• Fill in results and units for rows 6 and 7
  • Fill in PKCOND values for rows 6 and 7
  • 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

RowSTUDYIDDOMAINUSUBJIDPPSEQPPRFIDPPTESTCDPPTESTPPCATPPSCATPPORRESPPORRESUPPSTRESCPPSTRESNPPSTRESUPPSPECPPANMETHPPFASTPPNOMDYPPRFTDTC
1ABC-123PP123-10011B2222

AUCINT

AUC from T1 to T2DRUG PARENTNCA154.1h*ng/L154.1154.1h*ng/LPLASMA
Y12001-02-01T12:00
2ABC-123PP123-10012B2222

AUCINT

AUC from T1 to T2DRUG METABOLITE 1NCA144.5h*ng/L144.5144.5h*ng/LPLASMA
Y12001-02-01T12:00
3ABC-123PP123-10013B2222AUCINTAUC from T1 to T2DRUG METABOLITE 2NCA294.7h*ng/L294.7294.7h*ng/LPLASMA
Y12001-02-01T12:00
4ABC-123PP123-10014B2222RAAUCRatio AUCDRUG METABOLITE 1NCA1.07
1.071.07
PLASMADRUG METABOLITE 1 TO DRUG PARENTY12001-02-01T12:00
5ABC-123PP123-10015B2222RAAUCRatio AUCDRUG METABOLITE 2NCA0.52
0.520.52
PLASMADRUG METABOLITE 2 TO METABOLITE 1Y12001-02-01T12:00
6ABC-123PP123-10011B2222AUCIFOAUC Infinity ObsDRUG PARENTNCA520h*ng/L520520h*ng/LPLASMALIN-LOG TRAPEZOIDAL METHODY1

2001-02-01T12:00

7ABC-123PP123-10012B2222AUCIFPAUC Infinity PredDRUG PARENTNCA510h*ng/L510510h*ng/LPLASMALIN-LOG TRAPEZOIDAL METHODY1

2001-02-01T12:00

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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.

pp.xpt

supppp.xpt

RowSTUDYIDDOMAINUSUBJIDIDVARIDVARVALQNAMQLABELQVALQORIGQEVAL
1ABC-123PP123-1001PPSEQ1PKCONDCondition of PK AnalysisMULTIPLE DOSE, STEADY STATEeDT
2ABC-123PP123-1001PPSEQ2PKCONDCondition of PK AnalysisMULTIPLE DOSE, STEADY STATEeDT
3ABC-123PP123-1001PPSEQ3PKCONDCondition of PK AnalysisMULTIPLE DOSE, STEADY STATEeDT
4ABC-123PP123-1001PPSEQ4PKCONDCondition of PK AnalysisMULTIPLE DOSE, STEADY STATEeDT
5ABC-123PP123-1001PPSEQ5PKCONDCondition of PK AnalysisMULTIPLE DOSE, STEADY STATEeDT
6ABC-123PP123-1001PPSEQ6PKCONDCondition of PK AnalysisMULTIPLE DOSE, STEADY STATEeDT
7ABC-123PP123-1001PPSEQ7PKCONDCondition of PK AnalysisSINGLE DOSEeDT
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1 Comment

  1. Decisions Made

    1. 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.
      1. 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.

     

    1. 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
      1. 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.

     

    1. SD/MD, SD/SS, Parent/Metabolite, Tablet/Capsule, Formula1/Formula2 – all are 2ndary PK analysis based on primary PK parameter results.
      1. 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.