BRIDG Basics

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What is BRIDG?Biomedical Research Integrated Domain Group

• A formal model

• A communication bridge

• An open community of stakeholders

• The semantic foundation for application and message development

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How did BRIDG get started? • Four important streams of development came together

– CDISC: In early 2004, CDISC started constructing a Domain Analysis Model to support harmonization of their standards for clinical research as well as with the Health Level Seven (HL7) healthcare standard.

– NCI: In late 2004, NCI's Cancer Biomedical Informatics Grid (caBIG™) initiative joined the CDISC BRIDG efforts to construct a structured protocol representation for its Clinical Trials Management Systems (CTMS) Workspace, in order to further interoperability among clinical trials research in cancer.

– HL7: In 2005, the BRIDG model was adopted by the HL7 Regulated Clinical Research Information Management (RCRIM) Technical Committee as the RCRIM Domain Analysis Model.

– FDA: In 2007, the US Food and Drug Administration included BRIDG in their 5 year IT Plan as a foundation for several projects.

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BRIDG Scope

BRIDG Scope: Protocol-driven research and its associated regulatory artifacts,

i.e. the data, organization, resources, rules, and processes involved in the formal assessment of the utility, impact, or other pharmacological, physiological, or psychological effects of a drug, procedure, process, subject characteristic, biologic, cosmetic, food or device on a human, animal, or other subject or substance plus all associated regulatory artifacts required for or derived from this effort, including data specifically associated with post-marketing adverse event reporting.

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BRIDG Governance

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•BRIDG Board of Directors

•BRIDG Semantic Coordination Committee

Current Governance of the BRIDG Model BRIDG Board of Directors

• BRIDG Board of Directors– Representation from the current stakeholders– Helps to set priorities and identify resources

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BRIDGBoard of Directors

NCI

Academia

Pharma Industry

CDISC

HL7FDA

Source: Doug Fridsma

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BRIDG Board of Directors

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Appointed Members

Charlie Mead NCIBron Kisler CDISCChuck Jaffe HL7Jay Levine FDA

At Large Members Term Expiration

Becky Kush* 2011John Speakman 2013Jack Jones 2011Cecil Lynch 2012AbdulMalik Shakir 2012Diane Wold 2013Sub Dubman 2013

* Chair

Current Organization of the BRIDG SCC

• Semantic Coordination Committee (SCC)– Responsible for ongoing model maintenance– Harmonizes subdomain projects into the main model

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BRIDGSemantic Coordination Committee

caBIG HL7CDISC FDA

Source: Doug Fridsma

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Semantic Coordination Committee (SCC)

Name Affiliation

Charlie Mead NCI / Booz & CompanySteve Sandberg NCI / ScenPro, Inc.Mike Woodcock NCI / Mayo ClinicSmita Hastak NCI / ScenPro, Inc.Wendy Ver Hoef NCI / ScenPro, Inc.Becky Angeles NCI / ScenPro, Inc.Julie Evans CDISCLloyd McKenzie NCI / Gordon Point Informatics

The BRIDG Model

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Perspectives of BRIDG

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Perspectives of BRIDG

• Recognize and support the different types of BRIDG users

• Each perspective is intended for a different audience

• Each perspective is a representation of the same semantics

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BRIDG Canonical Perspective

• Comprehensive Domain Analysis Model (DAM)

• Intended for information analysts• Single UML model• Modeled and managed in Enterprise Architect

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BRIDG Canonical PerspectiveModel of Subject

class BRIDG Domain Analysis Mo...

