Metadata and ADaM.

Transcription

1 Metadata and ADaM 1

2 Disclaimer Any views or opinions presented in this presentation are solely those of the author and do not necessarily represent those of the company. 2

3 Agenda Introduction of ADaM Metadata Clincial Trial Process Examples of how to create Metadata Goal of ADaM Metadata Pros and Cons Conclusion Questions & Answers 3

4 ADaM Metadata Definition Information of ADaM(Analysis Data Model) datasets Types Analysis Dataset Metadata Analysis Variable Metadata Analysis Parameter Value Level Metadata Analysis Results Metadata 4

5 Normal Clinical Trial Process Protocol SAP Mock Up Tables CRF DMDB Raw Derived TFL 5

6 CDISC Clinical Trial Process Protocol SAP Mock Up Tables ecrf ADaM Metadata EDC SDTM ADaM TFL ADaM Related Process 6

7 ADaM Related Process ADaM Metadata Analysis Dataset Metadata Analysis Variable Metadata Analysis Parameter value level Metadata Analysis Results Metadata ADaM TFL 7

8 Example 1 - Time to Event Mock Up table Table Time to Death by Treatment PARAM = Days to Death, TRTP Analysis Population: Intent to Treat ITTFL= Y Drug 1 Drug 2 p-value N xxx xxx Median xx xx x.xx Q1, Q3 xx, xx xx, xx AVAL(Days to Event), CNSR(Censor information) proc lifetest data=adtteos; where PARAM= Days to Death and ITTFL= Y ; time AVAL*CNSR(1); strata TRTP; run; 8

9 Time to Event Analysis Dataset Metadata Dataset Name Dataset Description Dataset Location Dataset Structure Key Variables of Dataset Class of Dataset Documentation ADTTEOS Overall Survival Analysis Dataset adtteos.xpt One record per subject per parameter STUDYID, USUBJID, PARAM BDS adtteos.txt 9

10 [CB1]Note to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S Example 1 : Time to Event Analysis Variable Metadata including Analysis Parameter Value-Level Metadata (1) Dataset Name Parameter Identifier Variable Name Variable Label Variable Type Display Format Codelist / Controlled Terms Source / Derivation ADTTEOS *ALL* STUDYID Study Identifier text $20 ADSL.STUDYID ADTTEOS *ALL* USUBJID Unique Subject Identifier text $20 ADSL.USUBJID ADTTEOS *ALL* ITTFL Intent-To-Treat Population Flag ADTTEOS *ALL* TRTP Planned Treatment ADTTEOS *ALL* TRTPN Planned Treatment (N) text $1 Y, null ADSL.ITTFL text $40 Drug 1, Drug 2 ADSL.TRT01P integer = Drug 1, 2 = Drug 2 ADTTEOS PARAMCD PARAM Parameter text $50 Days to Death ADTTEOS *ALL* PARAMCD Parameter Code text $8 DEATH ADSL.TRT01PN 10

11 [CB1]Note to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S Example 1 : Time to Event Analysis Variable Metadata including Analysis Parameter Value-Level Metadata (2) Dataset Name Parameter Identifier Variable Name Variable Label Variable Type Display Format Codelist / Controlled Terms Source / Derivation ADTTEOS *ALL* AVAL Analysis Value float 8.2 ADT STARTDT + 1 ADTTEOS *ALL* STARTDT Time to Event Origin Date for Subject integer YYYYMM DD10. ADTTEOS *ALL* ADT Analysis Date integer YYYYMM DD10. ADSL.RANDDT SAS Date of DS.DSDTC ADTTEOS *ALL* CNSR Censor integer 1.0 0, 1 0 for DS.DSDECOD = DEATH, 1 for any other study completion ADTTEOS *ALL* EVNTDESC Event or Censoring Description text $40 DEATH, COMPLETED THE STUDY, LOST TO FOLLOW-UP, AE, PD DS.DSDECOD 11

12 [CB1]Note to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S Example 1 : Time to Event ADaM Dataset USUBJID TRTP PARAM AVAL STARTDT ADT CNSR EVNTDESC Study Drug 1 Days to Death Study Drug 2 Days to Death Study Drug 2 Days to Death Study Drug 1 Days to Death COMPLETED THE STUDY AE DEATH PD 12

13 Example 1 : Time to Event Analysis Results Metadata Metadata Field DISPLAY IDENTIFIER DISPLAY NAME RESULT IDENTIFIER PARAM PARAMCD ANALYSIS VARIABLE REASON DATASET SELECTION CRITERIA DOCUMENTATION PROGRAMMING STATEMENTS Table Metadata Time to Death by Treatment, Analysis Population: Intent to Treat Days to Death Days to Death DEATH AVAL Primary efficacy analysis ADTTEOS ITTFL= Y and PARAM = Days to Death See SAP Section XX for details. Program: t death.txt proc lifetest data= ADTTEOS; where ITTFL= Y and PARAM = Days to Death ; time AVAL*CNSR(1); strata TRTP; run; 13

14 Example 2 : Time to Event Mock Up table Table Time to Progression Free Survival : Cox Proportional Hazard Model PARAM = Days to Progression Free Survival, TRTP Analysis Population: Intent to Treat ITTFL= Y Drug 1 Drug 2 p-value N xxx xxx Median xx xx x.xx Q1, Q3 xx, xx xx, xx AVAL(Days to Event), CNSR(Censor information) proc phreg data=adtteos; where PARAM= Days to Progression Free Survival and ITTFL= Y ; model AVAL*CNSR(1) = TRTP AGE SEX ; run; 14

