Margaret Haber, RN, OCN Co-Director Enterprise Vocabulary Services National Cancer Institute RCRIM Vocabulary and Controlled Terminology for Clinical Research.

Margaret Haber, RN, OCN Co-Director

Enterprise Vocabulary ServicesNational Cancer Institute

RCRIM Vocabulary and Controlled Terminology for

Clinical Research

Clinical Research Challenges• Fundamental new capacities to

characterize and intervene in biological systems and the disease process

• Hampered by our inability to integrate huge volumes of data due to information fragmentation

• Many diverse research and delivery platforms that are disconnected due to a lack of common, interoperable systems and semantics

• The problem is International in scope, and with enormous implications for our ability to translate information into knowledge

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 and among enterprises

The Pillars of InteroperabilityNecessary but not sufficient

Common information models across all domains of interestA foundation of rigorously defined data types (metadata)A methodology for interfacing with controlled vocabularies

Interoperability Keys for Terminology

Use of Industry Standards, where feasible Must allow for extensions to core standards Specialty terminology remains common Mapping is therefore essential

Conformance with Data Models For process (logical models) For data flow (messages) For data at rest (database design)

Clinical Data Interchange Standards Consortium (CDISC)

CDISC is an open, multidisciplinary, non-profit organization committed to the development of worldwide industry standards to support the electronic acquisition, exchange, submission and archiving of clinical trials data and metadata for medical and biopharmaceutical product development.

HL7 (Health Level Seven)

HL7 is a volunteer, ANSI-accredited Standards Developing Organization (SDO) that focuses on clinical and administrative healthcare data.

Mission:"To provide standards for the exchange, management and integration of data that support clinical patient care and the management, delivery and evaluation of healthcare services. Specifically, to create flexible, cost effective approaches, standards, guidelines, methodologies, and related services for interoperability between healthcare information systems.“

Bringing It All

Together: RCRIM • The HL7 “Regulated Clinical Research Information Management” Technical Committee formed as a collaboration of CDISC, FDA, and HL7

To facilitate the development of common standards for clinical research information management across a variety of organizations, including government agencies, private research efforts, and sponsored research

To develop standards for interchange of regulated data that are interoperable with general healthcare standards.

HL7 Vocabulary (including RCRIM)

Value sets associated with certain domain portions of HL7 modelsMost vocabulary domains are published as informative references onlyThose domains that have a formal ballot status are shown in bold in the HL7 vocabulary tables on their web siteThere are current initiatives to map these values to standard controlled terminologies

HL7 Vocabulary - Access

HL7 publishes at http://www.hl7.org/library/data-model/RIM/C30204/vocabulary.htmThere are approximately 8,000 terms or “concepts” in the current HL7 vocabularyScroll down to select a specific “table” or set of termsAlso available through an NCI developed “HL7 SDK” (software development kit) application toolConversion notes are included, see “HL7_Design.pdf” on NCI’s website

What’s Happening Now?CDISC, RCRIM and NCI

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) Using the NCI Data Standards Repository (caDSR), which draws controlled terminology from NCI EVS systems, including but not limited to leveraging NCI Thesaurus resources for novel terminology development

Collaboration

These open standards, developed in collaboration with FDA, NIH, HL7 and industry experts, can provide the basis for a controlled terminology set submitted to HL7 RCRIM as proposed standards for adoption by the clinical trials community

Where? NCI EnterpriseVocabulary Services (EVS)

Services and resources that address NCI and Partner’s needs for controlled vocabulary http://evs.nci.nih.gov/ A collaboration NCI Office of Communications

Physician Data Query (PDQ), Clinical Trials Portal, Cancer Information Service and the NCI web portal www.cancer.gov

NCI Center for Bioinformatics Bioinformatics Core Infrastructure

(caCORE), including a metadata repository (caDSR) and object models built using EVS terminology for their 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 frameworksCreate 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.

