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SDTM AND ADaM:HANDS-ON SOLUTIONSCDISC French Speaking User GroupParis, France17 February 2012
Joris De Bondt, Tineke Callant,Head Data Standards & Senior Biostatistical AnalystProcess Improvements
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OUTLINE
SDTM and ADaM: Standards review
A central Metadata Repository
ADaM implementation: Strategies
Conclusion
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CDISC: STANDARDS REVIEW
CDISC end-to-end !
•
CDASH identifies the (e)CRF data collection fields• SDTM defines a standard structure for study data tabulations
• ADaM specifies the fundamental principles for the creation ofanalysis datasets
CDASHspecs
eCRFdesign-tool
EDC -application
SDTM –define.xml –bookmarked
CRF
ADaM –define.xml
CDASH EDC - LibraryTrial data
acquisitionSubmission package
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STUDY DATA TABULATION MODEL (SDTM) &
ANALYSIS DATA MODEL (ADaM)
SDTM and ADaM: Hands-on solutions
•
Focus on submission standards: SDTM, ADaM, (define.xml)• Hands-on solutions for daily work:
– Manage a spectrum of SDTM implementations
– ADaM best build upon SDTM, not on ‘raw’ data
SDTM –define.xml
bookmarkedCRF
ADaM –define.xml
Data Tabulation Analysis
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SDTM & ADaM AT SGS
Data Management
•
SDTM datasets at (and before) database lockwith associated metadata
Statistics
• Statistical analysis on SDTM datasets
• ADaM datasets with associated metadata
SDTM –define.xml
bookmarked
CRF
ADaM –define.xml
DataManagement
Statistics
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STUDY DATA TABULATION MODEL (SDTM):
WHAT’S NEW, WHAT’S COMING?
Today
•
Implementation Guide v3.1.2, 12-NOV-2008• Amendment 1 to SDTM 1.2 (IG 3.1.2), 14-DEC-2011
• Alzheimer’s Disease v1.0, 30-NOV-2010
• + CRTDD v1.0.0, 09-FEB-2005
Coming up
• Non-Subject Data Supplement, draft 17-JUN-2011
• Device Supplement, draft 24-JAN-2012
• Virology draft domains, draft AUG-2011• Development program for 55 therapeutic area
standards in 5 years [CDISC strategic goals &themes]
SDTM –
define.xmlbookmarked
CRF
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FDA STUDY DATA STANDARDS CATALOG
Version 1.0; Effective 13-JUN-2011
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SDTM:THE CHALLENGE
SGS maintains 16 SDTM models!
• Multiple SDTM versions
• Multiple sponsors
– Custom controlled terminology
– Custom domains
– Custom variable implementations
• Multiple implementations per sponsor per SDTM version
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SDTM:THE CHALLENGE, AN EXAMPLE
SDS team TC: 15-Jul-2011
•
Holter data in Interventions domain
• Holter data in Findings domain
Example A) Mockups of Revised ProposalRow
STUDYID DOMAIN USUBJID PRSEQ PRTRT PROCCUR PRSTDTC PRENDTC
1 ABC123 PRABC123-
0011
HOLTERMONITOR
Y2011-01-01
T08:002011-01-02
T09:45
Ro
w
STUDYID DOMAIN USUBJID EGSEQ EGTESTCD EGTEST EGORRES EGORRESU EGDTC
1 ABC123 EGABC123-
0011 RR RR Interval 475 msecs
2011-01-01T08:10
2 ABC123 EGABC123-
0012 RR RR Interval 800 msecs
2011-01-01T10:08
Example B) Mockups of Original Proposal
Row
STUDYID DOMAIN USUBJID MPSEQ MPTESTCD MPTEST MPORRES MPSTAT MPDTC MPENDTC
1 ABC123 PRABC123-
0011 HOLTER
HolterMonitor
DONE2011-01-01
T08:002011-01-02
T09:45
Row
STUDYID DOMAIN USUBJID EGSEQ EGTESTCD EGTEST EGORRES EGORRESU EGDTC
1 ABC123 EGABC123-
0011 RR RR Interval 475 msecs
2011-01-01T08:10
2 ABC123 EGABC123-
001
2 RR RR Interval 800 msecs2011-01-01
T10:08
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SDTM AND ADaM INTERFACING: THE
CHALLENGE
SDTM concepts are standard, details are not
Due to:• Missing therapeutic area standards
• Missing controlled terminology items
• Flexible SDTM variables
– Permissible variables
– Flexible variable length» based on used codelist values (SDTM Amendment 1)
» only few variables lengths are fixed (e.g. --TESTCD, --TEST, --PARMCD, --PARM, QNAM, QLABEL, ARMCD)
to16 SDTMs 16 ADaMs ?
