CDASH Initiative

1. CDASH Initiative CDASH Project Description & Status Rhonda Facile Project Leader, CDISC

2. CDASH Project Process • Outline • Background and Charter • CDISC COP 001 • Project Organization • Project Process • SDTM • Review of Progress • Next Steps • Activities & Project Notes • Accomplishments to Date • Future • Core Team Contact

3. CDASH Project Process • C-path opportunity #45 • Continues ACRO’s CRF Standardization Initiative Project Charter • To develop a set of ‘content standards’ (element name, definition, metadata) for a basic set of global data collection fields that will support clinical research studies. The initial scope will be the ‘safety data domains’ to support clinical trials. • These safety domains cut across all therapeutic areas, beginning with 12-14 domains. CDISC COP (COP-001) • Follow the CDISC COP Standards Process (COP-001)

4. CDISC Standards Development Process (COP-001) Primary Stages Stage I: Standard Definition/Approval Multidisciplinary Team Initiation; Working Plan Development Stage II: Standards Development-Consensus Model; Reviews by External Focused Group and Open Public; Harmonization and Testing throughout; V1.0 Release Stage III: Education & Support Stage IV: Standards Update & Maintenance

5. Standards Development Process for CDISC (COP-001) Current Status Stage I: Standard Definition/Team Initiation Need for Specific Standard(s) Identified (any stakeholder) Proposal to Board of Directors (via OIS) Review per strategy, budget priorities Team Leader ID And Team Formation (multidisciplinary) (OIS) Working Plan (timelines, deliverables communication mech., resources req’d) (Team ) Approved Not Approved Stage II: Standards Development/Review/V 1.0 Release Testing Consensus (Initial) Version Harmon- ized Version Review Version Released (Production) Version 1.0 Comments addressed OK Public Review PSCC Review Ex Focused Review OK Comments to address by team Stage III: Education & Support Respond To Comments And Questions Educational Programs (EDU, OIS) SPCC Review Stage IV: Standards Update & Maintenance NewReleased (Production) Version Annual Review of Released Version (comments, chg reqsts, tests, plans)(Team) Working Plan(timelines, deliverables,communication mech.,resources req’d)(Team) Consensus(Revised)Version Harmon-ized Version Public Reviewasneeded Optional Ex Focused Review Note: Occasional bug fix releases may be issued as needed with team review only.

6. Achieving Global Consensus Project Organization Collaborative Group CDISC TAC Core Team (n=9) Stream Members

7. Achieving Global Consensus Project Organization • Streams must ensure input from all relevant functions: • Statisticians • Data Managers • Clinical Study Coordinators • Clinical Research Associates • Investigators • Clinical Program Managers • Both US and EX-US • Volunteers affiliated with global organizations are asked to include ex-US input into their stream’s standards development process. Need more representation from these functions Need more ex-US Representation.

8. Achieving Global Consensus Participants in the CDASH Initiative Other = Academic Research Organizations (1), Government (NIH, NCI (2)), Hospitals (2), Universities (14), Military (1)

9. CDASH Project Process Process (1) • Start with SDTM Data Variable Tables Use mandatory SDTM variables as a basis for the CDASH review process. • Refer to ACRO CRF Samples when available • Focus on CRF Content, not CRF Layout SDTM Variable Tables

10. CDASH Project Process Process (2) • Collect CRF samples • Evaluate commonalities/differences of CRF samples and SDTM • Document data points included/excluded with justifications • Guiding principles: variables should – • Start with the current SDTM Implementation guide & tables • Make sure all SDTM required elements are included either directly or indirectly • Be “standard” but flexible to allow customization within defined limits • Limit variables to required and necessary • Comply with regulatory requirements • Reduce redundancies; Not duplicate information found elsewhere in CRFs • Increase collection of meaningful data • Facilitate use of standards by all users • Be appropriate for use both pre and post approval studies • Allow consistent and efficient data collection/storage/transmission and analysis

11. CDASH Project Process Process Deliverables (3) • Reach agreement on BASIC (mandatory) CRF Data Elements • Map to SDTM using SDTM variable names (leveraged from the SDS Team) • Add Controlled Terminology (leveraged from the Terminology Team) • Add definitions • Write completion guidelines/instructions • Proceed to the next step in the Consensus Process as specified in COP-001 Technical Leadership Committee (TLC)

12. Achieving Global Consensus Detailed Consensus process Stage II: Standards Development/Review/V 1.0 Release Per Domain Testing Consensus (Initial) Version Harmon- ized Version Review Version Released (Production) Version 1.0 Comments addressed OK Public Review TLC Review Collaborative Group Review OK Comments to address by team ~1 week ~3 months ~1 month ~1 month ~1 month ~1 month ~1 month Entire process takes ~ 8 months

13. 3) Add CT 2) Add SDTM Variable Names Process (4) SDTM Domains SDTM Basic CRF Elements DM CO CM SU EX AE MH DS DV DA IE PE SC VS CDASH Process Subsets Vetted by “Front End” Stakeholders (Streams comprised of Invs, CRAs, Data Managers, Statisticians, etc.) DM CO CM SU EX AE MH DS DV DA IE PE SC VS Subset of 1)Basic Data Collection Elements from SDTM Domains 1) ”Basic Data Collection (CRF) Elements” = data elements that cut across all therapeutic areas and apply to most clinical trials. Leveraged from work done by the SDS team, collection of CRFs samples etc. 2) SDTM Variable Names; leveraged from work done by the SDS team. 3) CT = Controlled Terminology; leveraged from the work done by the Terminology Team.

