CDISC: Global Approach

2. CDISC: Global Approach To Accelerating Medical Research

3. CDISC Mission To develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare The CDISC Vision is informing patient care and safety through higher quality medical research. improve medical research

4. CDISC • Global, open, multi-disciplinary, vendor-neutral, non-profit standards developing organization (SDO) • Founded 1997, incorporated 2000 • Member-supported (>300 members, e.g. academia, biopharma, service / technology providers) • Liaison A Status with ISO TC 215 • Charter agreement with HL7 (2001) • Leadership of Joint Initiative Council (JIC) for Global Harmonization of Standards • Member of ANSI-led ISO TAG • Active Coordinating Committees (3C) • Europe, Japan, China, Korea • >> 90 countries in participant database

5. CDISC has established worldwide industry standards to support the electronic acquisition, exchange, submission and archiving of clinical research data and metadata to improve data quality and streamline medical and biopharmaceutical product development and research processes • Consensus-based development (COP-001) • Standards are freely available at www.cdisc.org • IP Policy ensures open standards

6. CDISC Organization • Volunteer participants and team members • CDISC Teams: Anyone can participate • 3Cs (CDISC Coordinating Committees) • User Networks (regional, often language-centered) • Technical Leadership Committee • Team leaders / co-leads • Oversees the standards development and project teams • Works to achieve operational and strategic goals

7. Information from healthcare (private, aggregated) to enable research Healthcare Research • Quality healthcare • Informed decisions • Personalized medicine • Patient safety and privacy • Public health • Improved therapies • Efficiencies/reduced costs • Discovery of new therapies • Understanding diseases • Testing/comparing therapies (CER) • Assessing efficacy • Monitoring safety • Understanding responses • (genomics, biomarkers) • Public health/quality evaluations • Post-marketing surveillance Inefficient cycle Research findings to inform healthcare decisions

8. Organization to Support CDISC TAC Gov FOC Board Strategy T L C Project Teams Board Committees: Education and Implementation Services Technical Projects Financial; Legal; HR PR/Communications Alliances User Networks CAB CCC Global Operations

9. CDISC Standards Development Process (COP-001) Stage I: Standard Definition/Team Initiation Need for Specific Standard(s) Identified (any stakeholder) Proposal to Board of Directors (via Operations) Review per strategy, budget priorities Team Leader ID And Team Formation (multidisciplinary) (Operations) 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 Public Review TLC Review External Focused Review Comments to address by team Stage III: Education & Support Respond To Comments And Questions Educational Programs (EDU, Operations) Stage IV: Standards Update & Maintenance TLC Review 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.

10. Joint Initiative Council Current leader: Bron Kisler, CDISC For the global harmonization of healthcare and related standards. BRIDG is going through the JIC Process; it is now an HL7 and CDISC standard – one ballot left in ISO (and CEN).

11. General Standards Organizations • ISO (cont.) • CDISC is a Liaison A status to ISO TC 215 (healthcare standards) • Possible because CDISC process conforms to ISO standards • Allows CDISC to skip some initial steps in ISO approval • Means CDISC standards can be approved as ISO standards • ANSI • American National Standards Institute, US representative to ISO • CDISC standards developed with HL-7 can be ANSI-accredited • CEN • European equivalent of ANSI

12. 2001 2000 2008 2002 2010 CDISC Around the Globe

13. Business Case For Using CDISC Standards

14. Gartner-PhRMA-CDISC Project • Business Case for using CDISC standards • Summary: • Using CDISC standards can save significant time and cost, especially when implemented in the early stages of the study • Opportunities for an additional impact on clinical research • Increased data quality • Data Integration / enhanced re-usability • Facilitates data exchange with partners • Enable software tools • Improve team communication • Facilitate regulatory reviews and audits Opportunity Value: Do More With Less

15. Value Implementation Tradeoffs: Greatest Value when Standards Implemented in Study Start-up 40% 40% 50% 80%

16. CDISC Standards and Data Flow

17. CDISC Standards • Glossary • SDTM - Study Data Tabulation Model • CDASH - Clinical Data Acquisition Standards Harmonization • ADaM - Analysis Data Model • LAB - Laboratory • Terminology • TDM - Trial Design Model • Protocol Representation

18. CDISC Standards • Therapeutic Area Standards • BRIDG - Biomedical Research Integrated Domain Group Model • SHARE – Shared Health and Clinical Research Electronic Library • ODM - Operational Data Model • RFD – Retrieve Form for Data Capture • define.XML • SEND - Standard for the Exchange of Non-clinical Data

19. www.cdisc.org CDISC Standards – Open and Free

20. Glossary

21. SME View Canonical View OWL View HL7 RIM View

22. CDISC is More than Standards! CDISC Vision Informing patient care and safety through higher quality medical research

23. Backup

24. CDISC Standards • SDTM - Study Data Tabulation Model • CDASH - Clinical Data Acquisition Standards Harmonization • ADaM - Analysis Data Model • LAB - Laboratory • Medical Devices • Terminology • TDM - Trial Design Model • Protocol Representation

