAdata, 37 MultipleParaNCAdemo, 38 MultipleParaNCAdemo.MIX, 38 MultipleParaNCAoutput, 38 MultipleParaNCAplot, 39 MultipleParaNCAsave, 39 MultipleParaNCAselect, 39 MultipleParaNCAselect.MIX, 39 MultipleParaNCAselectdemo, 39 MultipleParaNCAselectdemo.MIX, 40 MultipleParaNCAselectsave, 40 MultipleParaNCAselectsave.MIX, 40 MultipleParaTTT, 40 MultipleParaTTT.MIX, 41 MultipleParaTTTAIC, 41 MultipleParaTTTAIC.MIX, 42 MultipleParaTTTAICdemo, 42 MultipleParaTTTAICoutput, 43 MultipleParaTTTARS, 43 MultipleParaTTTARS.MIX, 44 MultipleParaTTTARSdemo, 44 MultipleParaTTTARSoutput, 45 MultipleParaTTTdemo, 45 MultipleParaTTToutput, 45 Multipleplotsingle, 46 Multipleplotsingle.para, 46 Multiplestat1menu, 46 Multiplestatmenu, 46 MultipleTTT, 47 MultipleTTT.BANOVA, 47 MultipleTTTAIC, 48 MultipleTTTAIC.BANOVA, 48 MultipleTTTAICdemo, 49 MultipleTTTAICoutput, 49 MultipleTTTARS, 50 MultipleTTTARS.BANOVA, 50 INDEX 105 MultipleTTTARSdemo, 51 MultipleTTTARSoutput, 51 MultipleTTTdemo, 52 MultipleTTToutput, 52 NCA, 52 NCA.BANOVA, 53 NCA.BANOVAanalyze, 53 NCA.BANOVAcsv, 53 NCA.BANOVAdata, 53 NCA.BANOVAmenu, 54 NCAanalyze, 54 NCAcsv, 54 NCAdata, 54 NCAdemo, 54 NCAdemo.BANOVA, 55 NCAmenu, 55 NCAoutput, 55 NCAplot, 55 NCAsave, 56 NCAselect, 56 NCAselect.BANOVA, 56 NCAselectdemo, 56 NCAselectdemo.BANOVA, 56 NCAselectsave, 57 NCAselectsave.BANOVA, 57 ParaAIC, 57 ParaAIC.MIX, 57 ParaAICdemo, 58 ParaAICoutput, 58 ParaARS, 58 ParaARS.MIX, 59 ParaARSdemo, 59 ParaARSoutput, 59 Paradata, 60 Parademomenu, 60 Parademomenu1, 60 ParademoMIX, 60 Paralleldata, 61 Paramenu, 61 ParaMIX, 61 ParaMIXanalyze, 61 ParaMIXcsv, 62 ParaMIXdata, 62 ParaMIXmenu, 62 ParaMIXoutput, 62 ParaNCA, 62 ParaNCA.MIX, 63 ParaNCA.MIXanalyze, 63 ParaNCA.MIXcsv, 63 ParaNCA.MIXdata, 63 ParaNCA.MIXmenu, 64 ParaNCAanalyze, 64 ParaNCAcsv, 64 ParaNCAdata, 64 ParaNCAdemo, 64 ParaNCAdemo.MIX, 65 ParaNCAoutput, 65 ParaNCAplot, 65 ParaNCAsave, 65 ParaNCAselect, 66 ParaNCAselect.MIX, 66 ParaNCAselectdemo, 66 ParaNCAselectdemo.MIX, 66 ParaNCAselectsave, 66 ParaNCAselectsave.MIX, 67 ParaTTT, 67 ParaTTT.MIX, 67 ParaTTTAIC, 68 ParaTTTAIC.MIX, 68 ParaTTTAICdemo, 69 ParaTTTAICoutput, 69 ParaTTTARS, 70 ParaTTTARS.MIX, 70 ParaTTTARSdemo, 71 ParaTTTARSoutput, 71 ParaTTTdemo, 72 ParaTTToutput, 72 plotsingle, 72 plotsingle.para, 72 plotsingle.Rep, 73 prdcount, 73 Repaic, 73 RepAIC.MIX, 73 RepAICdemo, 74 RepAICoutput, 74 RepARS, 74 RepARS.MIX, 75 RepARSdemo, 75 RepARSoutput, 75 Repdemomenu, 