15 [CB1]Note to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S Example 2 : Time to Event Analysis Variable Metadata including Analysis Parameter Value-Level Metadata (1) Dataset Name Parameter Identifier Variable Name Variable Label Variable Type Display Format PFS Codelist / Controlled Terms Source / Derivation ADTTEOS *ALL* STUDYID Study Identifier text $20 ADSL.STUDYID ADTTEOS *ALL* USUBJID Unique Subject Identifier text $20 ADSL.USUBJID ADTTEOS *ALL* AGE Age integer 3.0 ADSL.AGE ADTTEOS *ALL* SEX Sex text $1 ADSL.SEX ADTTEOS *ALL* ITTFL Intent-To-Treat Population Flag text $1 Y, null ADSL.ITTFL ADTTEOS *ALL* TRTP Planned Treatment ADTTEOS *ALL* TRTPN Planned Treatment (N) text $40 Drug 1, Drug 2 ADSL.TRT01P integer = Drug 1, 2 = Drug 2 ADTTEOS PARAMCD PARAM Parameter text $50 Days to Death Days to Progression Free Survival ADTTEOS *ALL* PARAMCD Parameter Code text $8 DEATH ADSL.TRT01PN 15

16 Example 2 : Time to Event Analysis Variable Metadata including Analysis Parameter Value-Level Metadata (2) Dataset Name Parameter Identifier Variable Name Variable Label Variable Type Display Format Codelist / Controlled Terms Source / Derivation ADTTEOS *ALL* AVAL Analysis Value float 8.2 ADT STARTDT + 1 ADTTEOS *ALL* STARTDT Time to Event Origin Date for Subject integer YYYYMM DD10. ADTTEOS *ALL* ADT Analysis Date integer YYYYMM DD10. ADSL.RANDDT SAS Date of DS.DSDTC ADTTEOS DEATH CNSR Censor integer 1.0 0, 1 0 for DS.DSDECOD = DEATH, 1 for any other study completion ADTTEOS PFS CNSR Censor integer 1.0 0, 1 0 for DS.DSDECOD in( DEATH, PD ), 1 for any other study completion ADTTEOS *ALL* EVNTDESC Event or Censoring Description text $40 DEATH, COMPLETED THE STUDY, LOST TO FOLLOW-UP, AE, PD DS.DSDECOD 16

17 [CB1]Note to ADaM team: We have elected to use this format for the program names. According to the Study Data Specifications, since the programs created by S Example 2 : Time to Event ADaM Dataset USUBJ ID AGE SEX TRTP PARAM AVA L 43 M Study Drug 1 57 F Study Drug 2 71 M Study Drug 2 55 F Study Drug 1 43 M Study Drug 1 57 F Study Drug 2 71 M Study Drug 2 55 F Study Drug 1 STAR TDT Days to Death Days to Death Days to Death Days to Death Days to Progression Free Survival Days to Progression Free Survival Days to Progression Free Survival Days to Progression Free Survival ADT CNSR EVNTDESC COMPLETED THE STUDY 1 AE 0 DEATH 1 PD 1 COMPLETED THE STUDY 1 AE 0 DEATH 0 PD 17

18 Example 2 : Time to Event Analysis Results Metadata Metadata Field DISPLAY IDENTIFIER DISPLAY NAME RESULT IDENTIFIER PARAM PARAMCD ANALYSIS VARIABLE REASON DATASET SELECTION CRITERIA DOCUMENTATION PROGRAMMING STATEMENTS Table Metadata Time to Progression Free Survival : Cox Proportional Hazard Model Days to Progression Free Survival Days to Progression Free Survival PFS AVAL Secondary efficacy analysis ADTTEOS ITTFL= Y and PARAM= Days to Progression Free Survival See SAP Section XX for details. Program: t pfs.txt proc phreg data= ADTTEOS; run; where ITTFL= Y and PARAM = Days to Progression Free Survival ; model AVAL*CNSR(1) = TRTP AGE SEX; 18

19 Summary of Examples Mock Up Tables ADaM Metadata Dataset ADTTEOS Variables STUDYDI, USUBJID ITTFL TRTP, TRTPN PARAM, PARAMCD AVAL STARTDT, ADT CNSR EVNTDESC AGE SEX Parameter DEATH PFS Results Days to Death Days to Progression Free Survival 19

20 Goal of Metadata Serve as Spec and Define Spec : provide the programmers how ADaM and some TFL can be created Define : datasets information for sponsors Central document for all programmers and statisticians 20

21 Goal of Metadata (2) Minimize the communication traffic in virtual office setting Philadelphia Office Boston Office India Office Remote Programming Reconciliation between ADaM datasets and Metadata use macros to check wether ADaM datasets follow ADaM Metadata. 21

22 Cons Who will prepare and maintain the metadata CDISC expert(sdtm, ADaM and so on) Programmer Lead Statistician The initial investment on resource and time at the early stage of the study Two many metadata? 22

23 Pros (1) Consistency in ADaM datasets Label Name Format # of variables Help the inexperience personnel ADaMis new The central document between developers and validators especially for the virtual office setting Helps the programmers on efficacy analysis. 23

24 Pros (2) Better estimate on the number of ADaM datasets help the planning and resourcing. Review on Mock Up tables and SAP 24

25 Conclusion The concept of Metadata is Plan your work and work your plan ADaM Metadata is ongoing until all are done. 25

26 Questions? 26