CDISC Standards: Connecting Clinical Research and Healthcare NCBO Meeting Signs, Symptoms and...

CDISC Standards: Connecting Clinical Research and Healthcare

NCBO MeetingSigns, Symptoms and Findings3 September 2008, Dallas TX

Bron Kisler (CDISC)Gary Walker (Quintiles)

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.

CDISC operates to advance the continued improvement of public health by enabling efficiencies in medical research and related areas of healthcare.

CDISC Standards Description Implementation Version Release Date

SDTM, SEND Ready for regulatory submission of CRT

Over 10,000 downloads as of late-20072004*

ODM CDISC Transport Standard for data interchange (acquisition, exchange, documentation and archive)

2001*

Define.xml Case Report Tabulation Data Definition Specification (submission documentation)

2005*

LAB Content standard – available for transfer of clinical lab data to sponsors

2002

ADaM Analysis data for submissions - general considerations document and examples

2004

Protocol

Representation

Collaborative effort to develop machine-readable standard protocol with data layer

Fall 2008

Terminology

Codelists

Developing standard terminology to support all CDISC standards

2006-07 Package1 2007-08 Package2

CDASH Data acquisition (CRF) standards Sept. 2008

* Specification referenced via FDA Final Guidance

Data Flow Using CDISC Standards

Study &Analysis

Data

Study & Analysis

Data

Reporting orRegulatory

SubmissionsWarehouse

(e)SourceDocument

Operational & Analysis

Databases

Patient Info

CDASH-eCRF Study Data(defined by

SDTM)

ODMXML

ODM XMLDefine.xml

ODMXML

Lab DataIntegratedReports

Trial DesignAnalysis Plan

Study Protocol

ProtocolRepresentation

= SDTM - Study Data Tabulation Model and ADaM - Analysis Dataset Model (content)SEND for Non-clinical Data

= ODM - Operational Data Model (transport of data and metadata…”the message”)

= Protocol Representation Standard (content)

= Source data (other than SDTM/CRF data)= LAB – Laboratory Data Standard

Interventions

Exposure

Conmeds

SubstUse

Findings

VitalsLabs

ECG

Incl/Excl SubjChar

Ques’aire

Micro MSMicro MB

DrugAcctPhysExam

PK ParamPK Conc

Events

AE

Deviations

Disposition

MedHx

ClinicalEvents

Demog

Special Purpose

Comments

SUPPQUAL

Trial Design (5 Tables)

RELREC

SubjElements

SubjVisits

Submissions – SDTM version 3.1.2

SDTM = Study Data Tabulation ModelSDTM = Study Data Tabulation Model

SDTM General Observation Classes

Interventions class captures investigational, therapeutic and other treatments that are administered to the subject (with some actual or expected physiological effect) either as specified by the study protocol (e.g., “exposure”), coincident with the study assessment period (e.g., “concomitant medications”), or self-administered by the subject (such as alcohol, tobacco, or caffeine)

Events class captures planned protocol milestones such as randomization and study completion (“disposition”), and occurrences, conditions or incidents independent of planned study evaluations occurring during the trial (e.g., “adverse events”) or prior to the trial (e.g., “medical history”)

Findings class captures the observations resulting from planned evaluations to address specific tests or questions such as laboratory tests, histopathology, ECG testing, and questions listed on questionnaires. Most findings are measurements, tests, assessments, or examinations performed on a subject in the clinical trial

CDISC Terminology Snapshot

• Formalized CDISC Terminology Initiative in 2005

• Primary Objective: to define and support the terminology needs of the CDISC models across the clinical trial continuum (SDTM → CDASH)

• Focus on “standard” terminology development and publication, beginning with SDTM ver3.1.1

• Key partnership with US National Cancer Institute Enterprise Vocabulary Services (NCI EVS)

• External harmonization: ISO, HL7 RCRIM, FDA, HITSP, NCI, etc.

CDISC Controlled Terminology

NCI Thesaurus

LOINC

SNOMED

MedDRA

MeSH

ICD’s

.

.

.

60+Controlled

Vocabularies

http://www.cancer.gov/index.html

9

• CDISC-led Project (initiated by ACRO) to address FDA Critical Path Initiative Opportunity #45

• Mission: To develop a set of ‘content standards’ (element name, definition, metadata) for a core set of global data collection fields that will support clinical research studies.