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SDTM SPECTRUM MANAGEMENT: THE
SOLUTION
Add a new dimension to your trials• Use Metadata from the start
Pull the CRF forms for all your
trials out of a metadata repository
into the (e)CRF design tool
Metadata Repository
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SDTM SPECTRUM MANAGEMENT: THE
SOLUTION
Add a new dimension to your trials
•
Use Metadata during the trial – Verify consistency of your trials
– Use the metadata repository to update the trial design in caseof protocol amendments
– Store the trial metadata in the metadata
repository for future reference
Metadata Repository
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SDTM SPECTRUM MANAGEMENT: THE
SOLUTION
Add a new dimension to your trials
•
Use Metadata till the end – Sponsor SDTM IGs with update option
copied from fixed SGS SDTM IGs
– Use the trial metadata in the metadatarepository to generate SDTM datasets
Metadata Repository
SDTM -define.xml
bookmarkedCRF
SGS: SDTM 1.1SGS: SDTM 1.2
XXX: SDTM 1.1 (v1)XXX: SDTM 1.1 (v2)XXX: SDTM 1.2 (v1)YYY: SDTM 1.2 (v1)YYY: SDTM 1.2 (v2)
2 14
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SDTM SPECTRUM MANAGEMENT:THE
SOLUTION
Add a new dimension to your trials
•
Share Metadata across standards and teams• ... and bring the SDTM spectrum closer to ADaM
Metadata Repository
StatisticsData Management
SDTM
SAS XPT datasetsdefine.xml
annotated CRF
ADaM
SAS XPT datasetsdefine.xml
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METADATA REPOSITORY: WHAT’S IN THE
BOX?
CDISC metadata
• SDTM version
• SDTM metadata• ...
Study characteristics
•
Therapeutic area• Clinical phase
• Trial design characteristics• ...
Project metadata• Study timelines
• Key Performance Indicators• ...
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OUTLINE – ADaM 2.1
Introduction
SDTM and ADaM implementation: Strategies
Linear method
Conclusion
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ADaM 2.1 – INTRODUCTION
Excel file → SAS datasets• codelist.sas7bdat
• domlist.sas7bdat• varlist.sas7bdat
Analysis Dataset Metadata – domlist.sas7bdat
Analysis Variable Metadata – varlist.sas7bdat
Dataset name Display format
Variable name Code list / Controlled terms – codelist.sas7bdatVariable label Source / Derivation
Variable type + Parameter identifier (Basic Data Structure (BDS))+ Length (SAS environment)+ Position in observation (SAS environment)
ADaM V2.1: Analysis Results Metadata (not required)
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ADaM 2.1 – INTRODUCTION
CDISC Analysis Data Model V2.1
• Fundamental principles
– Traceability
• Practical considerations
– Maintain the values and attributes of SDTM variables
CDISC ADaM implementation guide V1.0
• General variable naming convention
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Traceability
Flexible
Delivery of consistent analysis datasets
Easy to use (Excel file)
Easy to maintain (Excel file)
ADaM 2.1 – INTRODUCTION
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OUTLINE – ADaM 2.1
Introduction
SDTM and ADaM implementation: Strategies
Linear method
Conclusion
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STRATEGIES FOR IMPLEMENTING SDTM AND ADaM
STANDARDS: SUSAN KENNY – MICHAEL LITZSINGER
Parallel method
SDTM DomainsDBMS ExtractAnalysis Datasets
Retrospective method
DBMS Extract → Analysis Datasets → SDTM Domains
Linear method
DBMS Extract → SDTM Domains → Analysis Datasets
Hybrid method
DBMS Extract → SDTM Draft Domains → Analysis Datasets → SDTM Final Domains
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STRATEGIES FOR IMPLEMENTING SDTM AND ADaM
STANDARDS: SUSAN KENNY – MICHAEL LITZSINGER
Linear method
• Traceability
• CDISC SDTM/ADaM Pilot Project
• Recommended
DBMS Extract → SDTM Domains → Analysis Datasets
Hybrid method
• Traceability
• Amendment 1 SDTM V1.2 and SDTM IG V3.1.2
• Future?!?
DBMS Extract → SDTM Draft Domains → Analysis Datasets → SDTM Final Domains
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OUTLINE – ADaM 2.1
Introduction
SDTM and ADaM implementation: Strategies
Linear method
Conclusion
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LINEAR METHOD
Step 1
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LINEAR METHOD – STEP 1
CDISC SDTM IMPLEMENTATION GUIDE
...
...