76 Repdemomenu1, 76 RepdemoMIX, 76 Replicateddata, 76 Repmenu, 77 RepMIX, 77 RepMIXanalyze, 77 106 INDEX RepMIXcsv, 77 RepMIXdata, 78 RepMIXmenu, 78 RepMIXoutput, 78 RepNCA, 78 RepNCA.MIX, 79 RepNCA.MIXanalyze, 79 RepNCA.MIXcsv, 79 RepNCA.MIXdata, 79 RepNCA.MIXmenu, 80 RepNCAanalyze, 80 RepNCAcsv, 80 RepNCAdata, 80 RepNCAdemo, 80 RepNCAdemo.MIX, 81 RepNCAoutput, 81 RepNCAplot, 81 RepNCAsave, 81 RepNCAselect, 82 RepNCAselect.MIX, 82 RepNCAselectdemo, 82 RepNCAselectdemo.MIX, 82 RepNCAselectsave, 82 RepNCAselectsave.MIX, 83 RepTTT, 83 RepTTT.MIX, 83 RepTTTAIC, 84 RepTTTAIC.MIX, 84 RepTTTAICdemo, 85 RepTTTAICoutput, 85 RepTTTARS, 86 RepTTTARS.MIX, 86 RepTTTARSdemo, 87 RepTTTARSoutput, 87 RepTTTdemo, 88 RepTTToutput, 88 Singlego, 88 sizemenu, 88 stat1menu, 89 statmenu, 89 TotalSingledata, 89 TTT, 89 TTT.BANOVA, 90 TTTAIC, 90 TTTAIC.BANOVA, 91 TTTAICdemo, 91 TTTAICoutput, 92 TTTARS, 92 TTTARS.BANOVA, 93 TTTARSdemo, 93 TTTARSoutput, 94 TTTdemo, 94 TTTdemo.BANOVA, 95 TTToutput, 95 xtick, 95 ytick, 95 aic, 1 AIC_BANOVA, 2 AICdemo, 2 AICoutput, 2 ARS, 3 ARS.BANOVA, 3 ARSdemo, 3 ARSdemo.BANOVA, 4 ARSoutput, 4 BANOVA, 4 BANOVAanalyze, 5 BANOVAcsv, 5 BANOVAdata, 5 BANOVAmenu, 6 BANOVAoutput, 6 BANOVAplot, 6 bye, 6 demoBANOVA, 7 demomenu, 7 demomenu1, 7 demopara, 7 demosize, 8 description_AIC, 8 description_ARS, 8 description_BANOVA, 8 description_drug, 9 description_drugcode, 9 description_import, 9 description_load, 9 description_Multipledrugcode, 9 description_NCA, 10 description_NCAcsv, 10 description_NCAinput, 10 description_ParaMIX, 10 description_ParaNCAcsv, 11 description_ParaNCAinput, 11 description_plot, 11 description_Repdrugcode, 11 INDEX 107 description_RepMIX, 12 description_RepNCAcsv, 12 description_RepNCAinput, 12 description_size, 12 description_size_para, 13 description_TOST1_lnAUC0INF, 13 description_TOST1_lnAUC0t, 13 description_TOST1_lnCmax, 14 description_TOST_lnAUC0INF, 14 description_TOST_lnAUC0t, 15 description_TOST_lnCmax, 15 description_TTT, 16 description_TTTAIC, 16 description_TTTARS, 17 description_version, 17 entertitle, 17 entertitle.demo, 17 go, 18 logdata, 18 Multiple1menu, 18 Multipleaic, 19 MultipleAIC_BANOVA, 20 MultipleAICdemo, 19 MultipleAICoutput, 19 MultipleARS, 20 MultipleARS.BANOVA, 20 MultipleARSdemo, 21 MultipleARSoutput, 21 MultipleBANOVA, 21 MultipleBANOVAanalyze, 22 MultipleBANOVAcsv, 22 MultipleBANOVAdata, 22 MultipleBANOVAmenu, 22 MultipleBANOVAoutput, 