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 Controlled Terminology represents one of CDISC’s broadest and most ambitious initiatives. We formalized… Primary Objective…across the clinical trial continuum from the point of data collection through to eSubmissions

CDISC Mission Clinical Data Interchange Standards Consortium ...to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare Controlled Terminology represents one of CDISC’s broadest and most ambitious initiatives. We formalized… Primary Objective…across the clinical trial continuum from the point of data collection through to eSubmissions

CDISC Standards Description 2004* 2001* 2005* 2002 2004 Fall 2008 Implementation Version Release Date SDTM, SEND (Reg. Submission) 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 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

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

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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, HL7 RCRIM, etc. Controlled Terminology represents one of CDISC’s broadest and most ambitious initiatives. We formalized… Primary Objective…across the clinical trial continuum from the point of data collection through to eSubmissions

Guiding Principles Adopt…Adapt…Develop Philosophy Evaluate and/or utilize existing terminology 1st 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 When we first kicked-off the CDISC Terminology Initiative we identified a set a key working principals (or key objectives) to help guide terminology development. I am pleased to say these guiding principals still hold true today. The first objective is to “define and support…” The initial scope of work here centered around defining terminology for the SDTM. … Since we are a standards org, we need to be sure we are consistent and standardized throughout the org and across all the various CDISC teams…The CDISC Technical Roadmap Finally, we want to “Ensure a harmonized approach…” (NCI, FDA, SDOs) Harmonization is a recurring theme that you will be hearing, because it is a critically important component of standards development. It is the harmonization aspect that will ultimately determine the interoperability and usability of the standards we develop. Standards development in isolation does not work… In looking for a Terminology partner there was only one organization that met these important criteria.

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 The Enterprise Vocabulary Services of the National Cancer Institute has committed dedicated resources and is making a significant investment in the CDISC Terminology Program. This is of tremendous value to CDISC, as it allows us to leverage EVS’s rich knowledge / expertise in the area of Terminology Development and Production as well as their mature terminology infrastructure. Also important to CDISC, is the fact that NCI EVS is supporting key FDA Vocabulary projects in the same manner. This ensures well-aligned synergistic goals that effectively triangulate the partnership(s).

Proposed Rule (key driver) Federal Register / Volume 71, No. 237 / Monday, December 11, 2006 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.

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 MedDRA MeSH ICD’s . 60+ Controlled Vocabularies NCI Thesaurus

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

POSITION codelist Example (SDTM & CDASH – VSPOS, EGPOS / HL7) Standard Terminology Codelist Sitting Prone Standing Supine Fowlers Semi-Fowlers Trendelenburg Reverse Trendelenburg Right Lateral Decubitus Left Lateral Decubitus CDISC Controlled Terminology If each of the 3 companies shared a standardized code list, information can be exchange more seamlessly and semantic interoperability would be possible. To eliminate any potential confusion, it is important to note that there is actual controlled terminology for both the field name (or code list name) and each permissible value. **This is a highly debated codelist

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-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 First the SDTM was evaluated, and we identified specific fields (or variables) that needed Controlled Terminology. Then, project teams were formed around specific terminology sets. A terminology project team is responsible for a terminology set from initial development and through to its production. These terminology project teams are made up of SDS Team Members and representatives from Pharma/CROs, Academia and Government Agencies and Institutions. We ensure each project team has international representation. 1 – Our 1st project (SDTM Package-1) is now IN PRODUCTION. This basically includes SDTM fields with easier and more well-defined code lists distributed broadly across the SDTM. This project was our training wheels to learn what the development of true Controlled Terminology really meant. One of our lessons learned is it was too broad in scope. 2 – For our 2nd project, we applied a very focused approach developing terminology for a single field (Labtest). This development work has proceeded rapidly. 3 & 4 – Applying the lessons learned from these 1st two projects, we have settled on an approach somewhere in between – SDTM Package 2A and 2B

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 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) First the SDTM was evaluated, and we identified specific fields (or variables) that needed Controlled Terminology. Then, project teams were formed around specific terminology sets. A terminology project team is responsible for a terminology set from initial development and through to its production. These terminology project teams are made up of SDS Team Members and representatives from Pharma/CROs, Academia and Government Agencies and Institutions. We ensure each project team has international representation. 1 – Our 1st project (SDTM Package-1) is now IN PRODUCTION. This basically includes SDTM fields with easier and more well-defined code lists distributed broadly across the SDTM. This project was our training wheels to learn what the development of true Controlled Terminology really meant. One of our lessons learned is it was too broad in scope. 2 – For our 2nd project, we applied a very focused approach developing terminology for a single field (Labtest). This development work has proceeded rapidly. 3 & 4 – Applying the lessons learned from these 1st two projects, we have settled on an approach somewhere in between – SDTM Package 2A and 2B

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) First the SDTM was evaluated, and we identified specific fields (or variables) that needed Controlled Terminology. Then, project teams were formed around specific terminology sets. A terminology project team is responsible for a terminology set from initial development and through to its production. These terminology project teams are made up of SDS Team Members and representatives from Pharma/CROs, Academia and Government Agencies and Institutions. We ensure each project team has international representation. 1 – Our 1st project (SDTM Package-1) is now IN PRODUCTION. This basically includes SDTM fields with easier and more well-defined code lists distributed broadly across the SDTM. This project was our training wheels to learn what the development of true Controlled Terminology really meant. One of our lessons learned is it was too broad in scope. 2 – For our 2nd project, we applied a very focused approach developing terminology for a single field (Labtest). This development work has proceeded rapidly. 3 & 4 – Applying the lessons learned from these 1st two projects, we have settled on an approach somewhere in between – SDTM Package 2A and 2B

Future Plans (Cont.) 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) First the SDTM was evaluated, and we identified specific fields (or variables) that needed Controlled Terminology. Then, project teams were formed around specific terminology sets. A terminology project team is responsible for a terminology set from initial development and through to its production. These terminology project teams are made up of SDS Team Members and representatives from Pharma/CROs, Academia and Government Agencies and Institutions. We ensure each project team has international representation. 1 – Our 1st project (SDTM Package-1) is now IN PRODUCTION. This basically includes SDTM fields with easier and more well-defined code lists distributed broadly across the SDTM. This project was our training wheels to learn what the development of true Controlled Terminology really meant. One of our lessons learned is it was too broad in scope. 2 – For our 2nd project, we applied a very focused approach developing terminology for a single field (Labtest). This development work has proceeded rapidly. 3 & 4 – Applying the lessons learned from these 1st two projects, we have settled on an approach somewhere in between – SDTM Package 2A and 2B

Strength through collaboration… 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… First the SDTM was evaluated, and we identified specific fields (or variables) that needed Controlled Terminology. Then, project teams were formed around specific terminology sets. A terminology project team is responsible for a terminology set from initial development and through to its production. These terminology project teams are made up of SDS Team Members and representatives from Pharma/CROs, Academia and Government Agencies and Institutions. We ensure each project team has international representation. 1 – Our 1st project (SDTM Package-1) is now IN PRODUCTION. This basically includes SDTM fields with easier and more well-defined code lists distributed broadly across the SDTM. This project was our training wheels to learn what the development of true Controlled Terminology really meant. One of our lessons learned is it was too broad in scope. 2 – For our 2nd project, we applied a very focused approach developing terminology for a single field (Labtest). This development work has proceeded rapidly. 3 & 4 – Applying the lessons learned from these 1st two projects, we have settled on an approach somewhere in between – SDTM Package 2A and 2B As a catalyst for productive collaboration, CDISC brings together individuals spanning the healthcare continuum to develop global, open, consensus-based medical research data standards.