Margaret Haber Co-Director Enterprise Vocabulary Services National Cancer Institute

1. HL7 RCRIM Vocabulary Update:Standards Available or in Development Through NCI Enterprise Vocabulary Services (EVS) Margaret Haber Co-Director Enterprise Vocabulary Services National Cancer Institute http://evs.nci.nih.gov/

2. NCI EVS: Goals & Services • Goals • Meet the controlled terminology needs of NCI and its partners. • Promote semantic integration of clinical, translational and basic research, administrative, and public information systems. • Services • Controlled Terminologies • NCI Thesaurus: logic-based, rapid-response reference terminology. • NCI Metathesaurus: cross-link meanings from 60+ terminologies. • Standalone terminologies: MedDRA, LOINC, SNOMED, GO, etc. • Partnerships & Tools • Develop term sets & standards: FedMed, CDISC, HL7, CHI/FHA,… • Sharable tools: Share ours, help develop open-source tools.

3. NCI Thesaurus (NCIt) • Reference terminology for NCI and its partners. • Semantic reference for caCORE/caBIG metadata and models. • A Federal standard terminology used in NCI, NIH, other systems. • Richly structured content for people and computers • >58,000 concepts with >200,000 synonyms and codes. • >37,000 text definitions. • >200,000 “role” relationships semantically connect concepts. • Description logic classifier uses roles to check concept hierarchies. • Directly incorporates terms and codes from closely integrated partners, e.g., FDA, CDISC, caDSR.

4. NCI Thesaurus (2) • Broad coverage of cancer and other clinical and research related subject areas. • Neoplastic and other diseases, findings and abnormalities. • Anatomy, tissues, subcellular structures. • Agents, drugs, chemicals. • Genes, gene products, biological processes. • Clinical & research procedures, tools, trials, management, etc. • Animal models – mouse, other. • Rapid updates & freely available. • Published monthly, with pre-release available during test cycle. • Available via Web browsers, program APIs, downloadable files in OWL, Ontylog XML, and flat file formats. • Public domain, open content license.

5. NCI Thesaurus: Browser Example

6. NCI EVS Partner Content Integration NCI Thesaurus concept for Pharmaceutical Dosage Form showing harmonization of partner content from FDA and CDISC using defined subsets.

7. NCIt: Basis for the NCI Drug Dictionary

8. Mapping Terminologies: NCI Metathesaurus • Access to and cross-links between 60+ terminologies. • 1,200,000 concepts, 2,700,000 terms and phrases, with definitions. • Extensive synonymy, e.g. 7,000 neoplasm concepts provide over 40,000 synonym terms from many sources. • Based on NLM’s UMLS Metathesaurus, dropping less useful sources and adding special purpose terminologies. • Integrates access to key terminologies: NCI Thesaurus, the ICD’s, MedDRA, SNOMED, MeSH (NLM Medical Subject Headings), HCPCS (procedures), LOINC (lab values), drugs (VA NDF, AOD, RxNORM, Multum, etc.), science (GO, HUGO, OMIM, JAX, KEGG, NCBI), etc. • Frequent updates, freely available • Publish minor releases monthly, major releases 2-3 times a year. • Mostly open content, with some source licence restrictions. • Available via public browsers, APIs, and flat file formats.

9. NCI Metathesaurus: Browser Example

10. NCI EVS: Semantic Base of caCORE Bioinformatics Infrastructure & caBIG • cancer Bioinformatics Infrastructure Objects (caBIO) • UML Object Models • Applications & APIs • cancer Data Standards Repository (caDSR) • ISO 11179 metadata repository • Common Data Elements (CDEs) for forms etc. • Enterprise Vocabulary Services (EVS) • Core semantics • APIs • Browsers biomedical objects common data elements controlled vocabulary

11. NCI EVS: Extending Interoperability • Developing collaborations beyond NCI. • Federal: FDA, VA, CDC, other NIH Institutes. • Major standards organizations: HL7, CDISC, W3C. • Cancer Centers and Cooperative Groups: caBIG, caGRID. • Research collaborators such as the Microarray Gene Expression Data Society (MGED). • Some areas of collaboration. • FDA (drugs, devices, and clinical trials). • VA (drugs, clinical trials semantics, terminology operations). • CDC (cancer incidence and prevention, terminology operations). • Cancer Centers & caBIG (clinical trials, experimental organisms, micro-nutrients, open terminology servers). • CDISC/HL7 RCRIM (clinical research and health care data standards).

12. Some Current Projects and Collaborations • CDISC terminology hosting, production and publication: SDTM and beyond • Other NIH IC’s such as NHLBI and NIH “Roadmap” grant projects • FDA required and regulatory terminology including • SPL (Structured Product Label) • ICSR (Individual Case Safety Report) • CDRH device and safety related terminology such as for MedWatch reporting • UNII’s (> 1,500 Unique Ingredient Identifiers) • Regulated Product Submission terminology in early development

13. FDA Standards Hosted in NCIt (NCI Thesaurus) • For SPL: • Limitation of Use • Pharmacokinetic Effect Consequences • (Product) Color • DEA Schedule • Drug Route of Administration • Medical Product Intent of Use • Package Type • Pharmaceutical Dosage Form • (Product) Potency • (Product) Shape • Type of Drug Interaction Consequence

14. FDA Standards Hosted in NCIt (2) • For the ICSR: • Adverse Event Outcome • Location of Event Occurrence • Occupation • Operator of Medical Device • Device Usage • Report Source • Type of Event • Type of Follow-Up • Reason for Non-Evaluation • Type of Manufacturer • Type of Remedial Action • Type of Report