• Scope: The initial scope is focused on the ‘safety data/domains’ common across all therapeutic areas

• Process: Begin with and map to SDTM version 3.1.1; focus on ‘CRF content’ not layout; collect CRF samples and id commonalities; work with Terminology Team on terminology proposals; follow CDISC consensus process

Clinical Data Acquisition Standards Harmonization

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CDASH Collaborative Group

• American Medical Informatics Association (AMIA)

• Association of Clinical Research Organizations (ACRO)

• Association of Clinical Research Professionals (ACRP)

• Baylor College of Medicine• Biotechnology Industry

Organization (BIO)• Clinical Data Interchange

Standards Consortium (CDISC)• Clinical Research Forum• Critical Path Institute • Duke Clinical Research Institute

(DCRI)

• Food & Drug Administration (FDA)• NIH - NCI - caBIG • NIH - Clinical Research Policy

Analysis & Coordination Program• National Clinical Research

Resources (NCRR)• NIH - National Institute of Child

Health & Human Development (NICHD)

• National Library of Medicine (NLM)

• Pharmaceutical Research and Manufacturers Association (PhRMA)

• Society for Clinical Data Management (SCDM)

CDASH-ODM Connection

Creating CDASH-ODM Template

<ODM><Study>

<Meta …</Meta …

</Study></ODM>

CDASH–ODMTemplate

CDASH Content

SDTM - Study DataTabulation Model

TerminologyCodelists

PresentationExtended ODM

ODM - OperationalData Model

(Database Contentand Structure)

ODM Building BlocksHow does CDASH Relate?

Clinical DatabaseVariable Name CDASH CRF

Label/Question CDASH Core (Highly Recommended)

Controlled Terminology

Optimal Solution from Standardized Content to any EDC System

CDASH Content

Controlled Terminology

Codelists

Therapeutic Specific Content

InternalData Standards

<ODM><Study>

<Meta…</Meta…

</Study></ODM>

Vendor NeutralPortable Format

Study DesignIn ODM

+

Extended ODM

Proprietary System

Features

System A

System B

System C

Multi-Vendor Visualizations – PhaseForward

Multi-Vendor Visualizations - Medidata

CDISC ‘Healthcare Link’

18

Study & Analysis

Data

Clinical Trial Data

Study &Analysis

Data

Patient Info

RegulatorySubmissions

(e)SourceDocument

Operational & Analysis

Databases

Electronic Health Record

Patient Info

CDASH-eCRF) Study Data(defined by

SDTM)

ODMXML

ODM XMLDefine.xml

ODMXML

HL7 and/orODM XML

Lab Data

IntegratedReports

Study DesignAnalysis Plan

Study Protocol

ProtocolRepresentation

HL7 and/orODM XML

= SDTM and Analysis Data (content)

= ODM (transport)

= Protocol information (content)

= Source data (other than SDTM/CRF data)

Data Flow Using CDISC Standardslinking clinical research & healthcare

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Workflow Integration: RFD

EHREHR

Clinical Research Sponsor

Case Report Form (CRF)• CDASH• ODM

Data ArchiverStores the electronic source document

Data ReceiverReceives the data instance from the Form Filler.

Forms ManagerServes up the form to the Form Filler.

Forms FillerDisplays the form for completion in an EHR session

RFD = Retrieve Form for Data CaptureRFD = Retrieve Form for Data Capture

DataArchiver

FormManager

3. Form Manager pre-populates Lilly S001 form and returns to Form Filler who completes and submits the form

20

DataReceiver

RFD

FormFiller

CernerCernerMillenniuMillenniu

mm

RFD Proof of Concept

Lilly/Quintiles 4. Data ReceiverReceives and inserts data into Phase Forward’s Clintrial CDMS.

1. Site Investigator uses Cerner Millenium to retrieve an electronic case report form.

5. Data Archiver stores the electronic source document.

2. Form Filler forwards CDASH data elements to the Form Manager (to retrieve a pre-populated form)

•CDASH data elements (demographics, AE, meds) hit 25/33 slots in Lilly CRF. •ODM + XForms allowed 4 EHRs to render the form on the first try!

