CDISC Standards Update

1. CDISC Standards Update Pierre-Yves Lastic Sanofi R&D, Chair-Elect, CDISC Board of Directors Réunion du Groupe des Utilisateurs Francophones des standards CDISC, Chilly-Mazarin, 17 December 2012

2. Programme de la réunion du GUF CDISC du 17/12/2012

3. Programme de la réunion du GUF CDISC du 17/12/2012

4. Topics • The State of our Standards • The CDISC Technical Plan • The CDISC Technical Roadmap • CDISC SHARE • CDISC, CFAST and Therapeutic Area Standards Development

5. The CDISC Standards Guide

6. Breaking News

7. 1-Click Standards Guides

8. Key Technical Initiatives for 2012 Technical Strategy Technical Projects Increase transparency Improve processes Annual Planning Standards Review Council New Process Definition Coordinated new versions of foundational standards New provisional state Kickoff CFAST Appreciate our volunteers • Communicate updated CDISC vision and roadmap • Incorporate BRIDG in standards development • Begin transition to SHARE • Improve use of online collaboration tools for standards development • Increase involvement by global volunteers

9. A New Process

10. CDISC Technical Plan Oct. 2012

11. Statistics DAM in BRIDGTracking Statistical topics thru-out the study lifecycle.

12. CDISC’s Healthcare Link Vision A set of profiles and standards to automate the clinical trial process flow of EHR-enabled platforms from patient recruitment thru clinical trial data capture: Clinical research protocol: • Retrieve Process for Execution (RPE) • Clinical Research Process Content (CRPC) • Proposed Research Matching • CDISC SDM-XML • Clinical research documents (eCRFor adverse event reports) to be pre-populated by existing clinical data in EHRs: • Retrieve Form for Data Capture (RFD) • Clinical Research Document (CRD) • Drug Safety Content (DSC) • Redaction Service Profile (RSP) • Proposed Data Element Exchange and Patient Authored Note • CDISC CDASH and ODM for data exchange and archive • Confidentiality and security aspects • Consistent Time (CT) • Cross-Enterprise User Assertion (XUA) • Audit Trail Node Authentication (ATNA)

13. CDISC Roadmap: A Work in Progress

14. Building Blocks of the CDISC Roadmap • Programs - A related collection of products or product areas: • Foundational Standards (SDTM, CDASH, ODM, ADaM, etc.) • Semantics (BRIDG, SHARE) • Therapeutic Areas • Healthcare Link • Teams – responsible for a foundational product family or product • SDS, CDASH, ADaM, XML Tech, etc. • Sub-teams are assigned to specific projects or product areas by a standing team (Devices) • Projects – Finite sets of activities involving members from 1 or more teams to deliver a specific product or deliverable • Product deliverables: (Implementation Guides, schemas, models other documents) • Device IG, Virology IG, CDASH SAE, SDTM in XML, etc. • A foundation based on BRIDG and SHARE.

15. CDISC Technical Roadmap Foundational Standards Transport Layer XML, OWL, JSON… SDTM v4 SDS Product Family CDASH Product Family SEND Semantic Layer BRIDG/SHARE PROTOCOL ADAM XML Technologies Functional Layer SDTM, SEND, ADaM, CDASH Others Semantics Implementation Layer Therapeutic Area Guides, Healthcare Interoperability Kits SHARE BRIDG Glossary Controlled Terminology Therapeutic Areas Track 1 Track 2 Track 3 Health Care Interoperability IHE ONC/Euro-rec CRProcess/SHARE

16. CDISC SHARE VISION 16 A global, accessible electronic metadata library, which through advanced technology, enables precise and standardized data element definitions and richer metadata that can be used in applications and studies to improve biomedical research and its link with healthcare. http://www.cdisc.org/cdisc-share

17. Variations in the Concept of “Bleeding” Source: Establishing and Maintaining Therapeutic Area Data Standards Draft White Paper

18. BRIDG – Part of the SHARE Foundation BRIDG Purpose:A collaborative effort to produce a shared view of the dynamic and static semantics that collectively define a shared domain-of-interest. The semantic foundation for HL7/CDISC-based application and message development Domain-of-interest/scope: Protocol-driven research A Unified Modeling Language (UML) Model of the data (using ISO 21090 datatypes), organization, resources, rules, and processes involved in the formal assessment of the utility, impact, or other pharmacological, physiological, or psychological effects of a drug, procedure, process, or device on a human, animal, or other biologic subject or substance plus all associated regulatory artifacts required for or derived from this effort. Stakeholders: Governance Process:Board of Directors prioritizes projects and committee consults with projects and harmonizes project models into main model with help of project analysts/SMEs 18

19. SME View Canonical View OWL View HL7 RIM View

20. BRIDG Model Content (Layer 2) Documents Study Subjects Studies Study Design People and their Roles Study Activities, Observations and Results Adverse Events Organizations and their Roles Regulatory Specimens Products and Study Agents Specimen Collection 20

21. Single, trusted, authoritative source for CDISC data standards Concepts, metadata, collections, relationships, value sets across the full spectrum of CDISC content Links research to healthcare concepts to support interoperability Aligned with NCI Semantic Systems bridg Graphics adapted from Source by Sue Dubman, Sanofi-Aventis 21 21

22. SHARE Top-Level Functions • Manage User Roles • Manage User Profiles • Manage Password • Manage User Dashboard • Manage Work Items • Manage Standard Objects • Manage Audit Trail • Search and Browse • Import • Export • Print • Send Notificationsto users re object changes • Manage listserv • Manage SHARE MDR Framework Components • Monitor User Activity • Maintain Metrics • Manage System Availability 22

23. CDISC SHARE Library Contents 23 • Metadata (including BRIDG, SDTM and CDASH) • Trial Design Metadata • Definitions • Datatypes (ISO 21090) • Links to controlled terminology (CT) dictionaries via the NCIt (which links to CDISC CT, SNOMED, ICD9, ICD10, UMLS, etc.) • Implementation instructions • Links to analysis concepts.

