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Copyright © 2009 Phase Forward Incorporated. All rights reserved. Roger Landau Principal Consultant, Lincoln Safety Group, Phase Forward 10 Sep 2009 Converting.

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Presentation on theme: "Copyright © 2009 Phase Forward Incorporated. All rights reserved. Roger Landau Principal Consultant, Lincoln Safety Group, Phase Forward 10 Sep 2009 Converting."— Presentation transcript:

1 Copyright © 2009 Phase Forward Incorporated. All rights reserved. Roger Landau Principal Consultant, Lincoln Safety Group, Phase Forward 10 Sep 2009 Converting Pharmacokinetic Data to the PP and PC Domains

2 Introduction  Support for Pharmacokinetic (PK) data new in SDTM  PK data combines CRF timing variables Lab findings Derived data  Converting to SDTM can be difficult  Will present my recommendations  Interactive participation encouraged 2

3 Overview  Typical Pharmacokinetic Data Workflow  Logical Data Model  SDTM Data Model  Recommendations for converting data Use of RELREC 3

4 Typical Pharmacokinetic Data Workflow 4 ………………………………………………………………………………………………………………………..

5 PK Data  Consists of two types of data 1)Concentration of drug or metabolite in bodily fluid/substance  Analyte – drug or metabolic product whose concentration is analyzed in biologic matrix  Parent compound or metabolite produced when body metabolizes compound  Biological Matrix – fluid or substance in a living being  Usually plasma or urine  Can also be feces, Cerebrospinal Fluid (CSF) 5

6 PK Data 2) PK Parameters Derived values describing how a compound is metabolized by the body over time – T 1/2 : Half-life – AUC: Area Under the Curve – C Max: maximum concentration – T Max: time from drug administration to maximum concentration – Many others

7 Phase I Crossover Studies  PK analysis usually in phase I crossover studies.  Some studies only include concentration  No PK parameters  In each period/epoch:  Blood samples taken at many timepoints  Urine collected over several intervals 7

8 Typical PK Data Workflow 8 Bioanalytical Lab Clinical DB Management System Concentration Results CRF Timepoints Merged Concentration Data Clinical Study Report Statistical Analysis Biostatistics Pharmacokineticist PK Parameters WinNonLin Issues: Three different data sources Three different departments Three different systems No data standards

9 Logical Data Model 9 ………………………………………………………………………………………………………………………..

10 Logical Data Model  Three entities Two SDTM domains PC and PP  Relationships CRF-Timepoints to Concentration – One-to-many Concentration to PK Parameters – Many-to-many – Requires use of RELREC in SDTM

11 SDTM Data Model 11 ………………………………………………………………………………………………………………………..

12 SDTM PK Data Model  Two domains PC – Concentration Data PP – PK Parameters  Both are Findings domains PC has more timing and qualifier variables  PC and PP related to one another But relationship is complex

13 PC Domain

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16 PP Domain

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18 Recommendations for Converting PK Data 18 ………………………………………………………………………………………………………………………..

19 Converting PK Data - Recommendations  Source Data May be in different formats: XPT, XLS, TXT May be one PK file per analyte CRF Timepoint and Concentration may be in separate files – Merging/joining will probably not go smoothly Accession number typos, missing records, etc. Usually will need to join and/or concatenate datasets before converting  Analyte Maps to different variables in PP and PC Compound/metabolite names may be spelled inconsistently in different datasets

20 Converting PK Data - Recommendations  Units Can be different for different analytes: – pg/ml – ng/ml Some PK parameters don’t have units – No of points – R-squared  PK Parameter Test Codes Develop library of PPTEST and PPTESTCD Work with Pharmacokineticists Encourage use of standard PPTESTCDs in WinNonLin

21 Converting PK Data - Recommendations  Status Flags Useful for statistical analysis and relationship between PP and PC Obtain flags in WinNonLin output indicating values not to be used in analysis May be difficult to obtain due to WinNonLin shortcomings  Epoch Include Epoch variable in PC and PP Represents Period in crossover Frequently included in source data

22 Relating PP to PC  Each PK Parameter in PP calculated from set of concentrations in PC  PP and PC can be joined to show related values  Implementation Guide Analysis datasets may document relationship OR RELREC used to represent how to join PP and PC  RELREC method will be discussed

23 IG – Section  Relating PP Records to PC Records  Reading this section of IG will either Make you head spin Put you to sleep

24 Logical Data Model  Many-to-Many relationship Each PK parameter calculated from several concentrations Each Concentration used in the calculation of several PK parameters  RELREC provides data needed to perform many- to-many join

25 RELREC  Can be used in one of two methods Relating Datasets (simpler) Relating Records (more complex)

26 RELREC - Relating Datasets  Can only be used if: For all subjects All concentrations at all timepoints used for all PK parameters  PCGPRID, PPGRPID = Matrix + Analyte + Period  This situation usually doesn’t happen Some values excluded  Acceptable if agreed that excluded values do not need to be identified in SDTM datasets

27 RELREC – Relating Records  Populate RELREC with records from both PP and PC Use RELID to indicate related records  IG provides 4 examples (1, 2, 3, 4)  For each example, 4 possible methods (A, B, C, D) to populate RELREC  OMG! Less would have been more

28 RELREC – Relating Records Recommendations  Only use Method A Use PCGRPID and PPGRPID as IDVARs in RELREC  Set PPGRPID and PCGRPID to Matrix + Analyte + Period PPGRPID = PPSPEC + PPCAT + EPOCH PCGRPID = PCSPEC + PCTEST + EPOCH

29 RELREC – Relating Records Recommendations  Use example 2 method to indicate concentration values not used in PK parameter calculations. Usually due to insufficient sample or subject vomited Can be obtained from PCSPCCND and PCSTAT/PCREASND

30 RELREC – Relating Records Recommendations (cont’d)  Do not indicate concentration values not used to calculate particular PK parameters Examples 3 and 4 in IG Documents Pharmacokineticist’s analytical methods Information in WinNonLin Difficult to obtain and document Not appropriate in SDTM tabulation datasets  Has any one used any of these methods? Which method was used? How did it work out?

31 Summary  Converting PK data to PP and PC can be challenging Source data from three different systems  PC and PP follow Findings model Several complexities need to be taken into account  Recommendations listed for converting source data to SDTM  Relating PP to PC using RELREC Use Method A and example 2 from IG

32 32 Thank You © 2009 Phase Forward Incorporated. All rights reserved.


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