© CDISC 2012 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 CDISC Standards Update

© CDISC 2012 Programme de la réunion du GUF CDISC du 17/12/2012

© CDISC 2012 Programme de la réunion du GUF CDISC du 17/12/2012

© CDISC 2012 Topics The State of our Standards The CDISC Technical Plan The CDISC Technical Roadmap CDISC SHARE CDISC, CFAST and Therapeutic Area Standards Development 4

© CDISC The CDISC Standards Guide

© CDISC Breaking News

© CDISC Click Standards Guides 7

© CDISC 2012 Key Technical Initiatives for 2012 Technical Strategy 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 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 8

© CDISC 2012 A New Process 9

© CDISC CDISC Technical Plan Oct. 2012

© CDISC 2012 Statistics DAM in BRIDG Tracking Statistical topics thru-out the study lifecycle. 11

© CDISC 2012 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 (eCRF or 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) 12

© CDISC 2012 CDISC Roadmap: A Work in Progress 13

© CDISC 2012 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. 14

© CDISC 2012 CDISC Technical Roadmap Foundational Standards Semantics Therapeutic Areas SDS Product Family CDASH Product Family SHARE BRIDG Track 1 Track 2 Track 3 SEND PROTOCOL Others XML Technologies Glossary ADAM Controlled Terminology Health Care Interoperability IHE ONC/Euro-rec CRProcess/SHARE Transport Layer XML, OWL, JSON… Semantic Layer BRIDG/SHARE Functional Layer SDTM, SEND, ADaM, CDASH Implementation Layer Therapeutic Area Guides, Healthcare Interoperability Kits SDTM v4 15

© CDISC 2012 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. CDISC SHARE VISION 16

© CDISC 2012 Variations in the Concept of “Bleeding” Source: Establishing and Maintaining Therapeutic Area Data Standards Draft White Paper 17

© CDISC 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 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

© CDISC 2012 SME View Canonical View HL7 RIM View OWL View

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

© CDISC 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 Graphics adapted from Source by Sue Dubman, Sanofi-Aventis 21 bridg

© CDISC 2012 SHARE Top-Level Functions 22 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 Notifications to users re object changes Manage listserv Manage SHARE MDR Framework Components Monitor User Activity Maintain Metrics Manage System Availability

© CDISC 2012 CDISC SHARE Library Contents 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. 23

© CDISC BRIDG ISO data types Integrated BRIDG / ISO Templates Research Concepts Operational Collections 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) 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. Integrated BRIDG / ISO Templates use BRIDG classes and relationships to fashion small re-usable patterns that are commonly needed in clinical research 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 Template. BRIDG is the foundation model for SHARE that provides classes, attributes and associations use to creates core building blocks. SHARE MDR Framework Other External Resources (e.g. value Sets)

© CDISC 2012 Relationship SHARE - Describes the Links between the Metadata Diagram – Dave Iberson-Hurst

© CDISC 2012 The CDISC SHARE MODEL SDTM Variables CDASH Variables Controlled Terminology BRIDG Classes Data types CDISC SHARE MODEL 26

© CDISC 2012 Content Mapping

© CDISC 2012 SHARE Concept-Based View 28 C ONTROLLED T ERMINOLOGY D EFINITIONS C ONTROLLED T ERMINOLOGY D EFINITIONS SHARE FOUNDATION Define. XML Define. XML TFLs/SDTM Analysis/ADa M CRFs/CDASH Protocol/TDM VIEWS BRIDG D ATA T YPES BRIDG D ATA T YPES S HARE C ONCEPTS ( E. G. BLOOD PRESSURE ) S HARE C ONCEPTS ( E. G. BLOOD PRESSURE )

© CDISC 2012 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 Q 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

© CDISC 2012 Controlled Terminology CDISC Alliances / Partners / Collaborations 30

© CDISC 2012 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. Launch of

© CDISC 2012 C-Path, A Public-Private Partnership with the FDA: Why ? The number of new drugs approved per billion USD spent on 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 32

© CDISC 2012 What’s Wrong with the Process?? Throughout the drug development enterprise : o Data to demonstrate efficacy & safety are defined and collected differently o Measurements of efficacy and safety are based on differing criteria o Methodologies for design of clinical trials for new drugs differ widely Standards are needed 33

© CDISC 2012 C-Path: What DEVELOP INTERNATIONAL STANDARDS Measurement standards o Molecular biomarkers for efficacy and patient classification o Molecular biomarkers for toxicity o Imaging biomarkers for efficacy and patient classification o Patient-, observer-, clinician- reported outcomes Methods standards o Disease models and clinical trial simulation tools o In vitro models ACQUIRE REGULATORY QUALIFICATION Recognition, approval for a given context of use 34

© CDISC 2012 C-Path: How  Act as trusted neutral third party  Convene industry, academia, and government for pre-competitive collaboration  6 Global consortia  41 Companies, scientists  The best science  Shared risk and costs  Iteratively involve FDA in the development process  Regulatory participation, guidance  Official recognition of standards through “qualification” 35

© CDISC 2012 C-Path: Who We’ve Convened 36 Partners

© CDISC 2012 C-Path: What We Do DEVELOP INTERNATIONAL STANDARDS Data standards o CDISC clinical data standards for therapeutic areas o 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 37

© CDISC

© CDISC 2012 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 Therapeutic Area Standards Content 39

© CDISC 2012 C CFAST TA Standards Governance Model CFAST Program Manager(s) CFAST Steering Committee TA Project Core Teams Project Manager Terminology Lead Clinical LeadBRIDG Modeler Data Standards LeadData Analyst Statistics ConsultantTechnical Writer CDISC Foundational Standards Teams CDISC Leadership Community and Process CFAST Support: IT Admin Communications 40 CFAST Scientific Advisory Comm. FDA CDISC C-Path TransCelerate BioPharma

© CDISC 2012 A New Process 41

© CDISC

© CDISC

© CDISC 2012 Strength through collaboration. 44