Other Healthcare Links

CDISC Standards & BRIDG Model(Biomedical Research Information Domain Group)

Submissions

Analysis Data

SDTM / SEND

Glossary

ODM

LAB

ADaM

CDASH

Data Collection

Protocol

BRIDG is amechanism

for standardsintegration

BRIDG as a portal to Healthcare

Submissions

Analysis Data

SDTM / SEND

Glossary

ODM

LAB

ADaM

CDASH

Data Collection

Protocol

Healthcare

HL7 RIM

BRIDG

BRIDG

BRIDG Domain Analysis Model(implementation independent)

cd Comprehensive Model

Clinical Research Entities and Roles::Agent

+ id: CodedConcept+ name: string+ description: string+ status: CodedConcept+ formCode: CodedConcept+ lotNumber: int+ expirationDate: DATETIME+ stabilityTime: DATETIME

Clinical Research Entities and Roles::

AgentRole


FundingSponsor


HealthCareSite


Investigator

+ certificateLicenseText:

Clinical Research Entities and Roles::Organization

+ id: CodedConcept+ name: string+ description: string+ status: CodedConcept+ statusDate: DATETIME+ geographicAddr: addrType+ telecomAddr: TEL

Clinical Research Entities and Roles::OrganizationRole

Clinical Research Entities and Roles::Participant

+ paymentMethod: CodedConcept+ confidentialityCode: string

Clinical Research Entities and Roles::Person

+ id: CodedConcept+ administrativeGenderCode: BRIDGCodedConcept+ dateOfBirth: DATETIME+ raceCode: BRIDGCodedConcept+ ethnicGroupCode: BRIDGCodedConcept+ maritalStatusCode: BRIDGCodedConcept+ electronicCommAddr: + householdIncomeCategory: BRIDGCodedConcept+ educationLevelCode: BRIDGCodedConcept+ telecomAddress: TEL+ name: entityName+ dateOfDeath: DATETIME+ address: addrType

Clinical Research Entities and Roles::PersonRole

::Role+ id: CodedConcept+ code: CodedConcept+ status: + electronicCommAddr: + geographicAddr: + telecomAddr: + effectiveStartDate: DATETIME+ effectiveEndDate: DATETIME

Clinical Research Entities and Roles::TherapeuticAgent

Clinical Trials Activ ities::AdverseEvent

+ onsetDate: date+ resolvedDate: date+ ctcCategoryCode: string+ ctcCategoryCodeSystem: string+ ctcTermTypeCode: string+ ctcTermTypeCodeSystem: string+ ctcAttributionCode: string+ ctcAttributionCodeSystem: string+ ctcGradeCode: string+ ctcGradeCodeSystem: string+ seriousReasonCode: string+ outcomeCode: string+ actionTakenCode: string+ conditionPatternCode: string+ doseLimitingToxicityIndicator: boolean+ doseLimitingToxicityDescriptionText: string+ descriptionText: string

Clinical Trials Activ ities::

AdverseEventReport

+ id: int+ submissionDate: date+ fi ledIndicator: boolean

Clinical Trials Activ ities::AdverseEventTherapy

+ id: int+ treatmentDate: date+ delayDuration: int+ delayDurationUnitOfMeasureCode: string+ intensityCode: string

Clinical Trials Activities::Assessment

+ id: int+ evaluationDate: date


AssessmentRelationship

+ id: int+ typeCode: string+ commentText: string

Clinical Trials Activ ities::CancerStage

+ id: int+ tnmStage: string+ tnmStageCodeSystem: string+ stageCode: string+ stageCodeSystem: string

Clinical Trials Activ ities::ClinicalResult

+ panelName: string+ value: string+ valueUnitOfMeasureCode: string+ assayMethodCode: string+ bodyPositionCode: string+ labReferenceRangeCode: string+ labTechniqueCode: string+ meansVitalStatusObtainedCod: string+ abnormalIndicator: boolean+ biomarkerInd: boolean+ significanceInd: boolean

Clinical Trials Activ ities::DeathSummary

+ deathDate: date+ deathCauseCode: char+ deathCauseText: string+ autopsiedIndicator: boolean

Clinical Trials Activ ities::Diagnosis

+ name: string+ diseaseDiagnosisCode: string+ diseaseDiagnosisCodeSystem: string+ ageAtDiagnosis: int+ confirmationDate: date+ primaryAnatomicSiteCode: string+ primaryAnatomicSiteCodeSystem: string+ primaryAnatomicSiteLateralityCode: string+ recurrenceIndicator: boolean+ diseaseStatusCode: string+ sourceCode: string+ sourceOther: string+ diseaseExtentText: string

Clinical Trials Activ ities::DiseaseResponse

+ responseCode: char+ responseCodeSystem: string+ bestResponseCode: char+ bestResponseDate: date+ progressionDate: date+ progressionPeriod: int+ progressionPeriodUnitOfMeasureCode: string+ doseChangeIndicatorCode: int+ courseDispositionCode: string+ commentText: string

Clinical Trials Activ ities::Histopathology

+ grossExamResultCode: string+ reportDescriptiveText: string+ involvedSurgicalMarginIndicator: boolean

