CDISC Standards: Connecting Clinical Research and Healthcare

1. CDISC Standards: Connecting Clinical Research and Healthcare NCBO Meeting Signs, Symptoms and Findings 3 September 2008, Dallas TX Bron Kisler (CDISC) Gary Walker (Quintiles)

2. Strength through collaboration. CDISC operates to advance the continued improvement of public health by enabling efficiencies in medical research and related areas of healthcare. As a catalyst for productive collaboration, CDISC brings together individuals spanning the healthcare continuum to develop global, open, consensus-based medical research data standards.

3. * Specification referenced via FDA Final Guidance

4. Data Flow Using CDISC Standards = ODM - Operational Data Model (transport of data and metadata…”the message”) = SDTM - Study Data Tabulation Model and ADaM - Analysis Dataset Model (content) SEND for Non-clinical Data = Protocol Representation Standard (content) = Source data (other than SDTM/CRF data) = LAB – Laboratory Data Standard Integrated Reports Protocol Representation Patient Info Lab Data CDASH-eCRF Study Data (defined by SDTM) Study & Analysis Data Study & Analysis Data Trial Design Analysis Plan ODM XML ODM XML ODM XML Define.xml Reporting or Regulatory Submissions Warehouse (e)Source Document Operational & Analysis Databases Study Protocol

5. Interventions Events Findings Special Purpose Conmeds AE ECG Ques’aire Demog Exposure Disposition Incl/Excl SubjChar Comments SubjElements SubstUse MedHx Labs Vitals SubjVisits Deviations PhysExam DrugAcct SUPPQUAL Clinical Events PK Conc PK Param RELREC Micro MB Micro MS Trial Design (5 Tables) Submissions – SDTM version 3.1.2 SDTM = Study Data Tabulation Model

6. SDTM General Observation Classes Interventionsclass captures investigational, therapeutic and other treatments that are administered to the subject (with some actual or expected physiological effect) either as specified by the study protocol (e.g., “exposure”), coincident with the study assessment period (e.g., “concomitant medications”), or self-administered by the subject (such as alcohol, tobacco, or caffeine) Eventsclass captures planned protocol milestones such as randomization and study completion (“disposition”), and occurrences, conditions or incidents independent of planned study evaluations occurring during the trial (e.g., “adverse events”) or prior to the trial (e.g., “medical history”) Findingsclass captures the observations resulting from planned evaluations to address specific tests or questions such as laboratory tests, histopathology, ECG testing, and questions listed on questionnaires. Most findings are measurements, tests, assessments, or examinations performed on a subject in the clinical trial

7. CDISC Terminology Snapshot • Formalized CDISC Terminology Initiative in 2005 • Primary Objective: to define and support the terminology needs of the CDISC models across the clinical trial continuum (SDTM → CDASH) • Focus on “standard” terminology development and publication, beginning with SDTM ver3.1.1 • Key partnership with US National Cancer Institute Enterprise Vocabulary Services (NCI EVS) • External harmonization: ISO, HL7 RCRIM, FDA, HITSP, NCI, etc.

8. LOINC SNOMED MedDRA MeSH ICD’s . . . 60+ Controlled Vocabularies NCI Thesaurus CDISC Controlled Terminology

9. CDISC-led Project (initiated by ACRO) to address FDA Critical Path Initiative Opportunity #45 Mission: To develop a set of ‘content standards’ (element name, definition, metadata) for a core set of global data collection fields that will support clinical research studies. Scope: The initial scope is focused on the ‘safety data/domains’ common across all therapeutic areas Process: Begin with and map to SDTM version 3.1.1; focus on ‘CRF content’ not layout; collect CRF samples and id commonalities; work with Terminology Team on terminology proposals; follow CDISC consensus process Clinical Data Acquisition Standards Harmonization 9

10. CDASH Collaborative Group • 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 & Drug Administration (FDA) • NIH - NCI - caBIG • NIH - Clinical Research Policy Analysis & Coordination Program • National Clinical Research Resources (NCRR) • NIH - National Institute of Child Health & Human Development (NICHD) • National Library of Medicine (NLM) • Pharmaceutical Research and Manufacturers Association (PhRMA) • Society for Clinical Data Management (SCDM) 10

11. CDASH-ODM Connection

12. Creating CDASH-ODM Template CDASH Content ODM - Operational Data Model (Database Content and Structure) <ODM> <Study> <Meta … </Meta … </Study> </ODM> Terminology Codelists CDASH–ODM Template Presentation Extended ODM SDTM -Study Data Tabulation Model

13. ODM Building BlocksHow does CDASH Relate? Clinical Database Variable Name Controlled Terminology CDASH CRF Label/Question CDASH Core (Highly Recommended)

14. Optimal Solution from Standardized Content to any EDC System

15. Multi-Vendor Visualizations – PhaseForward

16. Multi-Vendor Visualizations - Medidata

17. CDISC ‘Healthcare Link’

18. = ODM (transport) = SDTM and Analysis Data (content) = Protocol information (content) = Source data (other than SDTM/CRF data) Data Flow Using CDISC Standardslinking clinical research & healthcare Electronic Health Record Patient Info HL7 and/or ODM XML HL7 and/or ODM XML Clinical Trial Data Integrated Reports Protocol Representation Patient Info Lab Data Study & Analysis Data CDASH-eCRF) Study Data (defined by SDTM) Study & Analysis Data Study Design Analysis Plan ODM XML ODM XML Define.xml ODM XML Operational & Analysis Databases Regulatory Submissions (e)Source Document Study Protocol 18

19. Workflow Integration: RFD EHR Clinical Research Sponsor Data Receiver Receives the data instance from the Form Filler. Forms Manager Serves up the form to the Form Filler. • Case Report Form (CRF) • CDASH • ODM Forms Filler Displays the form for completion in an EHR session Data Archiver Stores the electronic source document Primary Use RFD = Retrieve Form for Data Capture 19

20. RFD Proof of Concept 3. Form Manager pre-populates Lilly S001 form and returns to Form Filler who completes and submits the form 4. Data Receiver Receives and inserts data into Phase Forward’s Clintrial CDMS. Lilly/Quintiles Form Manager Data Receiver • CDASH data elements (demographics, AE, meds) hit 25/33 slots in Lilly CRF. • ODM + XForms allowed 4 EHRs to render the form on the first try! RFD 2. Form Filler forwards CDASH data elements to the Form Manager (to retrieve a pre-populated form) 5. Data Archiver stores the electronic source document. Form Filler Data Archiver Cerner Millennium 1. Site Investigator uses Cerner Millenium to retrieve an electronic case report form. 20

21. Other Healthcare Links

22. CDISC Standards & BRIDG Model(Biomedical Research Information Domain Group) Data Collection Submissions Glossary CDASH SDTM / SEND ODM ADaM Protocol LAB Analysis Data BRIDG is a mechanism for standards integration

23. BRIDG as a portal to Healthcare Data Collection CDASH Protocol Submissions B R I D G Glossary Healthcare SDTM / SEND B R I D G ODM ADaM HL7 RIM LAB Analysis Data

24. BRIDG Domain Analysis Model (implementation independent)

25. FDA IT Plan (CDISC-HL7 Message) Site Sponsor CDISC Content and Interchange Interchange: HL7 output file CDISC Content Trial Design CDASH Data Checker andLoader Sponsor Data Warehouse (ODM) FDA Reviewers SDTM ADaM Review Tools Janus FDA/NCI Analytical Data Warehouse Site Data Archive (ODM) MedWatch AE Reports (ICSR)