1. CDISC Controlled Terminology HITSP Harm. Subcommittee 1 October 2008 Bron Kisler (CDISC) bkisler@cdisc.org

2. CDISC Snapshot Global standards organization initiated in 1997 as a volunteer group; incorporated as non-profit in 2000 Established worldwide standards to support the electronic acquisition, exchange and submission of clinical research data 200+ corporate sponsors and member organizations (Global Pharmas, Service Organizations, Technology Vendors, Academic Institutions) Established Coordinating Committees and annual events in North America, Europe and Japan Expanding activities in China and India ISO Liaison A organization

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

4. CDISC StandardsDescription Implementation Version Release Date SDTM, SEND (Reg. Submission) Ready for regulatory submission of CRT Over 10,000 downloads as of late-2007 2004* ODMCDISC Transport Standard for data interchange (acquisition, exchange, documentation and archive) 2001* Define.xmlCase Report Tabulation Data Definition Specification (submission documentation) 2005* LABContent standard – available for transfer of clinical lab data to sponsors 2002 ADaM (Analysis Data) Analysis data for submissions - general considerations document and examples 2004 Protocol Representation Collaborative effort to develop machine- readable standard protocol with data layer Fall 2008 Terminology Codelists Developing standard terminology to support all CDISC standards 2006-07 Pkg-1 2007-08 Pkg-2 CDASH (Data Collection) Data acquisition (CRF) standards Sept. 2008 * Specification referenced via FDA Final Guidance

5. Submissions Data Collection SDTM / SEND Glossary ODM LAB CDASH Protocol CDISC Standards ADaM Analysis Data

7. Terminology Overview

8. Terminology Snapshot Primary Objective: to define and support the terminology needs of CDISC standards across the clinical trial continuum (SDTM → CDASH) Focus on “standard” terminology codelist development and publication, beginning with SDTM IG version 3.1.1 (safety data domains) Key partnership with US National Cancer Institute Enterprise Vocabulary Services (NCI EVS) with terms coded in NCI Thesaurus Key harmonization activities with FDA, ISO, NCI, HL7 RCRIM, etc.

9. Guiding Principles Adopt…Adapt…Develop Philosophy Evaluate and/or utilize existing terminology 1 st Expand existing vocabularies where incomplete, working with vocabulary developer / owner Harmonize across CDISC standards and with other pre-existing vocabulary initiatives Address international needs for global projects and organizations Ensure a sustainable “open source” environment and infrastructure for production terminology supporting terminology evolution

10. Dedicated terminology experts and resources CDISC controlled terminology development, harmonization, publication and maintenance Established terminology infrastructure and standard operating procedures CDISC work space in NCI Thesaurus where terms are coded NCI EVS Partnership

11. The Food and Drug Administration is proposing to amend the regulations governing the format in which clinical study data and bioequivalence data are required to be submitted for new drug applications (NDAs), biological license applications (BLAs), and abbreviated new drug applications (ANDAs). The proposal would revise our regulations to require that data submitted for NDAs, BLAs, and ANDAs, and their supplements and amendments be provided in an electronic format that FDA can process, review, and archive. The proposal would also require the use of standardized data structure, terminology, and code sets contained in current FDA guidance (the Study Data Tabulation Model (SDTM) developed by the Clinical Data Interchange Standards Consortium) to allow for more efficient and comprehensive data review. Federal Register / Volume 71, No. 237 / Monday, December 11, 2006 Proposed Rule (key driver)

12. FDA PDUFA IV IT Plan …excerpt “For terminology standards, the FDA partners with the National Cancer Institute Enterprise Vocabulary Services (EVS). The NCI EVS hosts the FDA terminologies and makes them freely available to the public.” NCI EVS supports FDA vocabulary initiatives – Structured Product Label (SPL) – Regulated Product Submission (RPS) – Individual Case Safety Report (ICSR)

13. CDISC-FDA Harmonization NCI Thesaurus LOINC SNOMED MedDRA MeSH ICD’s. 60+ Controlled Vocabularies http://www.cancer.gov/cancertopics/terminologyresources/

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

15. Sitting Prone Standing Supine Fowlers Semi-Fowlers Trendelenburg Reverse Trendelenburg Right Lateral Decubitus Left Lateral Decubitus CDISC Controlled Terminology CDISC Controlled Terminology POSITION codelist Example (SDTM & CDASH – VSPOS, EGPOS / HL7) Standard Terminology Codelist

16. Terminology – Production & Development

17. http://www.cdisc.org/standards/terminology/index.html http://www.cancer.gov/cancertopics/terminologyresources/CDISC SDTM Package 1: 30 codelists & 825 controlled terms distributed broadly across SDTM Labtest Package 1: single codelist with 180 controlled terms for Laboratory Test Results (commonly used for Analytes) SDTM Package-2A: 12 codelists & 590 controlled terms for ECG, Con Meds, Drug Exposure and Substance Use, including Units & Frequency SDTM Package-2B: 7 codelists & 330 controlled terms for Location (LOC), Disposition Event, Race, Subject Chars, Marital Status, Skin Classification and Skin Type Labtest Package 2: Additional 260 controlled terms for Laboratory Test Results SDTM Terminology (~2300 production terms)

18. See What’s New on CDISC homepage http://www.cdisc.org/ http://www.cdisc.org/ SDTM Package-3: – 6 code lists & 70 controlled terms developed – Available for public review through Oct. 17 and will be moved into production by year’s end – Drug Accountability Test (DATEST), Evaluator, Reference Range Indicator, Relationship Type, Specimen Type, Specimen Condition Labtest Package-3: – SDTM – 180 additional terms developed and available for public review through Oct. 17 – Terms aligned between SDTM and SEND – Ongoing consideration to align with LOINC CDASH-Specific Codelists: – Ongoing/Resolved (MHONG) and Prompt for Substance Use (SUNCF) SDTM & CDASH Terminology (~220 terms available for public review)

19. What’s Next?

20. Complete terminology for SDTM IG version 3.1.1 (December 2008) Formalize terminology maintenance process via NCI EVS mechanism to address additions and change requests Complete terminology alignment for CDASH version 1.0 (early Spring 2009) Consider new SDTM domains (Pharmacokinetics, Microbiology) Future Plans

21. Support and harmonize terminology with other maturing CDISC standards (ADaM, SEND) Continue extending harmonization with other standards initiatives (ISO, HL7, CEN, HITSP) Align terminology with BRIDG model and to support CDISC-HL7 message project(s) Continue to support disease-specific standards activities (TB, CV) Future Plans (Cont.)

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