Margaret Haber, RN, OCN Frank Hartel, PhD Enterprise Vocabulary Services National Cancer Institute Overview of NCI Enterprise Vocabulary Services (EVS) and Semantic Integration at NCI

Outline: Terminology management and semantic integration at NCI NCI Enterprise Vocabulary Services NCI Thesaurus (NCIt) NCI Metathesaurus Collaboration FDA – NCI MOU and IOTF CDISC and NCI

NCI biomedical informatics Goal: A virtual web of interconnected data, individuals, and organizations redefines how research is conducted, care is provided, and patients/participants interact with the biomedical research enterprise

in·ter·op·er·a·bil·i·ty ability of a system...to use the parts or equipment of another system Source: Merriam-Webster web site interoperability ability of two or more systems or components to exchange information and to use the information that has been exchanged. Source: IEEE Standard Computer Dictionary: A Compilation of IEEE Standard Computer Glossaries, IEEE, 1990] Interoperability Semantic interoperability Syntactic interoperability Courtesy: Charlie Mead

No Controlled Terminology? No Interoperability Systems cannot exchange or use information if they use incompatible codes or tokens to signify meaning Terminology services provide token and codes Proper use of them assures consistent meaning across the enterprise

Vocabulary for CDE specification Dictionary, thesaurus, ontology services via caBIO API Domain object metadata Common data elements Public APIs Common data elements (CDEs) Can it be done? caCORE - An Example via downloads

Information integration Cross- discipline reasoning cancer Common Ontologic Representation Environment (caCORE) biomedical objects common data elements controlled vocabulary

Common Data Elements Structured data reporting elements Precisely defining the questions and answers What question are you asking, exactly? What are the possible answers, and what do they mean? biomedical objects common data elements controlled vocabulary

Biomedical Information Objects Data service infrastructure developed using OMG’s Model Driven Architecture approach Object models expressed in UML represent actual biomedical research entities such as genes, sequences, chromosomes, sequences, cellular pathways, ontologies, clinical protocols, etc. The object models form the basis for uniform APIs (Java, SOAP, HTTP-XML, Perl) that provide an abstraction layer and interfaces for developers to access information without worrying about the back-end data stores biomedical objects common data elements controlled vocabulary

Enterprise Vocabulary NCI Metathesaurus (Cross-map standard vocabularies/ontologies, e.g. SNOMED, MedDRA, ICD) Semantic integration, inter-vocabulary mapping UMLS Metathesaurus extended with cancer-oriented vocabularies  930,000 Concepts, 2,200,000 terms and phrases  Mappings among over 50 vocabularies NCI Thesaurus Description logic-based 48,000 “Concepts”  Concept is the semantic unit  Terms are Concept labels – synonymy  Semantic relationships between Concepts Other standard terminologies MedDRA, MGED, SNOMED, GO, etc. biomedical objects common data elements controlled vocabulary

NCI builds on EVS via caCORE Infrastructure

Production EVS Servers in caCORE

Enterprise Vocabulary Services Services and resources that address NCI's needs for controlled vocabulary A collaboration NCI Office of Communications  Physician Data Query (PDQ), Cancer Information Service and the NCI web portal NCI Center for Bioinformatics  Bioinformatics Core Infrastructure (caCORE), including metadata repository (caDSR) and object models built using EVS terminology for core semantics

NCI EVS Goal – Integration by Meaning Clinical, translational, and basic research terminology have overlapping but specialized needs, therefore EVS assists to:  Integrate different conceptual frameworks  Create terminological and taxonomic conventions across systems Vocabulary Products NCI Thesaurus – an ontology-like terminology NCI Metathesaurus – maps vocabularies External vocabularies maintained and served: MedDRA, HL7, NDF-RT, LOINC, etc.

Terminology Development Guidelines Develop a content model Leverage existing sources where appropriate (VA NDF-RT, RxNorm, LOINC, etc. …) Develop unique content where needed (Cancer genes and diagnoses, drugs and therapies, molecular abnormalities, clinical trial standard terminology etc.) Link to other information sources and standards using URLs as possible (GO, Swissprot, drug formularies, trial protocols) Merge with or map as needed to other standard terminology to ensure interoperability

NCI Thesaurus (NCIt) Reference Terminology for NCI, Partners A Federal Standard Terminology Broad coverage of the cancer research and clinical domain including prevention and treatment trials Neoplastic and other Diseases Findings and Abnormalities Anatomy, Tissues, Subcellular Structures Agents, Drugs, Chemicals Genes, Gene Products, Biological Processes Animal Models – Mouse, other Research techniques and management, apparatus, clinical and lab, radiology, imagery

