CDISC Standards:
Connecting Clinical
Research and Healthcare
NCBO Meeting
Signs, Symptoms and Findings
3 September 2008, Dallas TX
Bron Kisler (CDISC)
Gary Walker (Quintiles)
CDISC operates to advance the continued improvement of public health
by enabling efficiencies in medical research and related areas of healthcare.
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 Standards
Description
Implementation
Version Release
Date
SDTM, SEND
Ready for regulatory submission of CRT
Over 10,000 downloads as of late-2007
2004*
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 machinereadable 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
= ODM - Operational Data Model (transport of
data and metadata…”the message”)
= SDTM - Study Data Tabulation Model and ADaM - Analysis Dataset Model (content)
SEND for Non-clinical Data
= Protocol Representation Standard (content)
= Source data
= LAB – Laboratory Data Standard
Protocol
Representation
Trial Design
Analysis Plan
Study
Protocol
(other than SDTM/CRF data)
Patient Info
ODM
XML
CDASH-eCRF
Study Data
(defined by
SDTM)
(e)Source
Document
Integrated
Reports
Lab Data
ODM
XML
Study &
Analysis
Data
Operational &
Analysis
Databases
ODM XML
Define.xml
Study &
Analysis
Data
Reporting or
Regulatory
Submissions
Warehouse
Submissions – SDTM version 3.1.2
Interventions
Events
Conmeds
AE
ECG
Ques’aire
Exposure
Disposition
Incl/Excl
SubjChar
SubstUse
MedHx
Findings
Labs
Vitals
Special
Purpose
Demog
Comments
SubjElements
SubjVisits
Deviations
PhysExam
DrugAcct
Clinical
Events
PK Conc
PK Param
RELREC
Micro MB
Micro MS
Trial Design
(5 Tables)
SDTM = Study Data Tabulation Model
SUPPQUAL
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
LOINC
SNOMED
MedDRA
MeSH
ICD’s
NCI Thesaurus
.
.
.
60+
Controlled
Vocabularies
Clinical Data Acquisition
Standards Harmonization
• 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
9
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)
10
CDASH-ODM Connection
Creating CDASH-ODM Template
CDASH Content
ODM - Operational
Data Model
Terminology
Codelists
<ODM>
<Study>
<Meta …
</Meta …
</Study>
</ODM>
(Database Content
and Structure)
CDASH–ODM
Template
Presentation
Extended ODM
SDTM - Study Data
Tabulation Model
ODM Building Blocks
How does CDASH Relate?
Clinical Database
Variable Name CDASH CRF
Label/Question
Controlled Terminology
CDASH Core
(Highly Recommended)
Optimal Solution from Standardized Content to any EDC System
CDASH Content
Extended
ODM
Study Design
In ODM
System A
Therapeutic
Specific
Content
Internal
Data Standards
<ODM>
<Study>
<Meta…
</Meta…
</Study>
</ODM>
Vendor Neutral
Portable
Format
+
System B
Proprietary
System
Features
Controlled
Terminology
Codelists
System C
Multi-Vendor Visualizations –
PhaseForward
Multi-Vendor Visualizations - Medidata
CDISC ‘Healthcare Link’
Data Flow Using CDISC Standards
linking clinical research & healthcare
Electronic
Health Record
= ODM (transport)
= SDTM and Analysis Data (content)
= Protocol information (content)
Patient Info
HL7 and/or
ODM XML
HL7 and/or
ODM XML
= Source data
Clinical Trial
Data
Protocol
Representation
Study Design
Analysis Plan
Study
Protocol
(other than SDTM/CRF data)
Integrated
Reports
Patient Info
Lab Data
ODM
XML
CDASH-eCRF)
Study Data
(defined by
SDTM)
(e)Source
Document
ODM
XML
Study &
Analysis
Data
Operational &
Analysis
Databases
ODM XML
Define.xml
Study &
Analysis
Data
Regulatory
Submissions
18
Workflow Integration: RFD
Clinical Research
Sponsor
Forms
Manager
Serves up the form
to the Form Filler.