23 MultipleBANOVAplot, 23 Multipledata, 23 MultipledemoBANOVA, 23 Multipledemomenu, 24 Multipledemomenu1, 24 Multiplego, 24 Multiplemenu, 24 MultipleNCA, 25 MultipleNCA.BANOVA, 25 MultipleNCA.BANOVAanalyze, 25 MultipleNCA.BANOVAcsv, 25 MultipleNCA.BANOVAdata, 26 MultipleNCA.BANOVAmenu, 26 MultipleNCAanalyze, 26 MultipleNCAcsv, 26 MultipleNCAdata, 27 MultipleNCAdemo, 27 MultipleNCAdemo.BANOVA, 27 MultipleNCAmenu, 27 MultipleNCAoutput, 28 MultipleNCAplot, 28 MultipleNCAsave, 28 MultipleNCAselect, 28 MultipleNCAselect.BANOVA, 28 MultipleNCAselectdemo, 29 MultipleNCAselectdemo.BANOVA, 29 MultipleNCAselectsave, 29 MultipleNCAselectsave.BANOVA, 29 Multiplentertitle, 29 Multiplentertitle.demo, 30 MultipleParaAIC, 30 MultipleParaAIC.MIX, 30 MultipleParaAICdemo, 31 MultipleParaAICoutput, 31 MultipleParaARS, 31 MultipleParaARS.MIX, 32 MultipleParaARSdemo, 32 MultipleParaARSoutput, 32 MultipleParadata, 33 MultipleParademomenu, 33 MultipleParademomenu1, 33 MultipleParademoMIX, 33 MultipleParamenu, 34 MultipleParaMIX, 34 MultipleParaMIXanalyze, 34 MultipleParaMIXcsv, 34 MultipleParaMIXdata, 35 MultipleParaMIXmenu, 35 MultipleParaMIXoutput, 35 MultipleParaNCA, 35 MultipleParaNCA.MIX, 36 MultipleParaNCA.MIXanalyze, 36 MultipleParaNCA.MIXcsv, 36 MultipleParaNCA.MIXdata, 36 MultipleParaNCA.MIXmenu, 37 MultipleParaNCAanalyze, 37 MultipleParaNCAcsv, 37 MultipleParaNCAdata, 37 MultipleParaNCAdemo, 38 108 INDEX MultipleParaNCAdemo.MIX, 38 MultipleParaNCAoutput, 38 MultipleParaNCAplot, 39 MultipleParaNCAsave, 39 MultipleParaNCAselect, 39 MultipleParaNCAselect.MIX, 39 MultipleParaNCAselectdemo, 39 MultipleParaNCAselectdemo.MIX, 40 MultipleParaNCAselectsave, 40 MultipleParaNCAselectsave.MIX, 40 MultipleParaTTT, 40 MultipleParaTTT.MIX, 41 MultipleParaTTTAIC, 41 MultipleParaTTTAIC.MIX, 42 MultipleParaTTTAICdemo, 42 MultipleParaTTTAICoutput, 43 MultipleParaTTTARS, 43 MultipleParaTTTARS.MIX, 44 MultipleParaTTTARSdemo, 44 MultipleParaTTTARSoutput, 45 MultipleParaTTTdemo, 45 MultipleParaTTToutput, 45 Multipleplotsingle, 46 Multipleplotsingle.para, 46 Multiplestat1menu, 46 Multiplestatmenu, 46 MultipleTTT, 47 MultipleTTT.BANOVA, 47 MultipleTTTAIC, 48 MultipleTTTAIC.BANOVA, 48 MultipleTTTAICdemo, 49 MultipleTTTAICoutput, 49 MultipleTTTARS, 50 MultipleTTTARS.BANOVA, 50 MultipleTTTARSdemo, 51 MultipleTTTARSoutput, 51 MultipleTTTdemo, 52 MultipleTTToutput, 52 NCA, 52 NCA.BANOVA, 53 NCA.BANOVAanalyze, 53 NCA.BANOVAcsv, 53 