Common Sub-Domain::StudySubject{leaf}

+ confidentialityIndicator: BL+ paymentMethodCode: CD+ statusCode: CD+ statusDate: TS.DATETIME::Subject+ state: ST+ actualIndicator: BL

Common Sub-Domain::StudySubjectIdentifier

+ identifier: II+ typeCode: CD+ effectiveDateRange: IVL<TS.DATETIME>

Common Sub-Domain::Subject{root}

+ state: ST+ actualIndicator: BL

+identifying

0..*

identifies

{is identified by}

+identified

1

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BRIDG Comprehensive View – Canonical Perspective

Protocol Representation

Adverse Event

Study Conduct

Common Regulatory

BRIDG SME Perspective

• Domain-friendly layer• Intended for the subject matter experts (also

called business users or domain experts)• Multiple UML models, one for each sub-

domain• Modeled and managed in Enterprise Architect• Automatically generated from Canonical

Perspective

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BRIDG SME PerspectiveAdverse Event Sub-Domain Model of

Subject

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class View AE: Adv erse Ev ...

Common Sub-Domain::Investigativ eSubject

{root}

+ state: ST

constraints{Is a Function Performed By Exclusive Or}

Common Sub-Domain::StudySubject

{leaf}

+ confidentialityIndicator: BL+ paymentMethodCode: CD+ statusCode: CD+ statusDate: TS.DATETIME::InvestigativeSubject+ state: ST

BRIDG HL7 Perspective

• RIM-based model• Intended for message developers• Modeled in HL7 proprietary modeling

methodology and developed in Visio• Single DMIM-like model• Maps to UML-based model• Manually generated from Canonical

Perspective

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BRIDG HL7 PerspectiveModel of Subject

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BRIDG Semantic Perspective

• Several ontological representations• OWL-DL format• Intended for semantic validation and

inferencing

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BRIDG Semantic PerspectiveModel of Subject

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class View AE: Adv erse Ev ...

Common Sub-Domain::Investigativ eSubject

{root}

+ state: ST

constraints{Is a Function Performed By Exclusive Or}

Common Sub-Domain::StudySubject

{leaf}

+ confidentialityIndicator: BL+ paymentMethodCode: CD+ statusCode: CD+ statusDate: TS.DATETIME::InvestigativeSubject+ state: ST

BRIDG as a global, public standard

• CDISC Review and Comment Process resulted in BRIDG as a CDISC standard in January 2010

• ISO Joint Initiative Council (JIC) Ballot Process – first round in May 2010 – BRIDG passed the ballot in both ISO and HL7 – next round starts in December 2010– ISO– HL7– CDISC

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BRIDG Content – 1(starting with most recent release)

Release Project Stakeholder

R3.0.3 Clinical Data Acquisition Standards Harmonization (CDASH) V1.1

CDISC

Study Data Tabulation Model (SDTM) V3.1.2 CDISC

Integrated Case Safety Report (ICSR) R2 FDA

R3.0.2 caBIG® Central Clinical. Participant Registry (C3PR) v2.9 NCI

Cancer Adverse Event Reporting System (caAERS) v2.2 NCI

Patient Study Calendar (PSC) v2.6 NCI

LabViewer v2.2 NCI

R3.0.1 Clinical Trials Registration and Results HL7 RCRIM

R3.0 (Architecture Redesign only)

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Release Project StakeholderR2.2 CDISC HL7 Message Study Design (partial) FDA

CDISC HL7 Message Study Participation FDAR2.1 Clinical Trial Registry (COPPA, ct.gov, WHO, PRV1.0) CDISC, NCI

Protocol Abstraction (COPPA – Correlations, Organizations, People and Protocol Abstraction)

NCI

R2.0 Adverse Events CDISC, NCI, NIH, US Federal Gov’t, FDA

Player / Scoper for Person and Org NCI, CDISCPatient Registry (C3PR) NCI

R1.1 Study Data Tabulation Model (SDTM) CDISCTrial Design Model CDISC

R1.0 Regulated Product Submission (RPS) FDA/HL7 RCRIM Patient Study Calendar (PSC) NCIClinical Trial Object Model (CTOM) NCIcaXchange/LabHub NCI/HL7RCRIM TC/CDISC

BRIDG Content - 2

A Bit More About the Canonical and SME Perspectives

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Unified Modeling Language

• Used in the BRIDG model via a modeling tool called Enterprise Architect

• The industry-standard language for specifying, visualizing, constructing, and documenting the requirements of software systems

• The BRIDG model uses these UML diagrams: – Class diagrams– Instance diagrams– State transition diagrams

