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
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
10
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)
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
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
19
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!
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
Clinical Research Entities and Roles::
FundingSponsor
Clinical Research Entities and Roles::
HealthCareSite
Clinical Research Entities and Roles::
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
Clinical Trials Activ ities::
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
Clinical Trials Activ ities::
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
Clinical Trials Activ ities::
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
Clinical Trials Activ ities::
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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+target activity
«abstraction»
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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