Clinical Trials Activ ities::HistopathologyGrade

+ id: int+ gradingSystemName: string+ grade: string+ comments: string

Clinical Trials Activ ities::Imaging

+ identifier: string+ contrastAgentEnhancement: string+ descriptiveText: string+ rateOfEnhancementValue: int

Clinical Trials Activ ities::LesionDescription

+ lesionNumber: string+ evaluationNumber: int+ appearanceTypeCode: string+ targetNonTargetCode: string+ measurableIndicator: boolean+ methodCode: string+ xDimension: int+ yDimension: int+ zDimension: int+ dimensionProduct: int+ anatomicSiteCode: string+ anatomicSiteCodeSystem: string+ contactAnatomicSiteCode: string+ contactAnatomicSiteCodeSytem: string+ previouslyIrradiatedSiteIndicator: boolean Clinical Trials

Activ ities::LesionEvaluation

+ evaluationCode: char

Clinical Trials Activ ities::MetastasisSite

+ id: int+ anatomicSiteCode: string+ anatomicSiteCodeName: string

Clinical Trials Activ ities::Neoplasm

+ id: int+ cellType: string

Clinical Trials Activ ities::Observation

+ id: int+ reportingDate: date+ confidentialityCode: string+ uncertaintyCode: string+ statusCode: string


ObservationRelationship

+ id: int- type: string+ comments: string

Clinical Trials Activ ities::PerformedActiv ity

+ plannnedUnplannedInd: boolean::Activity+ code: PSMCodedConcept+ derivationExpression: TEXT+ description: PSMDescription+ startDate: DATETIME+ status: PSMCodedConcept+ availabilityTime: TimingSpecification+ priorityCode: PSMCodedConcept+ confidentialityCode: PSMCodedConcept+ repeatNumber: rangeOfIntegers+ interruptibleIndicator: BOOLEAN+ uncertaintyCode: CodedConcept+ reasonCode: PSMCodedConcept+ endDate: DATETIME

Clinical Trials Activ ities::PerformedStudy

+ id: BRIDGID+ longTitle: string+ shortTitle: string+ phaseCode: ENUM+ intentCode: ENUM+ monitorCode: ENUM+ blindedInd: boolean+ randomizedInd: boolean+ diseaseCode: CodedConceptDataType+ sponsorCode: CodedConceptDataType+ multiInstitutionInd: boolean+ targetAccrualNumber: int

Clinical Trials Activ ities::PlannedActiv ity

::Activity+ code: PSMCodedConcept+ derivationExpression: TEXT+ description: PSMDescription+ startDate: DATETIME+ status: PSMCodedConcept+ availabilityTime: TimingSpecification+ priorityCode: PSMCodedConcept+ confidentialityCode: PSMCodedConcept+ repeatNumber: rangeOfIntegers+ interruptibleIndicator: BOOLEAN+ uncertaintyCode: CodedConcept+ reasonCode: PSMCodedConcept+ endDate: DATETIME

Clinical Trials Activ ities::PlannedStudy

::Activity+ code: PSMCodedConcept+ derivationExpression: TEXT+ description: PSMDescription+ startDate: DATETIME+ status: PSMCodedConcept+ availabilityTime: TimingSpecification+ priorityCode: PSMCodedConcept+ confidentialityCode: PSMCodedConcept+ repeatNumber: rangeOfIntegers+ interruptibleIndicator: BOOLEAN+ uncertaintyCode: CodedConcept+ reasonCode: PSMCodedConcept+ endDate: DATETIME

Clinical Trials Activ ities::Procedure

+ targetSiteCode: string

Clinical Trials Activ ities::QualitativeEvaluation

+ survivalStatusCode: int+ survivalStatusDescriptionText: string+ performanceStatusCode: int- performanceStatusCodeSystem: string+ painIndexCode: int+ painIndexCodeSystem: string+ anamResultAccuracyPercent: int+ menstrualPatternTypeCode: string+ menstrualIndicator: boolean

Clinical Trials Activ ities::Radiation

+ therapyType: string+ doseUnitOfMeasure: string+ dose: string

Clinical Trials Activ ities::Specimen

+ id: int+ idNumber: int+ samplingType: string


SpecimenCollection

+ siteCondition: string+ method: string

Clinical Trials Activ ities::StudyAgent

::Participation+ type: CodedConcept+ status: CodedConcept+ statusDate: DATETIME+ startDate: DATETIME+ endDate: DATETIME

Clinical Trials Activ ities::StudyInvestigator

+ signatureCode: int+ signatureText: string::Participation+ type: CodedConcept+ status: CodedConcept+ statusDate: DATETIME+ startDate: DATETIME+ endDate: DATETIME