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UML Class Diagrams

class – a concept of primary importance the domain-of-interest, depicted as a rectangle labeled with the concept’s name

attribute (including datatype specification) – a descriptive feature of a class, depicted as being contained within the class

relationship – one of several types of “lines” between classes

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Class diagram examplecd BRIDG Release 1.0

Employee

::Person- name: string

Company

- name: string

Person

- name: string

1..*

works for / employs

1

class

attribute

relationship

multiplicity

data type

BRIDG Class: StudyProtocolVersion

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BRIDG Class Definition: StudyProtocolVersion

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Definition of designConfigurationCode attribute

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Instance Diagrams

• “Instances” of class diagrams use sample data values to illustrate specific representational constructs

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class Adv erse Ev ent Sub-Dom...

Adv erseEv ent{leaf}

+ gradeCode: CD+ severityCode: CD+ seriousnessCode: CD+ categoryCode: CD+ subcategoryCode: CD+ occurrencePatternCode: CD+ endRelativeToReferenceCode: CD+ unexpectedReasonCode: DSET<CD>+ expectedIndicator: BL+ hospitalizationRequiredIndicator: BL+ highlightedIndicator: BL+ duration: PQ.TIME+ onsetDate: TS.DATETIME+ resolutionDate: TS.DATETIME::PerformedObservationResult+ identifier: II+ typeCode: CD+ result: ANY+ resultCodeModifiedText: ST+ targetAnatomicSiteCode: CD+ confidentialityCode: CD+ uncertaintyCode: CD+ reportedDate: TS.DATETIME+ comment: ST

Common Sub-Domain::StudySubject{leaf}

+ confidentialityIndicator: BL+ paymentMethodCode: CD+ statusCode: CD+ statusDate: TS.DATETIME::Subject+ state: ST+ actualIndicator: BL

Protocol Representation Sub-Domain::Study{root}

+ acronym: ST+ phaseCode: CD+ primaryPurposeCode: CD+ purposeStatement: ST+ diseaseCode: DSET<CD>+ targetAnatomicSiteCode: DSET<CD>+ designConfigurationCode: CD+ studySchematic: ED+ populationDescription: ST+ studySubjectTypeCode: CD+ plannedStudySubjectExperience: ST+ targetAccrualNumberRange: URG<INT>+ periodicTargetAccrualNumber: RTO<INT,PQ>+ accrualReportingMethodCode: CD+ responsiblePartyCode: CD+ participatingOrganizationTypeCode: CD+ participatingCountryCode: DSET<CD>+ aeCodingSystem: II+ multiInstitutionIndicator: BL

Study Conduct Sub-Domain::PerformedObserv ation

{leaf}

+ methodCode: DSET<CD>+ bodyPositionCode: CD+ targetAnatomicSiteCode: CD+ targetAnatomicSiteLateralityCode: CD+ /focalDuration: PQ.TIME+ /focalDateRange: IVL<TS.DATETIME>::PerformedActivity+ actualDuration: PQ.TIME+ actualDateRange: IVL<TS.DATETIME>+ /delayDuration: PQ.TIME+ missedReason: DSET<SC>+ missedIndicator: BL+ statusCode: CD+ statusDate: TS.DATETIME::Activity+ identifier: II+ reasonCode: DSET<CD>+ comment: ST

Study Conduct Sub-Domain::PerformedObserv ationResult

+ identifier: II+ typeCode: CD+ result: ANY+ resultCodeModifiedText: ST+ targetAnatomicSiteCode: CD+ confidentialityCode: CD+ uncertaintyCode: CD+ reportedDate: TS.DATETIME+ comment: ST

Common Sub-Domain::Subject{root}

+ state: ST+ actualIndicator: BL

Common Sub-Domain::Activity

{root}

+ identifier: II+ reasonCode: DSET<CD>+ comment: ST

Study Conduct Sub-Domain::PerformedObserv ation::PerformedActiv ity

{leaf}

+ actualDuration: PQ.TIME+ actualDateRange: IVL<TS.DATETIME>+ /delayDuration: PQ.TIME+ missedReason: DSET<SC>+ missedIndicator: BL+ statusCode: CD+ statusDate: TS.DATETIME::Activity+ identifier: II+ reasonCode: DSET<CD>+ comment: ST

