1. CDASH Initiative Rhonda Facile Project Director, CDISC CDASH Project Update Atlantic User Group 21 February 2008

2. 2 CDISC Snapshot Global, open, multi-disciplinary non-profit organization –Founded in 1997; incorporated in 2000 –Nearly 200 member organizations Biopharmaceutical companies Academic Research Institutes Technology Vendors, etc… –Active Coordinating Committees Europe Japan –Additional activities Australia India S. America and Africa Established industry standards to support the electronic acquisition, exchange, submission and archiving of data to support regulated clinical research –Freely available on the CDISC website (www.cdisc.org)www.cdisc.org –Developed through open, consensus-based approach

3. 3 Agenda History Charter Collaborative Group Key Collaborations COP-001 Project Organization Work Stream Procedures Current Status Focus 2008 Core Team Contact Thanks!

4. 4 History Critical Path Initiative #45; Build on work started by ACRO Jan 2006 - CDISC requested to take leadership role as established standards development organization during the DIA Open Forum “Creating Clinical Trial Efficiencies Through Standard Data Collection”. June 2006 – Initial Collaborative Group (10) announced by Dr. Woodcock at Annual DIA Meeting in Philadelphia “Human Subject Protection/Bioresearch Monitoring Initiative and Critical Path Update” October 2006 – Collaborative Project Kickoff, Cary N.C.

5. 5 Charter To develop a set of ‘content standards’ (element name, definition, metadata) for a basic set of global industry- wide data collection fields that support clinical research. The initial scope - ‘safety data/domains’. These safety domains cut across all therapeutic areas. Follow CDISC Operating Procedure for Standards Development (COP-001).

6. 6 Collaborative Group - Role provides expertise and strategic input to the CDASH Project Team. contributes and/or helps identify resources as needed to enable achievement of the mission, goals and deliverables.

7. 7 Collaborative Group Members American Medical Informatics Association (AMIA) Association of Clinical Research Organizations (ACRO) Association of Clinical Research Professionals (ACRP) Baylor College of Medicine Biotechnology Industry Organization (BIO) Clinical Data Interchange Standards Consortium (CDISC) Clinical Research Forum Critical Path Institute Duke Clinical Research Institute (DCRI) Food and Drug Administration (FDA) National Institutes of Health (NIH) –NCI-EVS –NCI-caBIG –Clinical Research Policy Analysis & Coordination Program –National Clinical Research Resources (NCRR) –National Institute of Child Health & Human Development (NICHD) Pharmaceutical Research and Manufacturers Association (PhRMA) Society for Clinical Data Management (SCDM)

8. 8 Key Collaborations NIH –NCI-EVS –NCI-caBIG –Clinical Research Policy Analysis & Coordination Program –National Clinical Research Resources (NCRR) –National Institute of Child Health & Human Development (NICHD) CDISC SDS Team CDISC Terminology Team Healthcare Link

9. 9 CDASH – SDS Team FDA - Proposed Rule require (not just accept) electronic submissions require submissions to be in the SDTM format proposed 2 year implementation (proposed rule not yet written) Federal Register / Volume 71, No. 237 / Monday, December 11, 2006 So…CDASH collection variables must map into the SDTM.

10. 10 CDASH - Terminology CDASH: aligning SDTM terminology projects with CDASH requirements…full harmonization planned for Q1 2008 CDASH = Questions Terminology = Answers

11. 11 CDASH - IHE Integrating the Healthcare Enterprise (IHE) Electronic Health Records (EHR) Using CDASH Data Collection Variables to creating a profile, that can be used to populate a basic eCRF. Facilitate Single Source data entry.

12. 12 CDISC Standards Development Process (COP-001) Primary Stages Stage I: Standard Definition/Approval Multidisciplinary Team Initiation; Working Plan Development Stage III: Education & Support Stage IV: Standards Update & Maintenance Stage II: Standards Development-Consensus Model; Reviews by External Focused Group and Open Public; Harmonization and Testing throughout; V1.0 Release

13. 13 Organization Stream Members Core Team CDISC Technical Advisory Committee CDASH Collaborative Group 11 CDASH Streams (sub-groups) ~190 volunteers CDISC Technical Leadership Committee

14. 14 Organization Stream membership: Statisticians Medical Monitors/Clinical Scientists Regulatory Affairs Drug Safety Data Managers Clinical Study Coordinators Clinical Research Associates Investigators Clinical Program Managers Statistical Programmers Database programmers Need more multi-national input! Participants in the CDASH Initiative Other = Academic Research Organizations, Government (NIH, NCI), Hospitals, Universities, Military.