14. CDASH Project Process • Progress The AE, CM, DM and SC Streams have delivered their Initial Consensus Versions (ICV). The following slides show the basic (mandatory) CRF data collection elements identified by the streams. Note: Conditional and optional data elements were also identified and included in the ICVs, however the initial remit is to focus on the basic data elements.

15. AE – Basic Data Collection Elements SDTM Data Variables AESEQ AEGRPID AERIFID AESPID AETERM AEMODIFY AEDECODE AECAT AESCAT AEOCCUR AEBODSYS AELOC AESEV AESER AEACN AEACNOTH AEREL AERELNST CDASH *Basic Data Collection (CRF) Elements AEPTT AEOUT AESCAN AESCONG AESDISAB AESDTH AESHOSP AESLIFE AESOD AESMIE AECONTRT AETOXGR AESTDTC AEENDTC AESTDY AEENDY AEDUR AEENRF AETERM AESTDTC AEENDTC AESER AESDTH AESHOSP AESLIFE AESOD AESMIE AESEV AETOXGR AEREL AEACN AEOUT (n=14) (n=36) *Basic = Mandatory

16. CM – Basic Data Collection Elements SDTM Data Variables CMSEQ CMGRPID CMSPID CMTRT CMODIFY CMDECODE CMCAT CMSCAT CMOCCUR CMSTAT CMREASND CMINDC CMCLAS CMCLASCD CMDOSE CMDOSTXT CMDOSU CDASH *Basic Data Collection (CRF) Elements CMDOSFRM CMDOSFRQ CMDOSTOT CMDOSRGM CMROUTE CMSTDTC CMENDTC CMSTDY CMENDY CMDUR CMSTRF CMENRF CMTRT CMSTDTC CMSTRF CMENDTC CMENRF (n=5) (n=29) *Basic = Mandatory

17. DM & SC – Basic Data Collection Elements SDTM Data Variables BRTHDTC AGE AGEU SEX RACE ETHNIC ARMCD ARM COUNTRY DMDTC DMDY CDASH *Basic Data Collection (CRF) Elements • BRTHDTC • Year of Birth • Month of Birth • SEX • RACE (n=3) (n=11) *Basic = Mandatory

18. CDASH Project Process 1st set of domains • Started work during the Project Kick-off meeting, 18 October 2006 at SAS Institute, Cary, NC. • Deliverables to complete TLC review by ~middle of March. • Collaborative Group review to start ~end of March/beginning of April.

19. CDASH Project Process 2nd set of domains • Started in December 2006. • Delivered ICVs end of February 2007. • TLC review to start beginning of March.

20. CDASH Project Process

21. CDASH Project Process • The 3rd set of domains (DA& EX, CM & DV, End of Study/DS) will be initiated at the beginning of March. • 4th set of domains (Lab & ECG) to start beginning of June.

22. CDASH Project Status - March 2007

23. Achieving Global Consensus CDASH Activities & Project Notes • Webinar - Held 22 January. • Press Release – soon! • Teleconferencing – continues q2 weeks • Core Team contacts – frequent, TCs q 2 weeks. • CDASH web portal - up and used. To expand access to new streams. • CDISC web site – a valuable source of info. Will facilitate public review phase of project.

24. Achieving Global Consensus Accomplishments to Date: • Successful Kick-off meeting (October 2006) • List of over 260 volunteers (varying degrees of participation) • Initiation of 1st set of domains • Delivery of ICVs for 1st set of domains • Initiation of 2nd set of domains • CDASH web portal – up • Successful CDASH Webinar held (333 Attendees – 53 International) • Delivery of ICVs for 2nd set of domains • Initiation of 3rd set of domains

25. CDASH Project Process Future? • Standardize layout • Standardize edit language • Standardize basic therapeutic area standards? • Support CDISC Forum/Help Desk • New Domains to be “CDASHed” • Update of CDASH developed domains • SLs and Stream Members to support TLC in future reviews of new standards

26. Achieving Global Consensus CDASH Core Team Contact Information • Rhonda Facile rfacile@cdisc.org • Gary Walker gary.walker@quintiles.com • Dorothy Dorotheo DDorotheo@intermune.com • David E. Tatum TATUM_DAVID_E@LILLY.COM • Paul Bukowiec Paul.Bukowiec@mpi.com • Trisha Simpson Trisha.Simpson@schwarzbiosciences.com • Shannon Labout shannon.labout@charter.net • Liz Nulton-Bodiford liz.m.nulton-bodiford@gsk.com • Jay Leeka Jay.Leeka@astrazeneca.com • Alec Vardy Alec.Vardy@cvt.com

27. Achieving Global Consensus Thanks to all the CDASH project volunteers for their time and commitment to the CDASH Project.