Data Receiver
Receives the data
instance from the
Form Filler.
Case
Report
Form (CRF)
Forms Filler
• CDASH
• ODM
Displays the form for
completion in an
EHR session
EHR
Data Archiver
Stores the electronic
source document
RFD = Retrieve Form for Data Capture
19
RFD Proof of Concept
3. Form Manager
pre-populates Lilly
Form
S001 formManager
and
returns to Form
Filler who
completes and
submits the form
2. Form Filler
forwards CDASH
data elements Form
to the
Filler
Form Manager (to
retrieve a prepopulated form)
Lilly/Quintiles
•CDASH data
elements
RFD AE,
(demographics,
meds) hit 25/33 slots
in Lilly CRF.
•ODM + XForms
allowed 4 EHRs to
render the form on
theCerner
first try!
4. Data Receiver
Receives and
Data
inserts data into
Receiver
Phase Forward’s
Clintrial CDMS.
5. Data Archiver
Data
stores
the electronic
Archiver
source document.
Millennium
1. Site Investigator
uses Cerner Millenium
to retrieve an electronic
case report form.
20
Other Healthcare Links
CDISC Standards & BRIDG Model
(Biomedical Research Information Domain Group)
Submissions
Data Collection
Glossary
SDTM / SEND
ODM
CDASH
ADaM
LAB
Analysis Data
Protocol
BRIDG is a
mechanism
for standards
integration
BRIDG as a portal to Healthcare
Submissions
Data Collection
B
R
I
D
G
Glossary
SDTM / SEND
CDASH
ODM
Protocol
ADaM
LAB
Analysis Data
B
R
I
D
G
Healthcare
HL7 RIM
BRIDG Domain Analysis Model
(implementation independent)
cd Comprehensive Model
BRIDG Shared Classes::Participation
BRIDG Shared Classes::Role
+
+
+
+
+
+
+
+
id: CodedConcept
code: CodedConcept
status:
electronicCommAddr:
geographicAddr:
telecomAddr:
effectiveStartDate: DATETIME
effectiveEndDate: DATETIME
+
+
+
+
+
has a
BRIDG Shared Classes::
1..* RoleRoleRelationship
1
+ source:
+ type: CodedConcept
+ target:
has a
1
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::Participant
Clinical Research
Entities and Roles::
HealthCareSite
+ studySubjectIdentifier: int
+ arm: string
+ subgroupCode: string
+ informedConsentFormSignedDate: date
+ offStudyDate: date
+ studyAgentDoseLevel: string
+ eligibilityWaiverReason: string
+ ageAtEnrollment: int
::Participation
+ type: CodedConcept
+ status: CodedConcept
0..1 + statusDate: DATETIME
+ startDate: DATETIME
+ endDate: DATETIME
+source 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
relationshipCode: PSMCodedConcept
Obsolete_relationQualifier: BRIDGCodedConcept
sequenceNumber: NUMBER
pauseCriterion:
checkpointCode:
priorityNumber: NUMBER
splitCode:
negationRule: AbstractRule
joinCode:
negationIndicator: BOOLEAN
conjunctionCode:
Clinical Trials Activities::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 Activities::PlannedActivity
::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 Activities::PerformedActivity
0..*
1
+ 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 Activities::
StudySite
+ targetAccrualNumber: int
::Participation
+ type: CodedConcept
+ status: CodedConcept
+ statusDate: DATETIME
+ startDate: DATETIME
+ endDate: DATETIME
1
+
* +
*
+
+
+
+
+
+
+
+target activity
0..*
0..*
Protocol Concepts::StudyDocument
+
+
+
+
+
+
+
+
+
Clinical Trials Activities::
StudyAgent
Clinical Research
Entities and Roles::
AgentRole
Clinical Research Entities and
Roles::Agent
0..*
1
Clinical Research
Entities and Roles::
FundingSponsor
Clinical Research Entities and
Roles::OrganizationRole
id: CodedConcept