NCI Thesaurus (NCIt)

Reference Terminology for NCI, PartnersA Federal Standard TerminologyBroad coverage of the cancer, other 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 trials, lab, radiology, imagery

NCI Thesaurus (2)

Published MonthlyPublic domain, open content licenseAvailable on-line and by download (OWL, Ontylog XML, flat files)55,000+ “Concepts” hierarchically organizedDescription-logic based “Roles” establish machine readable semantic relationships between Concepts

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NCI Thesaurus is Deployed:

http://nciterms.nci.nih.gov

http://www.nci.nih.gov/EVS (full documentation)• API: caCORE public access• Fulfills NCI and collaborators’ needs

for controlled vocabulary• Public domain, open content license

Example Disease Concept

Gastric Mucosa-Associated Lymphoid Tissue Lymphoma  A low grade, indolent B-cell lymphoma, usually associated with Helicobacter Pylori

infection. Morphologically it is characterized by a dense mucosal atypical lymphocytic (centrocyte-like cell) infiltrate with often prominent lymphoepithelial lesions and plasmacytic differentiation. Approximately 40% of gastric MALT lymphomas carry the t(11;18)(q21;q21). Such cases are resistant to Helicobacter Pylori therapy. -- 2003

Molecular abnormalities:Disease_May_Have_Cytogenetic_Abnormality: Trisomy 3Disease_May_Have_Cytogenetic_Abnormality: Trisomy 18Role group 1:

Disease_May_Have_Cytogenetic_Abnormality: t(11;18)(q21;q21)Disease_May_Have_Molecular_Abnormality: AP12-MLT fusion protein expression

Histogenesis:Disease_Has_Normal_Cell_Origin: Post-germinal center marginal zone B-lymphocyte

Pathology:Disease_Has_Abnormal_Cell: Centrocyte-like cellDisease_May_Have_Abnormal_Cell: Neoplastic monocytoid B-lymphocyteDisease_May_Have_Abnormal_Cell: Neoplastic plasma cellDisease_May_Have_Finding: Lymphoepithelial lesion

 Anatomy:

Disease_Has_Primary_Anatomic_Site: StomachDisease_Has_Normal_Tissue_Origin: Gut associated lymphoid tissue

 Clinical information:

Disease_May_Have_Finding: Indolent clinical courseDisease_May_Have_Associated_Disease: Hepatitis C

A holistic view of information exchange also requires broader interoperability, but where do we place the fences?

Clinical data, regulatory submissions, discovery research?Industry agreements, nationally accredited, global standardization?

One answer is mapping: Relating Terminologies for

Effective Data Exchange

Mapping: NCI Metathesaurus

A filtered version of the NLM UMLS Metathesaurus, extended with additional required vocabularies 1,100,000 concepts, 2,200,000+ terms

and phrases with definitions Mappings among over 55 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 two to three times 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.)

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NCI Metathesaurus: Browser Example

EVS Products & Services Are Open

NCI Thesaurus is Open Content ftp://ftp1.nci.nih.gov/pub/cacore/EVS/ThesaurusTermsofUse.htmNCI Metathesaurus is Mostly Open SourceSee Each Source’s License http://ncimeta.nci.nih.gov/MetaServlet/GenerateSourcesServletNCI 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:

http://nciterms.nci.nih.gov and http://ncimeta.nci.nih.gov

http://ncicb.nci.nih.gov/core/caBIO

http://ncicb.nci.nih.gov/core

NCI builds on EVS via caCORE Infrastructure

Enhanced Information integrationCross-discipline

reasoning capabilities

biomedical objects

common data elements

controlled vocabulary

Enterprise VocabularyNCI Meta-Thesaurus (Cross-mapped standard vocabularies, e.g. ICD’s, MedDRA, SNOMED)

Semantic integration, inter-vocabulary mapping among 55+ vocabularies

UMLS Metathesaurus extended with numerous additional vocabularies

1,100,000+ Concepts, 2,200,000 terms and phrases

NCI Thesaurus Description logic-based 55,000+ “Concepts”

Concept is the semantic unit One or more terms describe a

Concept – synonymy Semantic relationships between

Concepts

Freestanding terminologies MedDRA, MGED, NDF-RT, GO, SNOMED, etc.

biomedical objects

common data elements

controlled vocabulary

Common Data Elements (caDSR)

