CDISC Controlled Terminology across the Clinical Trial Continuum Bay Area Implementation Network 6 March 2008 Bron Kisler Co-Founder / Director of Terminology
CDISC Terminology Initiative Overview / Background Terminology Development / Harmonization Production Spreadsheet TB & Cardiology Projects
Terminology Program Snapshot Formalized CDISC Terminology Program in 2005, initially focusing on SDTM terminology requirements Primary Objective: to develop and align terminology across all CDISC standards, spanning the clinical trial continuum (SDTM CDASH) Terminology Team comprised of 60+ team members (Global Pharmas, Regulators, Academia, CROs, etc.) with work distributed across 4 project teams Key partnership with US National Cancer Institute Enterprise Vocabulary Services (NCI EVS) Combined CDISC Terminology & HL7 RCRIM Vocabulary teams to ensure common development
Working Principles Evaluate and/or utilize existing terminology 1 st Expand existing vocabularies where incomplete, working with vocabulary developer / owner Harmonize across CDISC Models and with preexisting 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 CDISC work space in NCI Thesaurus with supporting infrastructure NCI EVS supports FDA vocabulary initiatives SPL, ICSR and RPS
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.
SDTM 3.1.1 Domains Interventions Findings Events Exposure Labs InclExcl AE Adverse Events ConMeds Vitals SubjChar Disp. Subst Use PhysExam ECG MedHist QS **50+ SDTM fields identified as candidates for controlled terminology codelists
AE Relatedness field - AEREL AE Relatedness to Study Drug? (No standard Codelist defined) Company 1 No Unlikely Possible Probably Definite Company 2 Not Related Doubtful Possible Probable Very Likely Company 3 NO YES / Unknown
AE Relatedness field - AEREL AE Relatedness to Study Drug? (Standard Terminology Codelist aka Value Set ) CDISC Controlled Terminology Standard Codelist No Unlikely Possible Probably Definite
AE Relatedness field - AEREL AE Relatedness to Study Drug? (Standard Terminology across CDISC Standards) CDASH No Unlikely Possible Probably Definite SDTM No Unlikely Possible Probably Definite SEND No Unlikely Possible Probably Definite
Terminology Development & Harmonization
SDTM Terminology (production ~1600 terms) SDTM Package 1: 31 codelists & 825 controlled terms distributed broadly across SDTM Labtest Package 1: 2 codelists with 180 controlled terms for Analytes SDTM Package-2A: 7 code lists & 590 controlled terms for ECG, Con Meds, Drug Exposure and Substance Use, including Units & Frequency http://www.cancer.gov/cancertopics/terminologyresources/ New Activities: assess production representation and usability; change requests & governance; maintenance & versioning (aligned with MedDRA)
SDTM Terminology (development ~650 terms) SDTM Package-2B: 12 code lists & 350 controlled terms developed and available for public review (AE, PE, VS and Subject Chars) Includes terminology set for anatomical location (SDTM LOC fields); both NCI Thesaurus and SNOMED were considered to be wellrepresentative of needs Labtest Package 2/3: SDTM: 200+ additional terms developed and available for public review (Labtest Package 2) SDTM/SEND: 100 terms in development for Vitamins, Enzymes, Immunology, Common drugs from drug screen (Labtest Package 3) Ongoing discussions with LOINC New SDTM projects to be launched in March per terminology gap analysis (SDTMIG 3.1.1, CDASH)
Internal Harmonization CDISC Glossary: to be represented in EVS NCI Thesaurus environment with SDTM terminology CDASH: aligning SDTM terminology with CDASH requirements; harmonization timeline pending SDTM-CDASH gap analysis SEND: initial gap analysis with SDTM complete; joint development activities underway BRIDG (HL7 RCRIM): high level analysis complete and harmonization plans in discussion
US Federal Harmonization NCI Thesaurus ICD s LOINC SNOMED MedDRA MeSH... 60+ Controlled Vocabularies
External Harmonization (semantic links to healthcare) ISO: Global harmonization via ISO TC215 WG6 per proposal from ICH; participating standards organizations ISO, ICH, CEN, HL7 & CDISC LAB: discussing solution to link SDTM Labtest values with LOINC codes TB & Cardiology: CDISC and HL7 style artifacts released for public review Other: Imaging, Microbiology, PGx, Medical Devices
2008 Terminology Priorities 1. Finalize terminology needed for SDTM IG Ver 3.1.1 2. Support / harmonize with other priority CDISC projects CDASH, SEND, Glossary, BRIDG 3. Support projects via HL7 RCRIM BRIDG, FDA Projects, CDISC-HL7 Message 4. Change control, governance and versioning 5. Develop integrated implementation plan to align terminology with other CDISC standards 6. New SDTM 3.1.2 domains and semantic links with healthcare
Production Spreadsheet
Tuberculosis (TB) & Cardiology (CV) Projects
Sponsored by the US National Institutes of Health Primary Aim: Improve interoperability by standardizing CV & TB data elements NIH ROADMAP FOR MEDICAL RESEARCH RE-ENGINEERING THE CLINICAL RESEARCH ENTERPRISE ( CV & TB grants awarded to Duke University in 2005 )
Data Element: TB example Data Element Name: Reason subject first came to medical attention Clinical Definition: The reason the subject was first medically evaluated for possible TB disease or latent TB infection. Valid Values: (enumerated) Symptoms Contact investigation Source case investigation Screening of High Risk Population Other (Specify) Unknown
Key Objectives Develop and publish an initial set of CV & TB specific data standards clinical data elements, definitions and value sets Leveraging CDISC and HL7 standards processes, focus on methodology for developing therapeutic area data standards using case studies Produce useful products for CV & TB and report experience, process and best practices
Parallel Universes Patient Care World Clinical Research World TB: Diagnosis & Treatment of Pulmonary TB CDISC Healthcare Link CDISC Standard Terminology EHR (health record) CDASH (data collection) SDTM (submission) BRIDG Model
Results CDISC & HL7 Artifacts Use cases and storyboards (H) Data elements and clinical definitions (U) Domain Class model (H) Domain Activity diagram (H) Data collection forms (R) SDTM representation (R) H = Healthcare / R = Research / U = Universal
TB Data Standards Working Group Aeras Global TB Vaccine Foundation (Gates funded) Centers for Disease Control & Prevention (CDC) CDISC Duke University Med. Center FIND Diagnostics (Gates funded) Global TB Alliance (Gates funded) Health Level 7 National Cancer Institute National Heart, Lung & Blood Institute (NHLBI) National Institute of Allergy and Infectious Diseases (NIAID) National TB Control Assoc. Otsuka Tibotec (a J&J company) WHO Stop TB Partnership Other Global Pharmas
CDISC operates to advance the continued improvement of public health by enabling efficiencies in medical research and related areas of healthcare. 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.