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LINEAR METHOD – STEP 1
CDISC SDTM IMPLEMENTATION GUIDE
Any ADaM variable whose name is thesame as an SDTM variable must be acopy of the SDTM variable, and its label,
meaning, and values must not bemodified
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LINEAR METHOD – STEP 1
CHALLENGE: FLEXIBLE VARIABLE LENGTH
...
...
...
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LINEAR METHOD – STEP 1
CHALLENGE: FLEXIBLE VARIABLE LENGTH
CDISC SDTM IG• Version 5 SAS transport file format: max. 200 characters•
-- TESTCD and QNAM: max. 8 characters• -- TEST and QLABEL: max. 40 characters
Example: DM.RACE: $41, $50, and $200
Amendment 1 to SDTM V1.2 and SDTM IGV3.1.2•
Version 5 SAS transport file format: max. 200 characters! only if necessary !
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Traceability
Flexible Delivery of consistent analysis datasets
Easy to use
Easy to maintain
LINEAR METHOD – STEP 1
CHALLENGE: FLEXIBLE VARIABLE LENGTH
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LINEAR METHOD – STEP 1
SOLUTION: [SDTM] ↔ %ADAM(DS_ = )
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Example: LB.LBSCAT
LINEAR METHOD – STEP 1
CHALLENGE: PERMISSIBLE VARIABLES
Solution: [sdtm] ↔ %ADAM(ds_ = )
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LINEAR METHOD
Step 2
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LINEAR METHOD – STEP 2
SUPP--
QNAM → variable name
QLABEL → variable label
QVAL → variable type
→ variable length
e.g. SUPPDM SDTM dataset e.g. ADSL ADaM dataset
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LINEAR METHOD – STEP 2
SOLUTION: [SUPP] ↔ %ADAM(DS_ = )
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LINEAR METHOD
Step 3
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LINEAR METHOD – STEP 3
CHALLENGE: 16 SDTM → 16 ADAM?!?
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LINEAR METHOD – STEP 3
CHALLENGE: 16 SDTM → 16 ADAM?!?
1
4
2
7
5
6
8 9
11
3
10
1413
12
SDTM
16
15
ADaM
?
?
??
??
??
??
??
LINEAR METHOD STEP 3
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LINEAR METHOD – STEP 3SOLUTION: 1 CENTRAL MODEL + SPONSOR
SPECIFIC ADD-ONS
sponsor
specific
add-on
central
ADaMmodel
domlist.sas7bdat
varlist.sas7bdat
codelist.sas7bdat
domlist.sas7bdat
varlist.sas7bdat
codelist.sas7bdat
domlist.sas7bdat
varlist.sas7bdat
codelist.sas7bdat
1
1 Convert Excel file to SAS datasets (by ADaM administrator)
2
2 Combine central model and sponsor specific add-on (by study programmer)
1
LINEAR METHOD STEP 3
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Traceability
Flexible
Delivery of consistent analysis datasets
Easy to use
Easy to maintain
LINEAR METHOD – STEP 3SOLUTION: 1 CENTRAL MODEL + SPONSOR
SPECIFIC ADD-ONS
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LINEAR METHOD
Step 4
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LINEAR METHOD – STEP 4
CHALLENGE: SDTM MODEL NO. 1, 2, 3 ... ?
1
4
2
7
5
6
8 9
11
3
10
1413
12
SDTM
16
15
ADaM
?
?
??
??
??
??
??
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LINEAR METHOD – STEP 4
SOLUTION: CENTRAL METADATA REPOSITORY
CDISC metadata
• SDTM version
• SDTM metadata• ...
Study characteristics
• Therapeutic area
• Clinical phase
• Trial design characteristics• ...
Project metadata
• Study timelines
• Key Performance Indicators• ...
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LINEAR METHOD
Step 5
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LINEAR METHOD – STEP 5
CHALLENGE: FUTURE
SDTM
• Device Supplement, draft 24-JAN-2012
• Virology draft domains, draft AUG-2011
• Development program for 55 therapeutic area standards in 5years
ADaM
• BDS for Time-to-Event Analysis, draft 05-JAN-2011
• Data Structure for Adverse Event Analysis, draft 02-FEB-2011
Coming up
• ???
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OUTLINE – ADaM 2.1
Introduction
SDTM and ADaM implementation: Strategies Linear method
Conclusion
SDTM AND AD M HANDS ON SOLUTIONS
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Linear method:
• Recommended
• Challenging
Solution:
• SDTM: Central metadata repository• ADaM: Automatization, e.g. [sdtm], [supp] …
Study medata differences are handled efficiently
SDTM AND ADaM: HANDS-ON SOLUTIONS
CONCLUSION
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