implementation of cdisc ada in the …" pharmacokinetic parameters: c max t max t 1/2 auc lst...
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![Page 1: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/1.jpg)
IMPLEMENTATION OF CDISC ADAM IN THE PHARMACOKINETICS DEPARTMENT Presented by Joanna Magielse, SGS Life Science Services
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OUTLINE
n Introduction
n Gain
n Pharmacokinetic analysis
n Conclusion
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OUTLINE
n Introduction
n Gain
n Pharmacokinetic analysis
n Conclusion
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INTRODUCTION
n Steps of PK study: § Protocol § Statistical Analysis Plan § Database Lock
• SDTM datasets • ADaM datasets
§ Creation of ADPC dataset § PK analysis § Creation of PP dataset § Creation of ADPP dataset § Statistical analysis § Creation Tables, Listings, Figures § Clinical report
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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OUTLINE
n Introduction
n Gain
n Pharmacokinetic analysis
n Conclusion
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n Standardization
⇒ Efficiency ↑
⇒ Time ↓
Efficiency ↑
PK
STAT • ADaM
DM • SDTM
GAIN
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OUTLINE
n Introduction
n Gain
n Pharmacokinetic analysis
n Conclusion
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PHARMACOKINETIC ANALYSIS
n Protocol: § Pharmacokinetic parameters: Cmax tmax t1/2 AUClst AUCifo
AVA
L (n
g/m
L)
ARELTM2 (h)
Cmax
tmax
Slope for t1/2
AUCifo
• Min 3 points after Cmax • R²adj>0.9
• Only if t1/2 can be estimated
AVA
L (n
g/m
L)
ARELTM2 (h)
AVAL: Analysis value ARELTM: Analysis relative time
AUClst
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § PK population § Handling of data § Statistical analysis
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § PK population
• Co medication: § Drug/drug interactions § Drug with motility interference
• Adverse events: § Vomiting / diarrhea
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § Handling of data:
• If predose missing => AVAL = 0 for PK analysis
AVAL: Analysis Value
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § Handling of data:
• If BLoQ => AVAL = 0
BLoQ: Below Limit of Quantification AVAL: Analysis Value
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § Handling of data:
• If embedded BLoQ => exclude from PK analysis
BLoQ: Below Limit of Quantification
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § Handling of data:
• Time deviations >10% => exclude from descriptive statistics
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § Statistical analysis:
• AUCpeo > 20% => exclude AUCifo from statistical analysis
AUCifo
AVA
L (n
g/m
L)
ARELTM2 (h)
AUClst AV
AL
(ng/
mL)
ARELTM2 (h)
AUCpeo: AUC %extrapolation AUCifo: AUC infinity
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n Statistical Analysis Plan § Statistical analysis:
• Bioequivalence studies: If quantifiable concentration at pre-dose > 5% Cmax => subject will be excluded
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
Database lock SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n SDTM datasets § DM (Demographics) § EX (Exposure) § PC (Pharmacokinetic concentrations) § CM (Concomitant medications) § AE (Adverse events) § DV (Protocol deviations) § CO (Comments)
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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PHARMACOKINETIC ANALYSIS
n ADaM datasets § ADSL (Subject-level Analysis Dataset) § ADAPER (Subject Analysis periods Dataset) § (ADEX) (Analysis Dataset containing Exposure Data)
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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n In SAS
n Based upon define.xml
CREATION OF ADPC
ADPC ADSL ADAPER
EX PC
Add. variables
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
SDTM
ADAM
PK
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CREATION OF ADPC
n Analysis variable metadata
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
SDTM
ADAM
PK
ADAM
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CREATION OF ADPC
n Additional/derived variables: BDS § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD
• PARAM: based upon PCTEST and PCSTRESU • PARAMCD: abbreviation • PARAMN: numeric version of PARAM
§ ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n PARAM, PARAMCD
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM
• Derived from PCDTC • ASTDTM and AENDTM: in case of interval (e.g.
urine) § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n ADTM
Character Numeric SAS format:
is8601dt.
