0 Up votes0 Down votes

3 views109 pagesSep 26, 2014

© © All Rights Reserved

PDF, TXT or read online from Scribd

© All Rights Reserved

3 views

© All Rights Reserved

- The Woman Who Smashed Codes: A True Story of Love, Spies, and the Unlikely Heroine who Outwitted America's Enemies
- Steve Jobs
- NIV, Holy Bible, eBook
- NIV, Holy Bible, eBook, Red Letter Edition
- Hidden Figures Young Readers' Edition
- Cryptonomicon
- Console Wars: Sega, Nintendo, and the Battle that Defined a Generation
- Make Your Mind Up: My Guide to Finding Your Own Style, Life, and Motavation!
- The Golden Notebook: A Novel
- Alibaba: The House That Jack Ma Built
- Hit Refresh: The Quest to Rediscover Microsoft's Soul and Imagine a Better Future for Everyone
- Hit Refresh: The Quest to Rediscover Microsoft's Soul and Imagine a Better Future for Everyone
- Autonomous: A Novel
- The 10X Rule: The Only Difference Between Success and Failure
- Everybody Lies: Big Data, New Data, and What the Internet Can Tell Us About Who We Really Are
- Life After Google: The Fall of Big Data and the Rise of the Blockchain Economy

You are on page 1of 109

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

- tolerance interpretationUploaded byPetur G. Petrov
- Control Chart Constants and Formulas.pdfUploaded bySeparator
- CIVL2111 Assignment 1Uploaded byLatious Lai
- Similarity Factor f2Uploaded byJignesh Patel
- discriminantanalysis-140126075107-phpapp02Uploaded byDigraj Mahanta
- joUploaded byNishaMehta
- Control ChartUploaded byDébora Amaral
- Example Analysis Viability asSayUploaded byPia Lorraine
- Pattern Recognition ClusteringUploaded byMafrur Rischan
- Assignment 1Uploaded bysunnybohra
- TakeHomeSetAUploaded byakshay patri
- Cut Off NumericalUploaded byRaju Panda
- Aldema Rodel StataUploaded byRodel G. Aldema
- Session 3Uploaded byIrfan Raditya Pratama
- Control Chart Constants and FormulasUploaded bySeparator
- statisticsUploaded byMD Jabed Murshed
- Descriptive StatisticsUploaded bydaniel mekonk
- orca_share_media1570016998093 (1)Uploaded byCarl Stephen Abarra
- nullUploaded byapi-25888404
- Laporan StatkomUploaded byAnggun safira
- Geomatematika 2 hnfUploaded byresky_pratama_99Ade
- BAB 3Uploaded bygalih29
- Mama RevisedUploaded byapi-3719928
- Analisis Data MemoriUploaded byBayu Aji Saputra
- panelUploaded bySilver Marvel
- Manual de EstadisticaUploaded byCristián Andrés Pichún Ríos
- Santander Customer Transaction Prediction using R _ .pdfUploaded byShubham Raj
- analysisofcovariance-140715173812-phpapp02.pdfUploaded byKenesa
- fUploaded byAnonymous mc9Kb7L
- Report for Business StatisticsUploaded byPiyush Srivastava

- Brm-chp09Uploaded byRajashekhar B Beedimani
- Data Analyst 1Uploaded byShubham Kumar Kashyap
- 14_Regression2Uploaded byMoldovian Daria
- Data CleaningUploaded byadirosy46
- Tugging on Heartstrings- Shopping Orientation, Mindset, And Consumer Responses to Cause-Related MarketingUploaded bySam Zulueta
- PCX - ReportUploaded byChittesh Sachdeva
- Feature SelectionUploaded byAbdullah Al Imran
- Forecasting Lecture Notes 2 - Introduction to Regression KAUploaded bypneuma110
- 14.5.6 Minitab Time Series and ForecastingUploaded byRiska Prakasita
- The Stata Journal- Promoting Communications on Statistics and Stata Volume 17 Issue 4 2018 [Doi 10.1177_1536867x1801700410] Terza, Joseph v. -- Causal Effect Estimation and Inference Using StataUploaded byHélio Ramos
- HeteroscedasticityUploaded byKarthik Balaji
- Choosing the Right StatisticsUploaded byRomell Ambal Ramos
- Amoore - Life Beyond Big Data Governing With Little AnalyticsUploaded byanton.de.rota
- IEOR E4725 Spring 2016 SyllabusUploaded byzidanex2018
- 2. Forecasting Time SeriesUploaded byRajan Manchanda
- Lec2 Summarising DataUploaded byAjay Bhaarath
- 09 Analysis of Variance- Part1Uploaded byCharlton S.Inao
- Accident and Survey ReportUploaded bypooja doreamon
- CORRELATION ANALYSIS.pptUploaded bysalhotraonline
- Econometrics Assignment HelpUploaded byeconomicshelpdesk
- ATS Course CatalogUploaded byVibish Vijayan
- BBS10 Ppt Mtb Ch13 Simple Linear RegressionUploaded byIrlya Noerofi Tyas
- StudMath 2017-Final UpdatedUploaded byMihai R
- manstatsamplefinalexamUploaded byJhat_28
- ForecastingUploaded byG Murtaza Dars
- proposal.pdfUploaded byMoona Awan
- gmmivUploaded byOntheissues Dot Org
- Addressing-the-Ten-Commonly-Asked-Questions-about-Qualitative-Re.pdfUploaded byChristian Dave Tad-awan
- Complete CRM NotesUploaded byYasmin Inamdar
- Definition of Marketing Research:Uploaded byimad

## Much more than documents.

Discover everything Scribd has to offer, including books and audiobooks from major publishers.

Cancel anytime.