© 2011

CDISC: Global Approach To Accelerating Medical Research

© 2011 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

© 2011 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

© 2011 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 IP Policy ensures open standards

© 2011 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

© 2011 Research findings to inform healthcare decisions Information from healthcare (private, aggregated) to enable research 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 Quality healthcare Informed decisions Personalized medicine Patient safety and privacy Public health Improved therapies Efficiencies/reduced costs Research Healthcare Inefficient cycle

© 2011 Organization to Support CDISC 8 Board CAB CCC Project Teams TLCTLC Gov FOC Strategy TAC User Networks Technical Projects Alliances Education and ImplementationServices PR/Communications Financial; Legal; HR Global Operations Board Committees:

© 2011 External Focused Review CDISC Standards Development Process (COP-001) 9 Need for Specific Standard(s) Identified (any stakeholder) Proposal to Board of Directors (via Operations) Working Plan (timelines, deliverables communication mech., resources req’d) (Team ) Consensus (Initial) Version Harmon- ized Version Team Leader ID And Team Formation (multidisciplinary) (Operations) Review per strategy, budget priorities Approve d Annual Review of Released Version (comments, chg reqsts, tests, plans) (Team) Released (Production) Version 1.0 Review Version Stage I: Standard Definition/Team Initiation Stage III: Education & Support Stage IV: Standards Update & Maintenance Stage II: Standards Development/Review/V 1.0 Release Working Plan (timelines, deliverables, communication mech., resources req’d) (Team) Consensus (Revised) Version Respond To Comments And Questions Educational Programs (EDU, Operations) Not Approved TLC Review Comments to address by team Public Review Comments addressed New Released (Production) Version Harmon- ized Version TLC Review Ex Focused Review Public Review as needed Optional Testing Note: Occasional bug fix releases may be issued as needed with team review only.

© 2011 Joint Initiative Council 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). Current leader: Bron Kisler, CDISC

© 2011 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

© 2011 CDISC Around the Globe

© 2011 Business Case For Using CDISC Standards

© 2011 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

© 2011 SubmissionAnalysis / Reporting Study ConductStudy Start-up I mplementation Tradeoffs: Greatest Value when Standards Implemented in Study Start-up 80%40%50% 40%

© 2011 CDISC Standards and Data Flow

© 2011 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

© 2011 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

© CDISC Standards – Open and Free

© 2011 Glossary 20

© 2011 SME View Canonical View HL7 RIM View OWL View

© 2011 CDISC is More than Standards! CDISC Vision Informing patient care and safety through higher quality medical research

© 2011 Backup

© 2011 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

© 2011 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

© 2011 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 FDA now accepts Version and Always check with reviewer before sending

© 2011 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

© 2011 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

© 2011 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) 29

© 2011 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 30

© 2011 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 31

© 2011 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

© 2011 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

© 2011 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

© 2011 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)

© 2011 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

© 2011 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)

© 2011 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

© 2011 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

© 2011 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

© 2011 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

© 2011 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

© 2011 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

© 2011 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

© 2011 How It All Fits Together 45 FDA Controlled Terminolog y BRIDG SEND CDASH ADaM SDTM IG define.xml LAB ODM Trial Design Model Devices Vendors SHARE Protocol Representatio n