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

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

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)

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

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 Consensus (Initial) Version Harmon- ized Version Testing Review Version Released (Production) Version 1.0 Comments addressed OK PSCC Review Ex Focused Review Public Review OK Comments to address by team Stage III: Education & Support Respond To Comments And Questions Educational Programs (EDU, OIS) Stage IV: Standards Update & Maintenance SPCC Review New Released (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 Review as needed Optional Ex Focused Review Note: Occasional bug fix releases may be issued as needed with team review only.

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

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.

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

CDASH Project Process Process (1) SDTM Variable Tables 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

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

CDASH Project Process Technical Leadership Committee (TLC) 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)

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

CDASH Process DM CO CM SU EX AE MH DS DV DA IE PE SC VS Process (4) SDTM Domains DM CO CM SU EX AE MH DS DV DA IE PE SC VS SDTM Basic CRF Elements 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 2) Add SDTM Variable Names 3) Add CT 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.

The AE, CM, DM and SC Streams have delivered 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.

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

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

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

Collaborative Group Review 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. ICV TLC Review Harmonized Version Collaborative Group Review Reviewed Version Public Review Released Version 1.0 AE Dec. 2006 March 2007 March – April 2007 April 2007 Q108 Q2 2008 CM Jan 2007 DM & SC Jan. 2007

Initial Consensus Version Collaborative Group Review CDASH Project Process 2nd set of domains Started in December 2006. Delivered ICVs end of February 2007. TLC review to start beginning of March. Initial Consensus Version TLC Review Harmonized Version Collaborative Group Review Reviewed Version Public Review Released Version 1.0 INC/EX February 2007 March – April 2007 April 2007 May – June 2007 June 2007 Q108 Q2 2008 MH & SU February 2007 PE & VS

Initial Consensus Version Collaborative Group Review CDASH Project Process Initial Consensus Version TLC Review Harmonized Version Collaborative Group Review Reviewed Version Public Review Released Version 1.0 Adverse Events December 2006 March 2007 March – April 2007 April 2007 Q108 Q2 2008 Prior & Concomitant Medication January 2007 Demographics & Subject Characteristics Inclusion/Exclusion Criteria February 2007 May – June 2007 June 2007 Medical History and Substance Use Physical Exam & Vital Signs End of Study/ Disposition May 2007 June – July 2007 July 2007 August – Sept. 2007 September 2007 Drug Accountability/ Exposure Protocol Deviations/ Comments Lab & ECG August 2007 September-October 2007 October 2007 November- December 2007 January 2008

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.

CDASH Project Status - March 2007

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.

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

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

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

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