15. 15 Process Start with Study Data Tabulated Model (SDTM) Initial Focus on CRF Content, not CRF Layout Refer to ACRO CRF Samples (where available) Collect CRF samples Evaluate commonalities/differences of CRF samples Document data points included/excluded with justifications

16. 16 Deliverables Agree on basic data collection fields Map to SDTM Terminology - proposals Terminology Team Write definitions and completion instructions for clinical site and Sponsors Proceed to the next step in the Consensus Process

17. 17 Status Package-1: Adverse Events (AE) Concomitant Medication (CM) Demographics (DM) Subject Characteristics (SC) Started October 2006 TLC and Collaborative Group (CG) reviews - completed CG comments are now being addressed and a “Reviewed Version” achieved Consensus (Initial) Version Harmon- ized Version Released (Production) Version 1.0 Review Version TLC Review OK Collaborative Group Review OKOK Public Review

18. 18 Status Package-2: Inclusion/Exclusion Criteria (IE) Medical History (MH) Substance Use (SU) Physical Exam (PE) Vital Signs (VS) Started December 2006 TLC and Collaborative Group (CG) reviews are completed CG comments being addressed, “Reviewed Version” created OK Consensus (Initial) Version Harmon- ized Version Released (Production) Version 1.0 Review Version TLC Review Collaborative Group Review OKOK Public Review

19. 19 Status Package-3: Drug Accountability (DA) Exposure (EX) Comments (CO) Deviations (DV) Disposition (DS) Started March 2007 TLC and Collaborative Group review complete CG comments being addressed and a “Reviewed Version” created OK Consensus (Initial) Version Harmon- ized Version Released (Production) Version 1.0 Review Version TLC Review Collaborative Group Review OKOK Public Review

20. 20 Status Package-4: Lab (LB) ECG (EG) Started July 2007 TLC review completed CG review ongoing – comments due 22 Feb. Consensus (Initial) Version Harmon- ized Version Released (Production) Version 1.0 Review Version TLC Review Collaborative Group Review OKOK Public Review

21. 21 Status – February 2008

22. 22 CDASH Deliverable – per domain

23. 23 Focus – 2008 Demo – Using CDASH Variables 1. CDASH Standard Forms 2. CDISC SDTM Standard 3. CDASH Forms + SDTM Standard = Annotated Form 5. Standard electronic metadata configures collection system 4. Annotated Form + ODM Standard = Standard electronic metadata (XML) <Meta… </Meta…

24. 24 Focus 2008 & Onward CDISC Supported Activities Refine and post CDASH final draft for public review Refine and post CDASH V. 1.0 on CDISC.org. Development & implement CDASH training program. Present the CDASH standards at conferences, webinars and user group meetings. Collect feedback from “Early Implementers” and update CDASH v. 1.0 as required (follow Stage IV of COP-001) “CDASH” New Domains as they emerge. Future Activities? Standardize basic therapeutic area data variables (cooperate with other ongoing initiatives) Devices, Imaging…perhaps

25. 25 CDASH Project Process CDASH Core Team Contact Information Rhonda Facilerfacile@cdisc.orgrfacile@cdisc.org Gary Walkergary.walker@quintiles.comgary.walker@quintiles.com Dorothy DorotheoDDorotheo@intermune.com David E. Tatumtatum4@comcast.net Paul BukowiecPaul.Bukowiec@mpi.comPaul.Bukowiec@mpi.com Trisha SimpsonTrisha.Simpson@UCB-roup.comTrisha.Simpson@UCB-roup.com Shannon Laboutslabout@csscomp.com Liz Nulton-Bodifordliz.m.nulton-bodiford@gsk.com Jay LeekaJay.Leeka@astrazeneca.com Alec Vardya.vardy@comcast.net Kim TruettKim.Truett@kctdm.comKim.Truett@kctdm.com Holly PetersonHolly.Peterson@frx.com Kit Howardkit@kestrelconsultants.com

26. 26 We have come along way….. but there is much left to be done Thanks to all the volunteers who have worked to get us where we are today! Please Review the CDASH Draft when posted in early April 2008! Visit cdisc.org often to keep informed or contact rfacile@cdisc.org.

27. 27 Strength through collaboration.