Study Conduct Sub-Domain::StudySite

+ identifier: II+ leadIndicator: BL+ targetAccrualNumberRange: URG<INT>+ accrualStatusCode: CD+ accrualStatusDate: TS.DATETIME+ dateRange: IVL<TS.DATETIME>+ statusCode: CD+ statusDate: TS.DATETIME

+resulted

0..*

is a result of

{results in}

+producing

1

+involving 0..*

is participated in by

{participates in}

+involved 0..1

+contained

0..*

occurs inthe contextof

{providescontext to}

+containing 0..1

+executing

0..*

executes

{is executed at}

+executes

1

+assigned

0..*

is assigned to

{is the assigned location for}

+assigning 1

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class AE7 - Adv erse Ev e...

NABTC-06-02 :Study

Patient #7 :StudySubject

Extremity-lower :Adv erseEv ent

hospitalizationRequiredIndicator = NoonsetDate = 01/31/2008resolutionDate = 02/01/2008gradeCode.CD.code = 3gradeCode.CD.codeSystemVersion = 3.0gradeCode.CD.codeSystem = CTCAEactualDateRange.IVL<TS> = blankresult = Extremity-lower (gait/walking)

Muscle weakness :Adv erseEv ent

onsetDate = 01/31/2008resolutionDate = 02/01/2008gradeCode.CD.code = 3gradeCode.CD.codeSystem = CTCAEgradeCode.CD.codeSystemVersion = 3.0actualDateRange.IVL<TS>.high = blankresult = Muscle weakness, generalized or specific area

Death :Adv erseEv ent

hospitalizationRequiredIndicator = NoonsetDate = 02/12/2008resolutionDate = 02/12/2008gradeCode.CD.codeSystemVersion = 3.0gradeCode.CD.code = 5gradeCode.CD.codeSystem = CTCAEactualDateRange.IVL<TS>.high = blankresult = Death

NABTC 2 Pt 7 :StudySite

Assess symptom :PerformedObserv ation Assess symptom :PerformedObserv ation Assess symptom :PerformedObserv ation

Part of an Instance Diagram

State Transition Diagrams

• A State Transition Diagram illustrates how an element (often a Class) can move between states, classifying its behavior according to transition triggers and constraining guards.

• Also called State Machine Diagrams or State Charts

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State Transition Diagram – Study Subject

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stm Subject StateDiagr...

Potential Candidate Candidate

Eligible

On-Study

Off-Study

Ineligible

Initial

Final

Interv ention Observ ation

Withdraw consent (after on-study) typically would trigger a whole set of regulatuery related actions.

Follow-Up

Study defines the epochs and States define the transitions of the subject thru the study defined "epochs"

Screening

Pending On-Study

System Restriction: A regulatory problem is encountered if any data is captured on a person before informed consent is signed; so no research system would ever be allowed to capture people as Potential Candidates or Candiates - those are only logical states.

NOTE: We have not addressed the notion of minors. This may not change the diagram, it's just that consent is obtained from whoever has legal power to provide consent. Need to consider this.

Having the Intervention and Observation sub-states is helpful for reporting but may cause other problems. Observation may be called "short-term follow-up" at some institutions, i.e. they are coming back to the clinic for tests though they are no longer receiving the intervention.