NCA.BANOVAdata, 53 NCA.BANOVAmenu, 54 NCAanalyze, 54 NCAcsv, 54 NCAdata, 54 NCAdemo, 54 NCAdemo.BANOVA, 55 NCAmenu, 55 NCAoutput, 55 NCAplot, 55 NCAsave, 56 NCAselect, 56 NCAselect.BANOVA, 56 NCAselectdemo, 56 NCAselectdemo.BANOVA, 56 NCAselectsave, 57 NCAselectsave.BANOVA, 57 ParaAIC, 57 ParaAIC.MIX, 57 ParaAICdemo, 58 ParaAICoutput, 58 ParaARS, 58 ParaARS.MIX, 59 ParaARSdemo, 59 ParaARSoutput, 59 Paradata, 60 Parademomenu, 60 Parademomenu1, 60 ParademoMIX, 60 Paralleldata, 61 Paramenu, 61 ParaMIX, 61 ParaMIXanalyze, 61 ParaMIXcsv, 62 ParaMIXdata, 62 ParaMIXmenu, 62 ParaMIXoutput, 62 ParaNCA, 62 ParaNCA.MIX, 63 ParaNCA.MIXanalyze, 63 ParaNCA.MIXcsv, 63 ParaNCA.MIXdata, 63 ParaNCA.MIXmenu, 64 ParaNCAanalyze, 64 ParaNCAcsv, 64 ParaNCAdata, 64 ParaNCAdemo, 64 ParaNCAdemo.MIX, 65 ParaNCAoutput, 65 ParaNCAplot, 65 ParaNCAsave, 65 ParaNCAselect, 66 ParaNCAselect.MIX, 66 ParaNCAselectdemo, 66 INDEX 109 ParaNCAselectdemo.MIX, 66 ParaNCAselectsave, 66 ParaNCAselectsave.MIX, 67 ParaTTT, 67 ParaTTT.MIX, 67 ParaTTTAIC, 68 ParaTTTAIC.MIX, 68 ParaTTTAICdemo, 69 ParaTTTAICoutput, 69 ParaTTTARS, 70 ParaTTTARS.MIX, 70 ParaTTTARSdemo, 71 ParaTTTARSoutput, 71 ParaTTTdemo, 72 ParaTTToutput, 72 plotsingle, 72 plotsingle.para, 72 plotsingle.Rep, 73 prdcount, 73 Repaic, 73 RepAIC.MIX, 73 RepAICdemo, 74 RepAICoutput, 74 RepARS, 74 RepARS.MIX, 75 RepARSdemo, 75 RepARSoutput, 75 Repdemomenu, 76 Repdemomenu1, 76 RepdemoMIX, 76 Replicateddata, 76 Repmenu, 77 RepMIX, 77 RepMIXanalyze, 77 RepMIXcsv, 77 RepMIXdata, 78 RepMIXmenu, 78 RepMIXoutput, 78 RepNCA, 78 RepNCA.MIX, 79 RepNCA.MIXanalyze, 79 RepNCA.MIXcsv, 79 RepNCA.MIXdata, 79 RepNCA.MIXmenu, 80 RepNCAanalyze, 80 RepNCAcsv, 80 RepNCAdata, 80 RepNCAdemo, 80 RepNCAdemo.MIX, 81 RepNCAoutput, 81 RepNCAplot, 81 RepNCAsave, 81 RepNCAselect, 82 RepNCAselect.MIX, 82 RepNCAselectdemo, 82 RepNCAselectdemo.MIX, 82 RepNCAselectsave, 82 RepNCAselectsave.MIX, 83 RepTTT, 83 RepTTT.MIX, 83 RepTTTAIC, 84 RepTTTAIC.MIX, 84 RepTTTAICdemo, 85 RepTTTAICoutput, 85 RepTTTARS, 86 RepTTTARS.MIX, 86 RepTTTARSdemo, 87 RepTTTARSoutput, 87 RepTTTdemo, 88 RepTTToutput, 88 Singlego, 88 sizemenu, 88 stat1menu, 89 statmenu, 89 TotalSingledata, 89 TTT, 89 TTT.BANOVA, 90 TTTAIC, 90 TTTAIC.BANOVA, 91 TTTAICdemo, 91 TTTAICoutput, 92 TTTARS, 92 TTTARS.BANOVA, 93 TTTARSdemo, 93 TTTARSoutput, 94 TTTdemo, 94 TTTdemo.BANOVA, 95 TTToutput, 95 xtick, 95 ytick, 95
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