SDTM AND ADaM: HANDS-ON SOLUTIONS - sgs.com

1 SDTM AND ADaM: HANDS-ON SOLUTIONSCDISC French Speaking User GroupParis, France17 February 2012 Joris De Bondt,Tineke Callant,Head data Standards & Senior Biostatistical Analyst Process Improvements2 OUTLINE SDTM and ADaM: Standards review A central Metadata Repository ADaM implementation: Strategies Conclusion3 CDISC: STANDARDS REVIEW CDISC end-to-end ! CDASH identifies the (e)CRF data collectionfields SDTM defines a standard structure for study data tabulations ADaM specifies the fundamental principles for the creation of analysisdatasets CDASH specseCRFdesign-toolEDC -applicationSDTM bookmarked CRFADaM EDC - LibraryTrial data acquisitionSubmission package4 study data tabulation model (SDTM) & ANALYSIS data model (ADaM) SDTM and ADaM: HANDS-ON SOLUTIONS Focus on submission standards: SDTM, ADaM, ( ) HANDS-ON SOLUTIONS for daily work: Manage a spectrumof SDTM implementations ADaM bestbuild upon SDTM, not on raw dataSDTM CRFADaM TabulationAnalysis5 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 metadataSDTM CRFADaM ManagementStatistics6 study data tabulation model (SDTM).

2 WHAT S NEW, WHAT S COMING? Today Implementation Guide , 12-NOV-2008 Amendment 1 to SDTM (IG ), 14-DEC-2011 Alzheimer s Disease , 30-NOV-2010 +CRTDD , 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 CRF7 FDA study data STANDARDS CATALOG Version ; Effective 13-JUN-20118 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 version9 SDTM:THE CHALLENGE, AN EXAMPLE SDS team TC: 15-Jul-2011 Holter data in Interventions domain Holter data in Findings domainExample A) Mockups of Revised Proposal Row STUDYID DOMAIN USUBJID PRSEQ PRTRT PROCCUR PRSTDTC PRENDTC 1 ABC123 PR ABC123-001 1 HOLTER MONITOR Y 2011-01-01 T08:00 2011-01-02 T09:45 Row STUDYID DOMAIN USUBJID EGSEQ EGTESTCD EGTEST EGORRES EGORRESU EGDTC 1 ABC123 EG ABC123-001 1 RR RR Interval 475 msecs 2011-01-01 T08:10 2 ABC123 EG ABC123-001 2 RR RR Interval 800 msecs 2011-01-01 T10:08 Example B) Mockups of Original Proposal Row STUDYID DOMAIN USUBJID MPSEQ MPTESTCD MPTEST MPORRES MPSTAT MPDTC MPENDTC 1 ABC123 PR ABC123-001 1 HOLTER Holter Monitor DONE 2011-01-01 T08:00 2011-01-02 T09.

3 45 Row STUDYID DOMAIN USUBJID EGSEQ EGTESTCD EGTEST EGORRES EGORRESU EGDTC 1 ABC123 EG ABC123-001 1 RR RR Interval 475 msecs 2011-01-01 T08:10 2 ABC123 EG ABC123-001 2 RR RR Interval 800 msecs 2011-01-01 T10:08 10 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 fewvariables lengths are fixed ( --TESTCD, --TEST, --PARMCD, --PARM, QNAM, QLABEL, ARMCD)to16 SDTMs16 ADaMs ?11 SDTM SPECTRUM MANAGEMENT: THE SOLUTION Add a new dimension to your trials Use Metadata from the startPull the CRF forms forallyourtrials out of a metadata repositoryinto the (e)CRF design toolMetadata Repository12 SDTM SPECTRUM MANAGEMENT: THE SOLUTION Add a new dimension to your trials Use Metadata during the trial Verify consistencyof your trials Use the metadata repository to updatethe trial design in case of protocol amendments Store the trial metadata in the metadata repository for future referenceMetadata Repository13 SDTM SPECTRUM MANAGEMENT: THE SOLUTION Add a new dimension to your trials Use Metadata till the end Sponsor SDTM IGs with update optioncopied from fixedSGS SDTM IGs Use the trial metadata in the metadata repository to generate SDTM datasetsMetadata RepositorySDTM bookmarked CRFSGS: SDTM SGS.

4 SDTM : SDTM (v1) XXX: SDTM (v2)XXX: SDTM (v1)YYY: SDTM (v1)YYY: SDTM (v2)21414 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 ADaMMetadata RepositoryStatisticsData ManagementSDTMSAS XPT annotated CRFADaMSAS XPT 15 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 ..16 OUTLINE ADaM Introduction SDTM and ADaM implementation: Strategies Linear method Conclusion17 ADaM INTRODUCTION Excel file SAS datasets Analysis Dataset Metadata Analysis Variable Metadata nameDisplay formatVariable nameCode list / Controlled terms labelSource / DerivationVariable type+ Parameter identifier (Basic data Structure (BDS))+ Length (SAS environment)+ Position in observation (SAS environment) ADaM.