NCI Thesaurus (2) Published Monthly Public domain, open content license Available on-line and by download (OWL, Ontylog XML, flat files) 48,000+ “Concepts” hierarchically organized Description-logic based “Roles” establish machine readable semantic relationships between Concepts, ex.: “Carcinoma” Clinically_associated_with “Lytic Bone Lesions,” “TP53” Gene_associated_with_Disease “Breast Carcinoma”

NCI Thesaurus is Deployed: (full documentation) API: caCORE public access Fulfills NCI and collaborators’ needs for controlled vocabulary Public domain, open content license

Example Concept Details Concept Details URI: Version: July 2005 (05.07d) Aerosol Dosage Form Identifiers: name Aerosol_Dosage_Form code C42887 Information about this concept: Synonym with source data Aerosol Dosage Form|PT|NCI Synonym AER Synonym Aerosol Synonym with source data Aerosol Dose Form|SY|NCI Synonym Aerosol Dosage Form DEFINITION FDA|A product that is packaged under pressure and contains therapeutically active ingredients that are released upon activation of an appropriate valve system; it is intended for topical application to the skin as well as local application into the nose (nasal aerosols), mouth (lingual aerosols), or lungs (inhalation aerosols). FDA_Table Dosage Form (C-DRG-00201) Synonym with source data Aerosol|PT|FDA|246 Preferred_Name Aerosol Dosage Form Synonym with source data AER|AB|FDA|246 Semantic_Type Manufactured Object Synonym Aerosol Dose Form Superconcepts: Gas Dosage Form Topical Dosage Form Subconcepts: Aerosol Foam Dosage Form Aerosol Spray Dosage Form Metered Aerosol Dosage Form Powder Aerosol Dosage Form This indicates the concept is an FDA concept used in the SPL This indicates the FDA table in which the concept occurs

Other Examples : Use URI to view Details of a Drug Concept- ser/ConceptReport.jsp?dictionary=NCI_ Thesaurus&code=C620 ser/ConceptReport.jsp?dictionary=NCI_ Thesaurus&code=C620 Use GUI to search for and view hierarchy Fluvastatin Sodium

NCI Metathesaurus: Filtered UMLS Metathesaurus extended with additional required vocabularies 930,000+ concepts, 2,200,000 terms and phrases with definitions Mappings among over 50 vocabularies Extensive synonymy: Over 40,000 terms for neoplasms mapped to 7,000 concepts Used as online dictionary and thesaurus, for mapping and document indexing

NCI Metathesaurus (2) Minor releases monthly, Major releases twice a year Provides a mapped overlap and partial inter- relation of current versions of NCI and partner required vocabularies, ex. The ICD’s, MedDRA, SNOMED, MeSH (NLM Medical Subject Headings), HCPCS (procedures), LOINC (lab values), drug terminologies (VA NDF-RT, AOD, RxNORM, Multum, NCI Thesaurus drugs, etc.)

EVS Products & Services Are Open NCI Thesaurus is Open Contnent ftp://ftp1.nci.nih.gov/pub/cacore/EVS/ThesaurusTer msofUse.htm ftp://ftp1.nci.nih.gov/pub/cacore/EVS/ThesaurusTer msofUse.htm NCI Metathesaurus is Mostly Open Source See Each Source’s License cesServlet NCI EVS Servers Are Freely Accessible On the Web : Via API : All Software Developed by NCI EVS is Public Open Source and Free for the Asking: and

EVS Collaborations Many Active Collaborations Federal: FDA, VA, CDC, and Various NIH Institutes such as NHLBI, NIDCR Major Standards Organizations: HL7, CDISC, W3C Cancer Centers and Cancer Cooperative Groups (caBIG, caGRID) Numerous Research collaborators such as the Microarray Gene Expression Data Society (MGED)

Areas of Collaboration FDA (Terminology for Drugs, Devices, and Clinical Trial Terminology Initiatives) VA (Drugs, Common Clinical Trials Semantics, Terminology Operations) CDC (Cancer Incidence and Prevention, Terminology Operations) Cancer Centers (Clinical Trials, Experimental Organism Terminology, Micro- nutrients, Open Terminology Servers, other (caBIG)) CDISC/HL7 RCRIM (Clinical Research Data Standards)

