Implementation of CDISC ADAM in The Pharmacokinetics Department
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Transcript of Implementation of CDISC ADAM in The Pharmacokinetics Department
![Page 1: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/1.jpg)
IMPLEMENTATION OF CDISC ADAM IN
THE PHARMACOKINETICS DEPARTMENT
Presented by Joanna Magielse, SGS Life Science Services
![Page 2: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/2.jpg)
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OUTLINE
Introduction
Gain
Pharmacokinetic analysis
Conclusion
![Page 3: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/3.jpg)
3
OUTLINE
Introduction
Gain
Pharmacokinetic analysis
Conclusion
![Page 4: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/4.jpg)
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INTRODUCTION
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
![Page 5: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/5.jpg)
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OUTLINE
Introduction
Gain
Pharmacokinetic analysis
Conclusion
![Page 6: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/6.jpg)
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Standardization
Efficiency
Time
Efficiency
PK
STAT
•
STAT
• ADaM
DM
•
DM
• SDTM
GAIN
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OUTLINE
Introduction
Gain
Pharmacokinetic analysis
Conclusion
![Page 8: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/8.jpg)
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PHARMACOKINETIC ANALYSIS
Protocol:
Pharmacokinetic parameters: Cmax tmax t1/2 AUClst AUCifo
AV
AL
(ng
/mL
)
ARELTM2
(h)
Cmax
tmax
Slope for t1/2
AUCifo
• Min 3 points
after Cmax
• R²adj>0.9
• Only if t1/2
can be
estimated
AV
AL
(ng
/mL
)
ARELTM2
(h)
AVAL: Analysis value
ARELTM: Analysis relative time
AUClst
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 9: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/9.jpg)
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PHARMACOKINETIC ANALYSIS
Statistical Analysis Plan
PK population
Handling of data
Statistical analysis
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 10: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/10.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 11: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/11.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 12: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/12.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 13: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/13.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 14: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/14.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 15: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/15.jpg)
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PHARMACOKINETIC ANALYSIS
Statistical Analysis Plan
Statistical analysis:
• AUCpeo > 20% => exclude AUCifo from statistical
analysis
AUCifo
AV
AL
(ng
/mL
)
ARELTM2
(h)
AUClst A
VA
L
(ng
/mL
)
ARELTM2
(h)
AUCpeo: AUC %extrapolation
AUCifo: AUC infinity
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 16: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/16.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 17: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/17.jpg)
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PHARMACOKINETIC ANALYSIS
Database lock
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 18: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/18.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 19: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/19.jpg)
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PHARMACOKINETIC ANALYSIS
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
![Page 20: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/20.jpg)
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In SAS
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
![Page 21: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/21.jpg)
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CREATION OF ADPC
Analysis variable metadata
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
SDTM
ADAM
PK
ADAM
![Page 22: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/22.jpg)
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CREATION OF ADPC
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
![Page 23: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/23.jpg)
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CREATION OF ADPC
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
![Page 24: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/24.jpg)
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CREATION OF ADPC
PARAM, PARAMCD
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CREATION OF ADPC
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
![Page 26: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/26.jpg)
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CREATION OF ADPC
ADTM
Character Numeric
SAS format:
is8601dt.
![Page 27: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/27.jpg)
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CREATION OF ADPC
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
![Page 28: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/28.jpg)
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CREATION OF ADPC
AVISIT, AVISITN
![Page 29: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/29.jpg)
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CREATION OF ADPC
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
![Page 30: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/30.jpg)
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CREATION OF ADPC
ATPT, ATPTN
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 31: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/31.jpg)
31
CREATION OF ADPC
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
![Page 32: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/32.jpg)
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CREATION OF ADPC
ARELTM, ARELMTU, ANCHOR
![Page 33: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/33.jpg)
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CREATION OF ADPC
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
![Page 34: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/34.jpg)
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CREATION OF ADPC
ANLzzFL, ANLzzFD
![Page 35: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/35.jpg)
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CREATION OF ADPC
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 36: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/36.jpg)
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CREATION OF ADPC
Missing predose => 0
![Page 37: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/37.jpg)
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CREATION OF ADPC
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/38.jpg)
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CREATION OF ADPC
BLoQ => 0
BLoQ: Below Limit of Quantification
![Page 39: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/39.jpg)
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CREATION OF ADPC
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/40.jpg)
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CREATION OF ADPC
Embedded BLoQ
BLoQ: Below Limit of Quantification
![Page 41: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/41.jpg)
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CREATION OF ADPC
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/42.jpg)
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CREATION OF ADPC
Time deviation
![Page 43: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/43.jpg)
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CREATION OF ADPC
Predose >5% Cmax
![Page 44: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/44.jpg)
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PHARMACOKINETIC ANALYSIS
ADPC is imported in Phoenix® WinNonLin
Include observations for analysis:
ANL01FL = ‘Y’
PK analysis:
Time: ARELTM2
Conc: AVAL
Output file: PK parameters
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 45: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/45.jpg)
45
CREATION OF PP
In SAS
Add and rename variables (SDTM IG):
DOMAIN PPSEQ PPCAT PPSPEC
Calculate extra PK parameters:
e.g. Ratio of metabolite/parent AUC
PPTEST, PPTESTCD:
Controlled terminology
Relation with PC:
PPRFTDTC
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 46: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/46.jpg)
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CREATION OF PP
R²adj < 0.9
AV
AL
(ng
/mL
)
ARELTM2
(h)
![Page 47: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/47.jpg)
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CREATION OF ADPP
In SAS
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/48.jpg)
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CREATION OF ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/49.jpg)
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CREATION OF ADPP
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
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CREATION OF ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/51.jpg)
51
CREATION OF ADPP
PARAM, PARAMCD
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52
CREATION OF ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/53.jpg)
53
CREATION OF ADPP
AVISIT, AVISITN
![Page 54: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/54.jpg)
54
CREATION OF ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/55.jpg)
55
CREATION OF ADPP
ANLzzFL, ANLzzFD
![Page 56: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/56.jpg)
56
CREATION OF ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/57.jpg)
57
CREATION OF ADPP
AVAL = PPSTRESN
![Page 58: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/58.jpg)
58
CREATION OF ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/59.jpg)
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CREATION OF ADPP
AUCpeo > 20% AUCifo
AV
AL
(ng
/mL
)
ARELTM2
(h)
![Page 60: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/60.jpg)
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STATISTICAL ANALYSIS
ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/61.jpg)
61
TABLES, LISTINGS AND FIGURES
ADPC
ADPP
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 ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/62.jpg)
62
TABLES, LISTINGS AND FIGURES
ADPC
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 63: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/63.jpg)
63
TABLES, LISTINGS AND FIGURES
ADPP
SDTM
ADaM
ADPC
PK analysis
PP
ADPP
STAT
OUTPUT
SAP
DB lock
Protocol
CSR
![Page 64: Implementation of CDISC ADAM in The Pharmacokinetics Department](https://reader034.fdocuments.us/reader034/viewer/2022050708/55835d63d8b42a3e1d8b5353/html5/thumbnails/64.jpg)
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OUTLINE
Introduction
Gain
Pharmacokinetic analysis
Conclusion
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CONCLUSION
ADPC/ADPP
SDTM + ADaM
Derived variables
• Based on BDS
• Modified variables (ANLzzFD, ARELTM1, ARELTM2)
PK analysis
ARELTM2 and AVAL
Selection observations
ANLzzFL
Data handling
CRITy
Guidance from CDISC needed
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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