ANMETH is a "record qualifier" according to Model 2.0 so technically we don't need to add the METHOD variable into PP. There would only be one valid value of PPMETHOD anyway = CALCULATION. (Confirm with Fred)
Rows 4-5 can the values in PPANMETH also in PPCAT? (Because PPCAT is blank)
Should ANMETH be only used for named formulas like how LB is using it?
Remove PPMETHOD from PP specification table if decided not needed.
Review suppPP dataset makes sure it looks ok
Do people use PC/PP domain for compartmental analysis data as well? For CT we don’t control none-NCA values, but that’s CT ONLY, on the domain level, do people use PC/PP for None-NCA data anyway? The new term request from GSK asked for a controlled codelist for PKANMETH but the requested value is actually for compartmental analysis – this suggests to me that folks are using PC/PP for compartmental analysis data. Currently the SDTMIG does not explicitly state that users should only represent NCA data in PC/PP. Better understanding this would help to decide whether we should add ANMETH into PP.
The example below shows how to represent various PK analysis parameters at multiple dose, steady state condition.
Rows 1-3:
Show the "AUC from T1 to T2" measurements for Drug Parent (Row 1), Drug Metabolite 1 (Row 2) and Drug Metabolite 2 (Row 3).
Row 4:
Shows the "Ratio AUC" measurement of Drug Metabolite 1 to Drug Parent. Instead of pre-corrdinating "Ratio AUC of Drug Metabolite 1 to Drug Parent" all into the PPTEST, PPANMETH is used to describe the numerator (Drug Metabolite 1) and the denominator (Drug Parent) values that contribute to the Ratio AUC calculation in PPTEST. This post-coordination approach liberates the PPTEST variable from having to house hyper-specific, pre-coordinated PK parameter values.
Row 5:
Shows the "Ratio AUC" measurement of Drug Metabolite 2 to Drug Metabolite 1. Note the PPTEST is Ratio AUC, whereas DRUG METABOLITE 2 TO METABOLITE 1 is in PPANMETH.
Rows 6-7:
Show AUC Infinity Obs and AUC Infinity Pred for the DRUG PARENT. Both are calculated using the LIN-LOG TRAPEZOIDAL METHOD which is in PPANMETH.
pp.xpt
pp.xpt
Row
STUDYID
DOMAIN
USUBJID
PPSEQ
PPRFID
PPTESTCD
PPTEST
PPCAT
PPSCAT
PPORRES
PPORRESU
PPSTRESC
PPSTRESN
PPSTRESU
PPSPEC
PPANMETH
PPFAST
PPNOMDY
PPRFTDTC
1
ABC-123
PP
123-1001
1
B2222
AUCINT
AUC from T1 to T2
DRUG PARENT
NCA
154.1
h*ng/L
154.1
154.1
h*ng/L
PLASMA
Y
1
2001-02-01T12:00
2
ABC-123
PP
123-1001
2
B2222
AUCINT
AUC from T1 to T2
DRUG METABOLITE 1
NCA
144.5
h*ng/L
144.5
144.5
h*ng/L
PLASMA
Y
1
2001-02-01T12:00
3
ABC-123
PP
123-1001
3
B2222
AUCINT
AUC from T1 to T2
DRUG METABOLITE 2
NCA
294.7
h*ng/L
294.7
294.7
h*ng/L
PLASMA
Y
1
2001-02-01T12:00
4
ABC-123
PP
123-1001
4
B2222
RAAUC
Ratio AUC
DRUG METABOLITE 1
NCA
1.07
1.07
1.07
PLASMA
DRUG METABOLITE 1 TO DRUG PARENT
Y
1
2001-02-01T12:00
5
ABC-123
PP
123-1001
5
B2222
RAAUC
Ratio AUC
DRUG METABOLITE 2
NCA
0.52
0.52
0.52
PLASMA
DRUG METABOLITE 2 TO METABOLITE 1
Y
1
2001-02-01T12:00
6
ABC-123
PP
123-1001
1
B2222
AUCIFO
AUC Infinity Obs
DRUG PARENT
NCA
520
h*ng/L
520
520
h*ng/L
PLASMA
LIN-LOG TRAPEZOIDAL METHOD
Y
1
2001-02-01T12:00
7
ABC-123
PP
123-1001
2
B2222
AUCIFP
AUC Infinity Pred
DRUG PARENT
NCA
510
h*ng/L
510
510
h*ng/L
PLASMA
LIN-LOG TRAPEZOIDAL METHOD
Y
1
2001-02-01T12:00
$warningHtml
Dataset Wrapper Debug Message
Please add a row column to your dataset.
The SUPPPP dataset example shows the specific condition under which the PK Analysis was performed.
Addition of a normalized variable flag to capture if a normalization technique was applied either to the source or resultant parameter in the calculation process, this would then need to utilize the accompanying descriptor variable – Variable needed for normalization schemes: body weight, BMI, dose, BSA, molecular weight, etc.
Team decision: we have already gone down the road of pre-coordinating normalization types into the PKPARM-CD values and people are using the published terms. Post-coordinating normalization types into a new variable would require the depreciation of many existing PKPARM terms, this change could be disruptive and costly for the user community to implement and therefore we will not create new variables for normalization types.
Addition of a PP domain variable flag to capture steady state conditions, this could even be expanded into the PC domain as the condition could be considered a state of the source data
Team decision: PK team will create a new variable, tentatively named as “Condition of PK Analysis”, to house values such as Steady State, Single Dose and Multiple-Dose, which will be subject to controlled terminology. Team’s action items are: 1) identify other values that can be controlled for this variable, 2) better define the variable and provide dataset examples.
SD/MD, SD/SS, Parent/Metabolite, Tablet/Capsule, Formula1/Formula2 – all are 2ndary PK analysis based on primary PK parameter results.
Team decision: PK team will create a new variable, tentatively named as “Ratio Label/Raito calculation” to house free-text description of the numerator and denominator values contributing to the ratio calculation described by PKPARM. Action items: 1) PK team to discuss whether one variable is sufficient or should we create separate variables to house the “numerator” and “denominator” values. 2) If two separate variables are created, how should they be named and defined, because “numerator” and “denominator” would only apply when the PKPARM value is a ratio. May want to consider broadening the use and scope of the variables. 3) Provide examples using the proposed variables.
1 Comment
Jordan Li
Decisions Made