24. SHARE MDR Framework Other External Resources (e.g. value Sets) Versioned Standards A Versioned Standard is comprised of a set of Operational Collections and associated variables and rules for a specific use case (e.g., SDTM, CDASH) Operational Collections An Operational Collection is a grouping of Research Concepts. There may be additional rules between objects within the Operational Collection. An Operational Collection may be analogous with a SDTM Domain, a CRF, an ADaM data set, or a similar level of operational structure. Research Concepts Basic elements that are the foundation for the content described in the SHARE repository. A Research Concept defines one or more related pieces of clinical data, which is developed using an Integrated BRIDG / ISO 21090 Template. Integrated BRIDG / ISO 21090 Templates Integrated BRIDG / ISO 21090 Templates use BRIDG classes and relationships to fashion small re-usable patterns that are commonly needed in clinical research BRIDG ISO 21090 data types BRIDG is the foundation model for SHARE that provides classes, attributes and associations use to creates core building blocks. 24

25. SHARE - Describes the Links between the Metadata Relationship Relationship Relationship Diagram – Dave Iberson-Hurst

26. The CDISC SHARE MODEL CDISC SHARE MODEL BRIDG Classes 21090 Data types SDTM Variables CDASH Variables Controlled Terminology 26

27. Content Mapping

28. SHARE Concept-Based View VIEWS Share Concepts (e.g. blood pressure) Controlled Terminology Definitions BRIDG 21090 Data Types Protocol/TDM CRFs/CDASH Analysis/ADaM TFLs/SDTM SHARE FOUNDATION Define. XML 28

29. SHARE Status Update • RFI issued in August – 24 responses; 10 short-listed • Software vendors, academics, system integrators • Draft RFP due to be released in December - targeting a decision by Q1 2013 • Updated business requirements will soon be posted on CDISC website • Currently exploring additional partnership and funding options. • Goal is to have a release 1 prototype environment in initial use by end of 2013. 29

30. CDISC Alliances / Partners / Collaborations Controlled Terminology 30

31. Launch of Coalition For Accelerating Standards and Therapies CFAST is an initiative of CDISC and the Critical Path Institute to accelerate clinical research and medical product development by facilitating the creation and maintenance of data standards, tools, and methods for conducting research in therapeutic areas important to public health.

32. C-Path, A Public-Private Partnership with the FDA: Why ? 32 • The number of new drugs approved per billion USD spenton R&D has halved every 9 years since 1950 • Costs have grown steadily • Requires >$1B and ±15 years to bring a new drug to market • “The average drug developed by a major pharmaceutical company costs at least $4 billion, and it can be as much as $11 billion.” The Truly Staggering Cost of Inventing New Drugs. Forbes 2/20/12 • Process improvement is needed • Solutions require collaborative approaches that include both the public and the private sector

33. What’s Wrong with the Process?? 33 • Throughout the drug development enterprise: • Data to demonstrate efficacy & safety are defined and collected differently • Measurements of efficacy and safety are based on differing criteria • Methodologies for design of clinical trials for new drugs differ widely • Standards are needed

34. C-Path: What 34 • DEVELOP INTERNATIONAL STANDARDS • Measurementstandards • Molecular biomarkers for efficacy and patient classification • Molecular biomarkers for toxicity • Imaging biomarkers for efficacy and patient classification • Patient-, observer-, clinician- reported outcomes • Methodsstandards • Disease models and clinical trial simulation tools • In vitro models • ACQUIRE REGULATORY QUALIFICATION • Recognition, approval for a given context of use

35. C-Path: How 35 • Act as trusted neutral third party • Convene industry, academia, and government for pre-competitive collaboration • 6 Global consortia • 41 Companies, 1000+ scientists • The best science • Shared risk and costs • Iteratively involve FDA in the development process • Regulatory participation, guidance • Official recognition of standards through “qualification”

36. C-Path:Who We’ve Convened Partners 36

37. C-Path: What We Do 37 DEVELOP INTERNATIONAL STANDARDS • Datastandards • CDISC clinical data standards for therapeutic areas • Alzheimer’s disease, tuberculosis, others • MEET REGULATORY NEEDS • 58 disease areas in 5 years • FDA deadline for required data submission using CDISC standards in 2017 • EXPANSION OF DATA STANDARDS MISSION THROUGH CFAST

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39. Therapeutic Area Standards Content Baseline Content for Initial Release • Essential core data elements with definitions, data types (simple and ISO 21090), BRIDG and SDTM mappings • Mindmap/model of Disease Area concepts • Standard CDASH CRFs with SDTM annotations • User/Implementation Guide with permissions statement • Minimum value sets (code lists) with definitions • SDTM domains and examples Potential Additional Content • Domain Analysis Model • Representative ADaM Models • Added content (concepts, domains, terms, CDASH) • Sample SDM-XML study designs • Examples of SEND non-clinical data

40. CFAST TA Standards Governance Model CFAST Steering Committee CFAST Scientific Advisory Comm. CDISC Leadership C FDA CFAST Program Manager(s) CDISC Foundational Standards Teams TA Project Core Teams Project Manager Terminology Lead Clinical Lead BRIDG Modeler Data Standards Lead Data Analyst Statistics Consultant Technical Writer CDISC C-Path • CFAST Support: • IT • Admin • Communications TransCelerate BioPharma Community and Process

41. A New Process

44. Strength through collaboration. 44