Clinical Trials Activ ities::StudySite

+ targetAccrualNumber: int::Participation+ type: CodedConcept+ status: CodedConcept+ statusDate: DATETIME+ startDate: DATETIME+ endDate: DATETIME

Clinical Trials Activ ities::SubjectAssignment

+ studySubjectIdentifier: int+ arm: string+ subgroupCode: string+ informedConsentFormSignedDate: date+ offStudyDate: date+ studyAgentDoseLevel: string+ eligibilityWaiverReason: string+ ageAtEnrollment: int::Participation+ type: CodedConcept+ status: CodedConcept+ statusDate: DATETIME+ startDate: DATETIME+ endDate: DATETIME

Clinical Trials Activ ities::SubstanceAdministration

+ doseQuantity: int+ doseUnitOfMeasure: string+ route: string+ doseFrequency: string+ doseModificationType: string+ doseChangeType: int


Surgery

BRIDG Shared Classes::Activity

+ code: PSMCodedConcept+ derivationExpression: TEXT+ description: PSMDescription+ startDate: DATETIME+ status: PSMCodedConcept+ availabilityTime: TimingSpecification+ priorityCode: PSMCodedConcept+ confidentialityCode: PSMCodedConcept+ repeatNumber: rangeOfIntegers+ interruptibleIndicator: BOOLEAN+ uncertaintyCode: CodedConcept+ reasonCode: PSMCodedConcept+ endDate: DATETIME

BRIDG Shared Classes::Activ ityActiv ityRelationship

+ relationshipCode: PSMCodedConcept- Obsolete_relationQualifier: BRIDGCodedConcept+ sequenceNumber: NUMBER+ pauseCriterion: + checkpointCode: + priorityNumber: NUMBER+ splitCode: - negationRule: AbstractRule+ joinCode: + negationIndicator: BOOLEAN+ conjunctionCode:

BRIDG Shared Classes::Participation

+ type: CodedConcept+ status: CodedConcept+ statusDate: DATETIME+ startDate: DATETIME+ endDate: DATETIME

BRIDG Shared Classes::Role

+ id: CodedConcept+ code: CodedConcept+ status: + electronicCommAddr: + geographicAddr: + telecomAddr: + effectiveStartDate: DATETIME+ effectiveEndDate: DATETIME

BRIDG Shared Classes::RoleRoleRelationship

+ source: + type: CodedConcept+ target:

BRIDG Shared Classes::BRIDGAnalysisVariable

+ name: TEXT+ value: + controlledName: PSMCodedConcept+ businessProcessMode: PSMBusinessProcessMode

BRIDG Shared Classes::BRIDGBusinessProcessMode

+ modeValue: ENUM {Plan, Execute}

BRIDG Shared Classes::BRIDGCodedConcept

- code: TEXT- codeSystem: - codeSystemName: TEXT- codeSystemVersion: NUMBER- displayName: TEXT- originalText: TEXT- translation: SET{PSMCodedConcept}

BRIDG Shared Classes::BRIDGContactAddr

+ type: BRIDGCodedConcept+ effectiveTime: BRIDGInterval+ usage: BRIDGCodedConcept

BRIDG Shared Classes::BRIDGDescription

+ synopsis: EncapsulatedData+ summaryDescription: EncapsulatedData+ detailedDescription: EncapsulatedData

BRIDG Shared Classes::BRIDGID

+ source: Text+ version: Text+ value: Text

BRIDG Shared Classes::BRIDGInterval

- startTime: timestamp+ endTime: timestamp

BRIDG Shared Classes::BRIDGStatus

+ effectiveEndDate: + effectiveStartDate: + statusValue:

Protocol Concepts::StudyDocument

+ version: string+ author: SET+ ID: SET BRIDGID+ documentID: BRIDGID+ type: ENUM+ description: BRIDGDescription+ title: string+ status: BRIDGStatus+ confidentialityCode: CodedConcept

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FDA IT Plan (CDISC-HL7 Message)

MedWatch AE Reports (ICSR)

JanusFDA/NCI

Analytical DataWarehouse

FDA Reviewers

Trial Design

Sponsor Data

Warehouse(ODM)

Data Checker

and Loader

Review Tools

Sponsor

Site DataArchive(ODM)

Site

Interchange:HL7 output fileCDISC Content and Interchange CDISC Content

CDASH

SDTMADaM

CDISC Standards: Connecting Clinical Research and Healthcare NCBO Meeting Signs, Symptoms and...

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