15. FDA Standards Hosted in NCIt (3) • Terminology for the Centers for Device and Radiological Health (CDRH): transformation of current CDRH terminology lists of codes into targeted taxonomies, in order to create a foundation for asserted knowledge on medical device associated events including • Patient Conditions • Medical Device Components or Accessories • Medical Device Failures or Malfunctions • Regulated Product Submission Terminology for use by CDER, CBER, CDRH in early development

16. FDA Subsets in NCIt: • FDA_Subsets: • Patient_Problem_Codes_FDA_CDRH • Medical_Device_Component_Or_Accessory_Terminology_FDA _CDRH • Medical_Device_Problem_Codes_FDA_CDRH • Limitation_Of_Use_Structured_Product_Labeling_Terminology • Pharmacokinetic_Effect_Consequences_Structured_Product_Labeling_Terminology • Structured_Product_Labeling_Color_Terminology • Structured_Product_Labeling_DEA_Schedule_Terminology • Structured_Product_Labeling_Drug_Route_of_Administration_Terminology • Structured_Product_Labeling_Medical_Product_Intent_Of_Use_Terminology • Structured_Product_Labeling_Package_Type_Terminology • Structured_Product_Labeling_Pharmaceutical_Dosage_Form_Terminology • Structured_Product_Labeling_Potency_Terminology • Structured_Product_Labeling_Shape • Structured_Product_Labeling_Terminology • Structured_Product_Labeling_Type_Of_Drug_Interaction_Consequence_Terminology

17. FDA subsets in NCIt (2) • Type_of_Event_ICSR_Terminology • Type_Of_FollowUp_ICSR_Terminology • Type_Of_Manufacturer_ICSR_Terminology • Type_Of_Remedial_Action_ICSR_Terminology • Type_Of_Report_ICSR_Terminology • Type_of_Reportable_Event_ICSR_Terminology • Type_Of_Reporter_ICSR_Terminology • Adverse_Event_Outcome_ICSR_Terminology • Reason_For_Non-Evaluation_ICSR_Terminology • Report_Source_ICSR_Terminology • Occupation_ICSR_Terminology • Operator_of_Medical_Device_ICSR_Terminology • Location_Of_Event_Occurrence_ICSR_Terminology • Device_Usage_ICSR_Terminology • Individual_Case_Safety_Report_Terminology Current total of more than 5,000 standardized electronic FDA tagged concepts in NCI Thesaurus representing well over 10,000 FDA terms and codes.

18. Using the NCIt Report Writer • The Report writer is a desktop application that retrieves concept data from the production version of the NCIt. • The application file, named ReportWriter.zip, is available from the anonymous FTP site: ftp://ftp1.nci.nih.gov/pub/cacore/EVS/fda/ • The application will retrieve all concepts in any Subset such as CDISC • Concepts in every Subset will be identified by the Concept_in_Subset association • A complete list of the available Subsets from the terminology server will be retrieved • From this list the user will choose the desired Subset • The application will retrieve all the concepts in the selected Subset and output them as a flat file or XML file

19. NCI EVS Partnerships: CDISC • Clinical Data Interchange Standards Consortium (CDISC) • 1997- Global organization for clinical data standards & exchange. • Creates open, platform-independent, global standards with participation of private and public organizations. • 2004- CDISC Controlled Terminology Team began defining terminology standards underlying Study Data Tabulation Model (SDTM). • CDISC Terminology Team a close NCI EVS partner. • Joint effort to specify and develop broadly based clinical trials standard terminology, based on CDISC models. • NCI Thesaurus adopted as CDISC terminology development and publication environment. • CDISC is also developing metadata in the NCI Data Standards Repository, using EVS terminology as foundation. • Open CDISC standards, developed in collaboration with FDA, NIH, HL7 and others, can provide the basis for a controlled terminology set shared across the clinical trials community.

20. SDTM Package 1 Terminology 1. Action Taken with Study Treatment 2. AE Severity / Intensity 3. Age Span 4. Age Units 5. Country 6. Dictionary Name 7. Domain Abbreviation 8. Ethnicity 9. Formulation (Dose) 10. Inclusion/Exclusion Category 11. Non -Completion Reason 12. Not Done 13. No / Yes Responses 14. Outcome of Event 15. Route of Administration 16. Sex 17. Sex of Participants 18. Size 19. System Organ Class 20. Relation to Reference Period 21. Trial Blinding Schema 22. Trial Type of Control 23. Trial Diagnosis Group 24. Trial Indication Type 25. Toxicity Grade 26. Trial Phase 27. Trial Summary Parameters 28. Type of Trial 29. Vital Signs Tests 30. Vital Signs Units

21. SDTM Package 2 Terminology • 8 additional SDTM domains including Findings – EG, PE, VS, SC; Interventions – CM, EX, SU; and Events – AE’s • ECG Test Results • Physical Examination • Vital Signs • Subject Characteristics • Concomitant Medications • Exposures • Substance Use • Adverse Events

22. NCI EVS: Open Products & Services • EVS Web site:http://evs.nci.nih.gov/ • Web terminology servers: • NCI Thesaurus & Standalone: http://nciterms.nci.nih.gov/ • NCI Metathesaurus: http://ncimeta.nci.nih.gov/ • API: http://ncicb.nci.nih.gov/core/caBIO/ • Software developed by EVS is free & open source: http://ncicb.nci.nih.gov/core/ • NCI Thesaurus is open content:ftp://ftp1.nci.nih.gov/pub/cacore/EVS/ThesaurusTermsofUse.htm • NCI Metathesaurus is mostly open content: See Each Source’s License athttp://ncimeta.nci.nih.gov/MetaServlet/GenerateSourcesServlet

23. Contact:Margaret W. HaberCo-DirectorNCI Enterprise Vocabulary ServicesNCI Office of the Directormhaber@mail.nih.govhttp://evs.nci.nih.gov