Not Registered

Withdrawn

Study Subject Status DISCLAIMER: All state transition diagrams are rough and should be considered DRAFT.

screen failure

pooling

subject refusal

follow-up complete

death (adverse event)

study terminated

unable orunwill ing toparticipate

did not meet elig. criteria

study permanentlyclosed to accrual

enrolled or registered

withdraw consent

withdrawn consent

refuse consent

eliminate

informed consent signed

eliminate

inclusion

exclusion

enrolled or registered

eligible, butunable orunwill ing topariticpate:

pre-registered or slot reserved

exclusion

trt and/orobseravationcomplete

trt or obs complete

adverse event

non-compliance

subject refusal

adverse event

subject refusal

withdrawn consent

identification

Important Components of a Release

• The Model– UML Based Model in Enterprise Architect Model

– Sub-Domains and Comprehensive View

– RIM Based Model

• Users Guide and Release Notes• Change Lists• Mapping Spreadsheet

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User’s Guide

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• Section 1: Guide to the Reader• Section 2: Executive Summary• Section 3: The BRIDG Project and BRIDG Model• Section 4: The BRIDG Model: General

Considerations and Representational Conventions

• Section 5: Model Content• Section 6: Glossary• Section 7: Appendix

User’s Guide

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Release Notes

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Table of Contents1 Executive Summary1.1 BRIDG ISO Joint Initiative Council (JIC) Ballot1.2 BRIDG Definition1.3 BRIDG Project Stakeholders1.4 BRIDG Project Goals1.5 Definition of BRIDG Model Domain of Interest2 What’s New in Release 3.0.12.1 General changes in Release 3.0.12.2 Detailed Change Lists for Release 3.0.13 Files in R3.0.1 Package3.1 UML-Based Models3.2 RIM-based Models3.3 Report of Comprehensive UML-Based Model3.4 XMI of Comprehensive UML-Based Model3.5 Release Notes (this file)3.6 User’s Guide3.7 BRIDG Domain Analysis Static Model Style Guide3.8 BRIDG CDISC Comment Resolution Spreadsheet4 Known Issues

UML-based Model: Mappings to Source Projects Enterprise Architect

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UML-Based ModelMappings to Source Projects

RTF Report

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methodCode public :CD A coded value specifying the technique that is used to perform the procedure.For example, for a specimen collection, finger stick, veni puncture, Abdominal/ ascites effusion, Biopsy, Bronchial alveolar lavage (BAL), etc.For example, if procedure is cholecystectomy the method could be open or laparoscopic.

Map:CTOM = 'SpecimenAcquisition.methodCode'Map:Lab = 'SpecimenCollection.method'Map:SDTM IG = 'EG.EGMETHOD'Map:SDTM IG = 'LB.LBMETHOD'

Foundation of rigorously defined data types

• Simple vs Abstract• Simple: Character, String, Text, Numeric

• BRIDG uses ISO 21090 data type specification

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Datatypes: Complex

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ISO 21090: Healthcare Data TypesST = StringCD = Concept Descriptor (Coded Concept)DSET = unordered collection, unique valuesED = Encapsulated dataURG = Uncertain RangeRTO = RatioII = Instance Identifier

Some CD properties:•displayName•originalText•code•codeSystemName•codeSystemVersion•valueSet•And more

Interfacing with Controlled Vocabularies

• Plans to move BRIDG semantics into a controlled environment such as NCI’s EVS / caDSR

• BRIDG controlled vocabulary should integrate with existing stakeholder vocabulary

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What’s the Process?

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Project Team develops Domain Analysis Model, mapping spreadsheet, valid value listsProject Team involves BRIDG SCC early

Updated BRIDG Domain Analysis Model is created

Reps from project team meet with SCC toharmonize the project model into the BRIDG

The project to BRIDG mapping spreadsheet needs to be maintained

A Look at the Model in Enterprise Architect

• How to get to the version for review:http://www.cdisc.org/contentmgr/showdetails.php/

id/1938• How to get to the model on the internet

– www.bridgmodel.org– The gForge site:

• Release Files• News• Bug and enhancement trackers• Work in progress in Subversion

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www.bridgmodel.org

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A Look at the Model in Enterprise Architect

• How to open the model and look at basic components – Project Browser– Views– Class diagrams– State Transition Diagrams– Instance diagrams

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Enterprise Architect – Project Browser

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ProjectBrowser

Project Browser - Views

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Protocol Representation View

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Comprehensive View

Project Browser – State Transition Diagrams

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Project Browser – Instance Diagrams

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