5 Analysis Results Metadata (not required)18 ADaM INTRODUCTION CDISC Analysis data model Fundamental principles Traceability Practical considerations Maintain the values and attributes of SDTM variables CDISC ADaM implementation guide General variable naming convention19 ADaM INTRODUCTIONGENERAL VARIABLE NAMING CONVENTIONAny ADaM variable whose name is the same as an SDTM variable must be a copy of the SDTM variable, and its label, meaning, and values must not be modified20 Traceability Flexible Delivery of consistent analysis datasets Easy to use (Excel file) Easy to maintain (Excel file)ADaM INTRODUCTION21 OUTLINE ADaM Introduction SDTM and ADaM implementation: Strategies Linear method Conclusion22 STRATEGIES FOR IMPLEMENTING SDTM AND ADaM STANDARDS: SUSAN KENNY MICHAEL LITZSINGER Parallel methodSDTM DomainsDBMS ExtractAnalysis Datasets Retrospective methodDBMS Extract Analysis Datasets SDTM Domains Linear methodDBMS Extract SDTM Domains Analysis Datasets Hybrid methodDBMS Extract SDTM Draft Domains Analysis Datasets SDTM Final Domains23 STRATEGIES FOR IMPLEMENTING SDTM AND ADaM STANDARDS: SUSAN KENNY MICHAEL LITZSINGER Linear method Traceability CDISC SDTM/ADaM Pilot Project RecommendedDBMS Extract SDTM Domains Analysis Datasets Hybrid method Traceability Amendment 1 SDTM and SDTM IG Future?

6 !?DBMS Extract SDTM Draft Domains Analysis Datasets SDTM Final Domains24 OUTLINE ADaM Introduction SDTM and ADaM implementation: Strategies Linear method Conclusion25 LINEAR METHODStep 126 LINEAR METHOD STEP 1 CDISC SDTM IMPLEMENTATION METHOD STEP 1 CDISC SDTM IMPLEMENTATION GUIDEAny ADaM variable whose name is the same as an SDTM variable must be a copy of the SDTM variable, and its label, meaning, and values must not be modified28 LINEAR METHOD STEP 1 CHALLENGE: FLEXIBLE VARIABLE 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: : $41, $50, and $200 Amendment 1 to SDTM and SDTM Version 5 SAS transport file format: max. 200 characters! only if necessary !30 Traceability Flexible Delivery of consistent analysis datasets Easy to use Easy to maintainLINEAR METHOD STEP 1 CHALLENGE: FLEXIBLE VARIABLE LENGTH31 LINEAR METHOD STEP 1 SOLUTION: [SDTM] %ADAM(DS_ = )32 Example: METHOD STEP 1 CHALLENGE: PERMISSIBLE VARIABLESS olution: [sdtm] %ADAM(ds_ = )33 LINEAR METHODStep 234 LINEAR METHOD STEP 2 SUPP-- QNAM variable name QLABEL variable label QVAL variable type variable SUPPDM SDTM ADSL ADaM dataset35 LINEAR METHOD STEP 2 CHALLENGE: FLEXIBLE CODE LIST QLABEL is different for the same QNAM ExampleELIGCONF Subject Still EligibleELIGCONF Still Fulfill Eligibility Criteria QLABEL format ExampleRANDNO RANDOMIZATION NUMBERRANDNO Randomization Number QLABEL changes during the course of a study ExampleELIGIBLE SujectEligible For Dosing ELIGIBLE SubjectEligible For Dosing36 LINEAR METHOD STEP 2 SOLUTION.

7 [SUPP] %ADAM(DS_ = )37 LINEAR METHODStep 338 LINEAR METHOD STEP 3 CHALLENGE: 16 SDTM 16 ADAM?!?39 LINEAR METHOD STEP 3 CHALLENGE: 16 SDTM 16 ADAM?!?SDTM Column Resizing: Background and Industry Testing Results Warfield and Chhatre40 LINEAR METHOD STEP 3 CHALLENGE: 16 SDTM 16 ADAM?!?1427568911310141312 SDTM1615 ADaM????????????41 LINEAR METHOD STEP 3 SOLUTION: 1 CENTRAL model + SPONSOR SPECIFIC Excel file to SAS datasets (by ADaM administrator)22 Combine central model and sponsor specific add-on (by study programmer)142 Traceability Flexible Delivery of consistent analysis datasets Easy to use Easy to maintainLINEAR METHOD STEP 3 SOLUTION: 1 CENTRAL model + SPONSOR SPECIFIC ADD-ONS43 LINEAR METHODStep 444 LINEAR METHOD STEP 4 CHALLENGE: SDTM model NO. 1, 2, 3 .. ?1427568911310141312 SDTM1615 ADaM????????????45 LINEAR METHOD STEP 4 SOLUTION: CENTRAL METADATA REPOSITORY CDISC metadata SDTM version SDTM metadata.

8 study characteristics Therapeutic area Clinical phase Trial design characteristics .. Project metadata study timelines Key Performance Indicators ..46 LINEAR METHODStep 547 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 5 years ADaM BDS for Time-to-Event Analysis, draft 05-JAN-2011 data Structure for Adverse Event Analysis, draft 02-FEB-2011 Coming up ???48 OUTLINE ADaM Introduction SDTM and ADaM implementation: Strategies Linear method Conclusion49 Linear method: Recommended Challenging Solution: SDTM: Central metadata repository ADaM: Automatization, [sdtm], [supp] .. study medata differences are handled efficientlySDTM AND ADaM: HANDS-ON SOLUTIONSCONCLUSION50 CONTACTJ oris De BondtHead data Standards & Process Improvements -Clinical ResearchEmail: CallantSenior Biostatistical AnalystEmail.