FDA-NCI MOU Significance of MOU Avoids expenditure at FDA to replicate existing, available resources at NCI Increased return on investment for NIH/NCI Leverages multiple efforts FDA collaboration with NIH/NCI will result in improved trial drug and related regulatory terminology for the cancer and broader clinical trials community Complementary to the CDISC/NCI collaboration on terminology requirements for CDISC models such as the Study Data Tabulation Model (SDTM)

Scope of MOU Establishes a formal mechanism for FDA and NCI to collaborate on mutually beneficial projects related to clinical research terminology Enumerates resources that can be shared - joint terminology development, evaluation, and maintenance, best practices - shared tools, techniques, hardware, software, networks

Scope of MOU - concluded Under the MOU: NCI to leverage terminology-related resources to address FDA needs FDA and NCI to coordinate regarding relevant terminology standards and standards development efforts such as those of the HL7 RCRIM technical committee FDA and NCI are to identify opportunities to employ consistent terminology, and terminology practices, especially in support of CHI/FHA initiatives/goals and eGOV

Example: NCI EVS and FDA SPL NCI EVS will maintain and provide access to FDA SPL Terminology NCI Thesaurus will be the namespace used Access Via  Download at ftp://ftp1.nci.nih.gov/pub/cacore/EVS/ ftp://ftp1.nci.nih.gov/pub/cacore/EVS/  Public, open API  Web Servlet at

CDISC Collaboration CDISC terminology group has established an independent working environment at NCI for the specification and development of broad based clinical trials standard terminology, based on CDISC models (SDTM) CDISC is using the NCI Data Standards Repository (caDSR metadata repository), and controlled terminology from NCI EVS, including but not limited to NCI Thesaurus resources for novel terminology development These open CDISC standards, developed in collaboration with FDA, NIH, HL7 and others, can provide the basis for a controlled terminology set to be broadly adopted as standard in the clinical trials community

Benefits of the CDISC-NCI Collaboration The opportunity to develop shared models, metadata standards, and core semantics drawn from standard terminology, such as NCIt and other EVS hosted vocabularies, in order to: Ensure the validity of cross study data comparison and analysis Improve the efficiency, evaluation of safety and efficacy, and time to approval for treatments (increased patient safety and reduced cost) Improve the links between primary healthcare delivery systems and clinical research and trials

NCI Thesaurus Browser: CDISC tagged concepts

NCI Thesaurus Browser: concept- “Race”

Contact: Margaret W. Haber, RN, OCN NCI Office of Communications Frank Hartel, PhD NCI Center for Bioinformatics

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Binding Data, Metadata to Terminology - caCORE SDK UML Modeling Tool (provided by user) Information model that will define data classes, attributes and relationships Semantic Connector Annotate UML model with ontology concepts: bridges the world of databases to that of structured semantics. UML Loader (run by NCI staff) Loads model into the caDSR metadata registry Model and associated semantics are available at runtime Code Generator Model and a code template are inputs into generator Creates the ‘caCORE-like’ n-tier software system with Java and Web Services APIs

caCORE SDK

Extending Interoperability Beyond the Enterprise cancer Biomedical Informatics Grid (caBIG) Common, widely distributed infrastructure permits cancer research community to focus on innovation Shared vocabulary, data elements, data models facilitate information exchange Collection of interoperable applications developed to common standard Raw cancer research data is available for mining and integration

caBIG - facilitate sharing of infrastructure, applications, and data

Cancer Center Cancer Center NCI caGrid OTHER caBIG SERVICE PROVIDERS OTHER TOOLKITS

caGrid Service-Oriented Architecture Grid Communication Protocol Service Description Service Business Process Service Registry Security Semantic Service Resource Management Functions Quality of Service ID Resolution OGSA Compliant - Service Oriented Architecture Transport GSI CAS myProxy Globus DQPWorkflow OGSA-DAIGlobusGRAM Globus Toolkit caCORE Mobius Globus

NCI caDSR tool: CDE Browser

CDE Browser: CDISC Context

CDE Browser: Vital Signs CDEs CDEs and Metadata for CDISC context

Demo CDEs and Metadata for CDISC context CDE Browser: Demo CDISC Context CDEs

CDE for Race

CDE: Race- permissible values

EVS Concept Linkage

NCI Terminology Browser: Tree Race Race Subconcepts (Includes OMB required classes)