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN
• Derived from VISIT and VISITNUM • PK conc that refer to same exposure
§ ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n AVISIT, AVISITN
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN
• Derived from PCTPT and PCTPTNUM § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n ATPT, ATPTN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR
• ANCHOR: EXSTDTC / PCRFTDTC / PCDTC / ADTM • ARELTM1: PCDTC – EXSTDTC • ARELTM2: if ARELTM1 < 0 (predose): ARELTM2 = 0
others: ARELTM2 = ARELTM1 § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n ARELTM, ARELMTU, ANCHOR
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD
• Select set of records for analysis: § PK analysis § Descriptive statistics § Inferential statistical analysis § Steady state analysis
§ AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n ANLzzFL, ANLzzFD
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD
§ ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC
• AVAL= PCSTRESN § Missing predose: AVAL = 0 § BLoQ: AVAL = 0 § Embedded BLoQ: exclude from PK analysis
§ CRITy, CRITyFL, CRITyFN
BLoQ: Below Limit of Quantification
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
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CREATION OF ADPC
n Missing predose => 0
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CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC
• AVAL= PCSTRESN § Missing predose: AVAL = 0 § BLoQ: AVAL = 0 § Embedded BLoQ: exclude from PK analysis
§ CRITy, CRITyFL, CRITyFN
BLoQ: Below Limit of Quantification
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 38: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/38.jpg)
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CREATION OF ADPC
n BLoQ => 0
BLoQ: Below Limit of Quantification
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39
CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC
• AVAL= PCSTRESN § Missing predose: AVAL = 0 § BLoQ: AVAL = 0 § Embedded BLoQ: exclude from PK analysis
§ CRITy, CRITyFL, CRITyFN
BLoQ: Below Limit of Quantification
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 40: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/40.jpg)
40
CREATION OF ADPC
n Embedded BLoQ
BLoQ: Below Limit of Quantification
![Page 41: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/41.jpg)
41
CREATION OF ADPC
n Additional/derived variables § PARAM, PARAMN, PARAMCD § ADTM, ASTDTM, AENDTM § AVISIT, AVISITN § ATPT, ATPTN § ARELTM, ARELTMU, ANCHOR § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
• Criteria evaluation § Time deviation > 10% § Predose > 5% Cmax (cross over studies)
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 42: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/42.jpg)
42
CREATION OF ADPC
n Time deviation
![Page 43: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/43.jpg)
43
CREATION OF ADPC
n Predose >5% Cmax
![Page 44: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/44.jpg)
44
PHARMACOKINETIC ANALYSIS
n ADPC is imported in Phoenix® WinNonLin
n Include observations for analysis: § ANL01FL = ‘Y’
n PK analysis: § Time: ARELTM2 § Conc: AVAL
n Output file: PK parameters
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 45: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/45.jpg)
45
CREATION OF PP
n In SAS
n Add and rename variables (SDTM IG): § DOMAIN PPSEQ PPCAT PPSPEC
n Calculate extra PK parameters: § e.g. Ratio of metabolite/parent AUC
n PPTEST, PPTESTCD: § Controlled terminology
n Relation with PC: § PPRFTDTC
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 46: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/46.jpg)
46
CREATION OF PP
n R²adj < 0.9
AVA
L (n
g/m
L)
ARELTM2 (h)
![Page 47: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/47.jpg)
47
CREATION OF ADPP
n In SAS
n Based upon define.xml
ADSL ADAPER
PP
Add. variables
ADPP
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
SDTM
ADAM
PK
![Page 48: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/48.jpg)
48
CREATION OF ADPP
n Analysis variable metadata