25. CDISC Standards • Therapeutic Area Standards • BRIDG - Biomedical Research Integrated Domain Group Model • SHARE – Shared Health and Clinical Research Electronic Library • ODM - Operational Data Model • RFD – Retrieve Form for Data Capture • define.XML • SEND - Standard for the Exchange of Non-clinical Data

26. SDTM • Study Data Tabulation Model • Structure and content of clinical data in electronic regulatory submissions files • Managed by the SDS team (Submission Data Standards) • The model is in Version 1.2 • SDTM Implementation Guide (IG) is Version 3.1.2 • FDA now accepts Version 3.1.1 and 3.1.2 • Always check with reviewer before sending

27. SDTM IG • Provides information on • Variable and domain naming conventions • Dataset definitions for 21 subject data-related domains and several study description domains • How to create data relationships • How to develop new domains • How to think about and understand clinical data dataset structures

28. CDASH • Clinical Data Acquisition Standards Harmonization, Version 1.0 • ‘Content standards’ for a basic set of global industry-wide data collection fields to support clinical research • Not CRF layouts • System-independent, open source, free • Initial scope: 16 core safety domains • Covers both paper and electronic data capture

29. CDASH Content: Core Domains • Common Identifier Variables • Common Timing Variables • Adverse Events (AE) • Concomitant Medications (CM) • Comments (CO) • Drug Accountability (DA) • Demographics (DM) • Disposition (DS) • Protocol Deviations (DV) • ECG (EG) • Exposure (EX) • Inclusion Exclusion (IE) • Lab Test Results (LB) • Medical History (MH) • Physical Exam (PE) • Vital Signs (VS) • Subject Characteristics (SC) • Substance Use (SU)

30. CDASH Content • Data design best practices, e.g., • Use of yes/no questions • Date format • Recommended methodologies for creating data collection instruments • Common controlled terminology • Regulatory references for each domain

31. CDASH User Guide v1.0 • In development, expected publication 1Q10 • Will contain • General assumptions about each domain • Implementation examples • ODM XML structure for data transmission • Electronically-generated CRF examples • Variables not included in the standard • CDASH to SDTM mapping • Horizontal vs vertical data structures

32. ADaM • Analysis Data Model • Structure of analysis datasets for submission • Some limited information on specific fields expected • Planning to release a User Guide with more guidance on implementing the model

33. LAB • Provides specifications for electronic transfer of central lab data • Extensions for microbiology and ECG data • A subset of the most commonly used LOINC terms

34. Medical Devices • Currently in development • Will provide device-specific domains • Device properties • Device tracking • Device disposition • Device malfunctions • First stage addresses implantable devices and other similar devices • Later will include imaging and diagnostics

35. Terminology • Set of controlled terms used in CDISC standards • Provides the answers to the questions asked by the fields/variables • Maintained by NCI Electronic Vocabulary Services (EVS)

36. TDM • Trial/Study Design Model • Electronic representation of the schedule of activities (planned assessments, interventions, administrative activities, and encounters) • It’s the study schedule in searchable structured electronic format

37. Protocol • Defines trial elements electronically • Allows the protocol to be described electronically and the elements search and reused • Includes eligibility criteria, trial design elements (e.g., Arms, epochs), trial schedule of events, and selected fields required by regulatory authorities (e.g., date of first subject enrolled, sponsor name)

38. Therapeutic Area Standards • Draft standards are available for • Cardiovascular: Acute Coronary Syndrome • Pulmonary Tuberculosis • A draft standard is being produced for basic oncology tumor measurements

39. BRIDG • Biomedical Research Integrated Domain Group Model • Framework for linking and harmonizing the other standards • Defines each field as a concept with an agreed meaning and set of characteristics • Foundation for linking CDISC to EHR and other data sources

40. SHARE • Shared Health and Clinical Research Electronic Library • A standards authoring tool that • Facilitates gathering and comparing existing material to distill a preferred approach • Provides a repository for standard data elements • Permits some associations between elements • This is in development and has completed its first pilot

41. ODM • Operational Data Model • An XML definition for transmitting CDISC data between systems • Currently primarily on data exchange between labs and sponsors, and the like • Extension being developed to support data exchange for CDASH data, and data exchange of CDASH data with eHR applications

42. RFD • Retrieve Form for Data Capture • Broadly, it is “a method for gathering data within a user’s current application to meet the requirements of an external system.” (IHE Wiki) • “RFD supports the retrieval of forms from a form source, display and completion of a form, and return of instance data from the display application to the source application” (IHE Wiki) • CDISC: applied to the interface between eHR and Electronic Data Capture (EDC) systems • In development

43. define.XML • The metadata sent to the FDA describing the SDTM datasets in the regulatory submission • Based primarily on the first 5 columns of the SDTM IG • Written in XML

44. SEND • Standard for the Exchange of Non-clinical Data • SEND IG: An implementation of SDTM for animal toxicology data • Currently in Phase II pilot with the FDA

45. How It All Fits Together BRIDG Controlled Terminology SHARE Vendors ADaM CDASH Protocol Representation SDTM IG FDA Trial Design Model LAB Devices SEND ODM define.xml