March 12, 2004Columbia52 EVS is part of caCORE Infrastructure Deployed (Real) Integrative, Experimental, Collaborative Scaleable, End-to- End Production Process

Access to NCI Thesaurus via APIs

NCI standards supporting infrastructure Enterprise Vocabulary Services (EVS) Core Semantics for caCORE and many other applications Public access browsers APIs cancer Data Standards Repository (caDSR) ISO metadata repository Common Data Elements (CDE’s) for multiple templates, such as Case Report Forms, drawn from EVS terminology cancer Bioinformatics Infrastructure Objects (caBIO) UML Models annotated with EVS concepts/terms, loadable into caDSR Public access APIs

cancer Common Ontologic Representation Environment (caCORE) Enhanced Information integration Cross-discipline reasoning capabilities biomedical objects common data elements controlled vocabulary

Enterprise Vocabulary NCI Meta-Thesaurus (Cross-map standard vocabularies/ontologies, e.g. SNOMED, MedDRA, ICD) Semantic integration, inter-vocabulary mapping UMLS Metathesaurus extended with cancer-oriented vocabularies  930,000 Concepts, 2,200,000 terms and phrases  Mappings among over 50 vocabularies NCI Thesaurus Description logic-based 48,000 “Concepts”  Concept is the semantic unit  One or more terms describe a Concept – synonymy  Semantic relationships between Concepts biomedical objects common data elements controlled vocabulary

Common Data Elements (caDSR) Structured data reporting elements Precisely defined, harmonized questions and answers Standardized questions for forms Standard lists of coded valid values for answers biomedical objects common data elements controlled vocabulary

Biomedical Information Objects (caBIO) UML object models representing clinical and research entities such as genes, sequences, chromosomes, pathways, etc. Public access APIs provide an information interface independent of back-end data platforms biomedical objects common data elements controlled vocabulary

March 12, 2004Columbia59 NCI Thesaurus is Deployed: (full documentation) API: caCORE public access Fulfills NCI and collaborators’ needs for controlled vocabulary Public domain, open content license

Some Details Several NIH Institutes are using NCI EVS for specific projects NLM and HL7 planning to use NCI infrastructure in EMR demonstration project caBIG seen as by ONCHIT as a pilot for aspects of National Health Information Network

Concept Details URI: dictionary=NCI_Thesaurus&code=C42887 Version: December 30, 2004 (04.12g) Aerosol Dosage Form Identifiers: name Aerosol_Dosage_Form code C42887 Information about this concept: Preferred_Name Aerosol Dosage Form Semantic_Type Manufactured Object DEFINITION FDA|A product that is packaged under pressure and contains therapeutically active ingredients that are released upon activation of an appropriate valve system; it is intended for topical application to the skin as well as local application into the nose (nasal aerosols), mouth (lingual aerosols), or lungs (inhalation aerosols). Synonym with source data AER|AB|FDA|246 Synonym with source data Aerosol Dosage Form|PT|NCI Synonym with source data Aerosol|PT|FDA|246 Synonym AER Synonym Aerosol Synonym Aerosol Dosage Form Superconcepts: Dosage Form Subconcepts: Aerosol Foam Dosage Form Aerosol Spray Dosage Form Metered Aerosol Dosage Form Powder Aerosol Dosage Form This indicates the concept is an FDA concept used in the SPL

Concept Details URI: dictionary=NCI_Thesaurus&code=C42887 Version: December 30, 2004 (04.12g) Aerosol Dosage Form Identifiers: name Aerosol_Dosage_Form code C42887 Information about this concept: Preferred_Name Aerosol Dosage Form Semantic_Type Manufactured Object DEFINITION FDA|A product that is packaged under pressure and contains therapeutically active ingredients that are released upon activation of an appropriate valve system; it is intended for topical application to the skin as well as local application into the nose (nasal aerosols), mouth (lingual aerosols), or lungs (inhalation aerosols). Synonym with source data AER|AB|FDA|246 Synonym with source data Aerosol Dosage Form|PT|NCI Synonym with source data Aerosol|PT|FDA|246 Synonym AER Synonym Aerosol Synonym Aerosol Dosage Form FDA TableDosage Form (DRG ) Superconcepts: Dosage Form Subconcepts: Aerosol Foam Dosage Form Aerosol Spray Dosage Form Metered Aerosol Dosage Form Powder Aerosol Dosage Form This indicates the FDA table in which the concept occurs