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
SDTM
ADAM
ADAM
PK
![Page 49: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/49.jpg)
49
CREATION OF ADPP
n Additional/derived variables: BDS § PARAM, PARAMN, PARAMCD § AVISIT, AVISITN § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 50: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/50.jpg)
50
CREATION OF ADPP
n Additional/derived variables § PARAM, PARAMN, PARAMCD
• PARAM: PK parameter with unit • PARAMCD: abbreviation • PARAMN: numeric version of PARAM
§ AVISIT, AVISITN § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 51: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/51.jpg)
51
CREATION OF ADPP
n PARAM, PARAMCD
![Page 52: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/52.jpg)
52
CREATION OF ADPP
n Additional/derived variables § PARAM, PARAMN, PARAMCD § AVISIT, AVISITN
• Analogue to AVISIT in ADPC § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 53: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/53.jpg)
53
CREATION OF ADPP
n AVISIT, AVISITN
![Page 54: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/54.jpg)
54
CREATION OF ADPP
n Additional/derived variables § PARAM, PARAMN, PARAMCD § AVISIT, AVISITN § ANLzzFL, ANLzzFD
• Select set of records for analysis: § Statistical analysis § Descriptive statistics
§ AVAL, AVALC § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 55: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/55.jpg)
55
CREATION OF ADPP
n ANLzzFL, ANLzzFD
![Page 56: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/56.jpg)
56
CREATION OF ADPP
n Additional/derived variables § PARAM, PARAMN, PARAMCD § AVISIT, AVISITN § ANLzzFL, ANLzzFD § AVAL, AVALC
• AVAL = PPSTRESN § CRITy, CRITyFL, CRITyFN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 57: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/57.jpg)
57
CREATION OF ADPP
n AVAL = PPSTRESN
![Page 58: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/58.jpg)
58
CREATION OF ADPP
n Additional/derived variables § PARAM, PARAMN, PARAMCD, PARAMTYP § AVISIT, AVISITN § ANLzzFL, ANLzzFD § AVAL, AVALC § CRITy, CRITyFL, CRITyFN
• Criteria evaluation § AUCpeo > 20%
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 59: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/59.jpg)
59
CREATION OF ADPP
n AUCpeo > 20% AUCifo
AVA
L (n
g/m
L)
ARELTM2 (h)
![Page 60: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/60.jpg)
60
STATISTICAL ANALYSIS
n ADPP
n Include observations from inferential statistical analysis: § ANL01FL = ‘Y’
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 61: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/61.jpg)
61
TABLES, LISTINGS AND FIGURES
n ADPC
n ADPP
n Include observations from descriptive statistical analysis: § ANL02FL = ‘Y’
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 62: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/62.jpg)
62
TABLES, LISTINGS AND FIGURES
n ADPC
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 63: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/63.jpg)
63
TABLES, LISTINGS AND FIGURES
n ADPP
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 64: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/64.jpg)
64
OUTLINE
n Introduction
n Gain
n Pharmacokinetic analysis
n Conclusion
![Page 65: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/65.jpg)
65
CONCLUSION
n ADPC/ADPP § SDTM + ADaM § Derived variables
• Based on BDS • Modified variables (ANLzzFD, ARELTM1, ARELTM2)
n PK analysis § ARELTM2 and AVAL
n Selection observations § ANLzzFL
n Data handling § CRITy
n Guidance from CDISC needed
![Page 66: IMPLEMENTATION OF CDISC ADA IN THE …" Pharmacokinetic parameters: C max t max t 1/2 AUC lst AUC ifo (ng / mL) ARELTM2 (h) C max t max (h) Slope for t 1/2 AUC ifo • Min 3 points](https://reader030.vdocuments.net/reader030/viewer/2022040109/5e4ba3fdb1c69b206221f63a/html5/thumbnails/66.jpg)
66
THANK YOU FOR YOUR ATTENTION
Joanna Magielse Life Science Services Pharmacokineticist SGS Belgium NV Vieux Chemin du Poète10 1301 Wavre - Belgium Phone: + 32(0)15 44 01 33 Email: [email protected]
WHERE EXPERIENCE MEETS SPEED