Structured data reporting elementsPrecisely 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

Controlled Terminology is integrated into NCI’s 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 11179 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

EVS: Extending Interoperability Beyond the Enterprise

Leverage Collaborations Federal: FDA, VA, CDC, other NIH

Institutes Major Standards Organizations: HL7,

CDISC, W3C Cancer Centers and Cooperative Groups

(caBIG, caGRID) Many research collaborators such as the

Microarray Gene Expression Data Society (MGED)

FDA-NCI MOUSignificance of MOU NCI is leveraging its terminology-related

resources to address FDA needs Avoids expenditure at FDA to replicate existing,

available resources at NCI, increases 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 broader clinical trials community

FDA and NCI are to coordinate regarding terminology standards efforts such as HL7 RCRIM (including CDISC)

Example:NCI EVS and FDA SPL

NCI EVS maintains and provides access to FDA SPL TerminologyNCI Thesaurus will be a primary namespace usedAlso FDA standard terminology for the ICSR, IND/NDA, device nomenclature, others Access Via

Download at ftp://ftp1.nci.nih.gov/pub/cacore/EVS/ Public, open API http://ncicb.nci.nih.gov/core/caBIO Web Servlet at http://nciterms.nci.nih.gov

Concept DetailsURI: http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?

dictionary=NCI_Thesaurus&code=C42887Version: December 30, 2004 (04.12g)

Aerosol Dosage FormIdentifiers: name Aerosol_Dosage_Form code C42887Information 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 valvesystem; it is intended for topical application to theskin as well as local application into the nose(nasal aerosols), mouth (lingual aerosols), or lungs (inhalation aerosols).

Synonym with source data AER|AB|FDA_CDER|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 Synonym Aerosol Dose FormSuperconcepts:

Pharmaceutical Dosage FormSubconcepts:

Aerosol Foam Dosage FormAerosol Spray Dosage FormMetered Aerosol Dosage FormPowder Aerosol Dosage Form

This indicates the concept is used in the FDA Structured Product Label (SPL)

A Vital Collaboration:CDISC and NCI –Shared models, metadata standards, and core semantics drawn from standard terminology

CDISC terminology group is working with NCI tools through EVS for the specification and development of broad based clinical trials standard terminology, based on CDISC models CDISC is using the NCI Data Standards Repository and controlled terminology from NCI EVS, including but not limited to NCI Thesaurus, for novel terminology developmentThese open CDISC standards, developed in collaboration with FDA, NIH, HL7 and others, can provide the basis for a controlled terminology set able to be adopted across the clinical trials community

NCIt Browser: CDISC Tagged Concept

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Terminology concept for Race showing harmonization of different users, including CDISC, NCI, CDC, etc.

NCI ThesaurusConcept: Race

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Benefits of Terminology Development in a Common Environment

A Step Towards Semantic Interoperability

• Support and maintenance of terminologies in NCI EVS provides access to and common usage of standard terminologies

• Enables use of controlled terminology by clinicians and researchers for data encoding, retrieval, reporting, and aggregation

• Facilitates collaboration and information exchange by increasing the ability to predictably use information that is gathered

• Leverages the power of shared knowledge

You can collaborateJoint Participation: In standards groups such as HL7 RCRIM in order to inform relevant standards decisionsJoint Development: Contributing to clinical trials standard terminology development efforts, i.e. through CDISC terminology groupProviding validation and testing: Content and modeling developed with industry input is more robust, better able to meet your needs, and you can better plan/anticipate implementation/impacts on your organization

Participate in HL7 RCRIM

The HL7 “Regulated Clinical Research Information Management” Technical Committee, formed as a collaboration of CDISC, FDA, and HL7

To facilitate the development of common standards for clinical research information management across a variety of organizations -- including government agencies, private research efforts, and sponsored research

To develop standards for interchange of regulated data that are interoperable with general healthcare standards.

Contact:Margaret W. Haber, RN, OCNCo-DirectorNCI Enterprise Vocabulary ServicesNCI Office of the [email protected]://evs.nci.nih.gov/