CDISC Controlled Terminology HITSP Harm Subcommittee 1 October

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

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

CDISC Mission . . . to develop and support global, platformindependent data standards that enable information system interoperability to improve medical research and related areas of healthcare

CDISC Standards Description Implementation Version Release Date SDTM, SEND Ready for regulatory submission of CRT Over 10, 000 downloads as of late-2007 2004* ODM CDISC Transport Standard for data interchange (acquisition, exchange, documentation and archive) 2001* Define. xml Case Report Tabulation Data Definition Specification (submission documentation) 2005* LAB Content standard – available for transfer of 2002 clinical lab data to sponsors ADa. M 2004 (Analysis Data) Analysis data for submissions - general considerations document and examples Protocol Representation Collaborative effort to develop machinereadable 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 acquisition (CRF) standards Sept. 2008 (Reg. Submission) (Data Collection) * Specification referenced via FDA Final Guidance

CDISC Standards Submissions Data Collection Glossary SDTM / SEND ODM CDASH ADa. M LAB Analysis Data Protocol

Terminology Overview

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, HL 7 RCRIM, etc.

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

NCI EVS Partnership • 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

Proposed Rule (key driver) 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

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)

CDISC-FDA Harmonization http: //www. cancer. gov/cancertopics/terminologyresources/ LOINC SNOMED Med. DRA Me. SH ICD’s NCI Thesaurus . . . 60+ Controlled Vocabularies

Submissions – SDTM version 3. 1. 2 Interventions Events Conmeds AE ECG Ques’aire Exposure Disposition Incl/Excl Subj. Char Subst. Use Med. Hx Labs Vitals Findings Special Purpose Demog Comments RELREC SUPPQUAL Deviations Phys. Exam Drug. Acct Clinical Events PK Conc PK Param Subj. Visits Micro MB Micro MS Trial Design (5 Tables) SDTM = Study Data Tabulation Model Subj. Elements

POSITION codelist Example (SDTM & CDASH – VSPOS, EGPOS / HL 7) Standard Terminology Codelist CDISC Controlled Terminology • • • Sitting Prone Standing Supine Fowlers Semi-Fowlers Trendelenburg Reverse Trendelenburg Right Lateral Decubitus Left Lateral Decubitus

Terminology – Production & Development

SDTM Terminology (~2300 production terms) • 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-2 A: 12 codelists & 590 controlled terms for ECG, Con Meds, Drug Exposure and Substance Use, including Units & Frequency • SDTM Package-2 B: 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 & CDASH Terminology (~220 terms available for public review) • See What’s New on CDISC homepage 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 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)

What’s Next?

Future Plans • 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 (Cont. ) • Support and harmonize terminology with other maturing CDISC standards (ADa. M, SEND) • Continue extending harmonization with other standards initiatives (ISO, HL 7, CEN, HITSP) • Align terminology with BRIDG model and to support CDISC-HL 7 message project(s) • Continue to support disease-specific standards activities (TB, CV)

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