name: string
description: string
status: CodedConcept
statusDate: DATETIME
geographicAddr: addrType
telecomAddr: TEL
+
+
+
+
+
+
+
+
1
+ paymentMethod: CodedConcept
+ confidentialityCode: string
Clinical Trials Activities::SubjectAssignment
+ signatureCode: int
+ signatureText: string
0..*
::Participation
+ type: CodedConcept
+ status: CodedConcept
+ statusDate: DATETIME
+ startDate: DATETIME
+ endDate: DATETIME
+ certificateLicenseText:
Clinical Research Entities
and Roles::Organization
+
+
+
+
+
+
+
Clinical Trials Activities::
StudyInvestigator
Clinical Research
Entities and Roles::
Investigator
Clinical Research Entities and Roles::
PersonRole
::Role
+ id: CodedConcept
+ code: CodedConcept
+ status:
+ electronicCommAddr:
+ geographicAddr:
+ telecomAddr:
+ effectiveStartDate: DATETIME
+ effectiveEndDate: DATETIME
+
+
+
+
+
+
+
+
+
+
+
+
+
1..*
Clinical Research Entities and Roles::Person
+
+
+
+
+
+
+
+
+
+
+
+
+
BRIDG Shared Classes::
ActivityActivityRelationship
BRIDG Shared Classes::Activity
type: CodedConcept
status: CodedConcept
statusDate: DATETIME
startDate: DATETIME
endDate: DATETIME
Clinical Research
Entities and Roles::
TherapeuticAgent
id: CodedConcept
name: string
description: string
status: CodedConcept
formCode: CodedConcept
lotNumber: int
expirationDate: DATETIME
stabilityTime: DATETIME
::Participation
+ type: CodedConcept
+ status: CodedConcept
+ statusDate: DATETIME
0..* + startDate: DATETIME
+ endDate: DATETIME
1
1
1
Clinical Trials
Activities::
ObservationRelationship
Clinical Trials
Activities::
AssessmentRelationship
+ id: int
- type: string
+ comments: string
+ id: int
+ typeCode: string
+ commentText: string
Clinical Trials Activities::
PerformedStudy
+ id: BRIDGID
1 + longTitle: string
1 + shortTitle: string
+ phaseCode: ENUM
+ intentCode: ENUM
+ monitorCode: ENUM
+ blindedInd: boolean
+ randomizedInd: boolean
+ diseaseCode: CodedConceptDataType
+ sponsorCode: CodedConceptDataType
+ multiInstitutionInd: boolean
+ targetAccrualNumber: int
0..*
1
version: string
author: SET
ID: SET BRIDGID
documentID: BRIDGID
type: ENUM
description: BRIDGDescription
title: string
status: BRIDGStatus
confidentialityCode: CodedConcept
0..*
0..*
1
1
0..*
+
+
+
+
+
Clinical Trials Activities::Assessment
id: int
reportingDate: date
confidentialityCode: string
uncertaintyCode: string
statusCode: string
+ id: int
+ evaluationDate: date
1..*
0..*
0..*
1
BRIDG Shared Classes::BRIDGAnalysisVariable
+
+
+
+
name: TEXT
value:
controlledName: PSMCodedConcept
businessProcessMode: PSMBusinessProcessMode
BRIDG Shared Classes::
BRIDGCodedConcept
-
code: TEXT
codeSystem:
codeSystemName: TEXT
codeSystemVersion: NUMBER
displayName: TEXT
originalText: TEXT
translation: SET{PSMCodedConcept}
BRIDG Shared Classes::BRIDGDescription
+ synopsis: EncapsulatedData
+ summaryDescription: EncapsulatedData
+ detailedDescription: EncapsulatedData
BRIDG Shared Classes::
BRIDGBusinessProcessMode
+ modeValue: ENUM {Plan, Execute}
BRIDG Shared Classes::
BRIDGContactAddr
BRIDG Shared Classes:
:BRIDGInterval
+ type: BRIDGCodedConcept
+ effectiveTime: BRIDGInterval
+ usage: BRIDGCodedConcept
- startTime: timestamp
+ endTime: timestamp
BRIDG Shared
Classes::
BRIDGID
+ source: Text
+ version: Text
+ value: Text
BRIDG Shared Classes::
BRIDGStatus
+ effectiveEndDate:
+ effectiveStartDate:
+ statusValue:
«abstraction»
Clinical Trials Activities::AdverseEvent
Clinical Trials Activities::Histopathology
0..*
+
+
+
+
0..* +
+
0..*
1
1
Clinical Trials Activities::Observation
+ grossExamResultCode: string
+ reportDescriptiveText: string
+ involvedSurgicalMarginIndicator: boolean
Clinical Trials Activities::
SubstanceAdministration
doseQuantity: int
doseUnitOfMeasure: string
route: string
doseFrequency: string
doseModificationType: string
doseChangeType: int
1
0..*
1
Clinical Trials Activities::
HistopathologyGrade
Clinical Trials Activities::Procedure
+ targetSiteCode: string
+
+
+
+
id: int
gradingSystemName: string
grade: string
comments: string
0..*
Clinical Trials Activities::
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 Activities::
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
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
1..*
Clinical Trials
Activities::
Neoplasm
Clinical Trials
Activities::
Surgery
Clinical Trials
Activities::
SpecimenCollection
+ siteCondition: string
+ method: string
+specimenCollection
Clinical Trials Activities::
Radiation
+ therapyType: string
+ doseUnitOfMeasure: string
+ dose: string
identifier: string
contrastAgentEnhancement: string
descriptiveText: string
rateOfEnhancementValue: int
+ id: int
+ submissionDate: date
+ filedIndicator: boolean
Clinical Trials Activities::DiseaseResponse
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
+
+
+
+
+
+
+
+
+
+
responseCode: char
responseCodeSystem: string
bestResponseCode: char
bestResponseDate: date
progressionDate: date
progressionPeriod: int
progressionPeriodUnitOfMeasureCode: string
doseChangeIndicatorCode: int
courseDispositionCode: string
commentText: string
1
0..1
Clinical Trials Activities::
CancerStage
+
+
+
+
+
Clinical Trials
Activities::
AdverseEventReport
+ id: int
+ cellType: string
Clinical Trials Activities::Diagnosis
+
+
+
+
+
+
+
+
+
+
+
+
+
1
0..1
Clinical Trials Activities::Imaging
+
+
+
+
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
id: int
tnmStage: string
tnmStageCodeSystem: string
stageCode: string
stageCodeSystem: string
Clinical Trials Activities::
DeathSummary
+ deathDate: date
+ deathCauseCode: char
+ deathCauseText: string
+ autopsiedIndicator: boolean
1
Clinical Trials Activities::
QualitativeEvaluation
1
0..*
1..*
+specimenCollection 0..*
Clinical Trials Activities:
:Specimen
+ id: int
+ idNumber: int
+ samplingType: string
Clinical Trials Activities::
AdverseEventTherapy
+
+
+
+
+
id: int
treatmentDate: date
delayDuration: int
delayDurationUnitOfMeasureCode: string
intensityCode: string
Clinical Trials Activities::
MetastasisSite
+ id: int
+ anatomicSiteCode: string
+ anatomicSiteCodeName: string
Clinical Trials
Activities::
LesionEvaluation
+ evaluationCode: char
+
+
+
+
+
+
+
+
survivalStatusCode: int
survivalStatusDescriptionText: string
performanceStatusCode: int
performanceStatusCodeSystem: string
painIndexCode: int
painIndexCodeSystem: string
anamResultAccuracyPercent: int
menstrualPatternTypeCode: string
menstrualIndicator: boolean
FDA IT Plan (CDISC-HL7 Message)
Site
Sponsor
CDISC Content and Interchange
Interchange:
HL7 output file
CDISC Content
Trial Design
CDASH
FDA Reviewers
Data Checker
and Loader
Sponsor
Data
Warehouse
(ODM)
Site Data
Archive
(ODM)
MedWatch AE
Reports (ICSR)
SDTM
ADaM
Janus
FDA/NCI
Analytical Data
Warehouse
Review
Tools