cdisc mdr definitions & examples on concepts & variables december 2008
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- 2 -CDISC Meta Data Repository – November 2008
Foreword
All examples taken in this presentation are extracted from BRIDG 1.1.
For the purpose of the presentation, the release is not important.
But while looking a the examples must take into account that there might be differences with the last release of
BRIDG
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Table of Content
• What is CMDR – architecture & definition
• Examples
• Open questions
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What is CMDR– Value proposition
– Architecture
– Definitions
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What is CMDR: value proposition
The CDISC Meta Data Repository (CMDR) is a “cross industry enriched data dictionary”, supporting full
semantic interoperability.
It will allow cost avoidance in each pharma companies (decrease cost for standards maintenance and data mapping) while improving data quality, critical for
effective scientific decision making.
In addition it will enable new capabilities required by authorities – such as comparative profile for safety and
cost-efficacy – and will support EHR integration.
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What is CMDR: content
• CMDR is composed by concepts and variables
– Concepts are • Abstract ideas associated to a representation i.e. a variable• Related to each others in an information model/ontology (based on BRIDG and on
HL7/ISO abstract data type)Note: BRIDG fully bound to controlled terminologies for all the attributes specified as CD can be considered – at least partially – as an ontology for clinical research
• Unambiguous as their semantic is fully defined • Used and defined at scientific level (generally in protocol)
– Variables • are linked to concepts and • are used to collect, derived and store all information related to a concept in a computer • Note: variables can be considered as the equivalent of what company currently have
in terms of data dictionary
• CMDR content must be controlled through strict Governance
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What is CMDR: architecture
CDISC MDR
Information Model Layer (BRIDG)
Data Layer (concepts & variables)
Data Type Layer
Scientific View(clinical &
non-clinical concept)
Data Manager & Biostat view
(variables)
Data Integrator view
Terminologies
code
Terms(meaning)
code
Terms(meaning)
code
Terms(meaning)
LOINC
SNOMED
MEDDRA
CDISC Vocab
Sponsor OwnMDRSponsor Own
MDRSponsor/CRO
Regulators / HealthCare Own MDR
SEND
CDASH
ADaM
SDTM
Governance
CDISC MDR
- 8 -CDISC Meta Data Repository – November 2008
What is CMDR: definitionsInformation Model Layer
CDISC MDR
Information Model Layer (BRIDG)
Data Layer (concepts & variables)
Data Type Layer
CDISC MDR
An information model is composed by objects, further described by properties and relationship with other objects. Properties have an abstract data type.
class my v iews
PerformedActivity
PerformedObserv ation
+ name: CD+ targetSite: CD+ method: CD+ bodyPosition: CD::PerformedActivity+ actualDateRange: IVL<TS>+ actualDuration: PQ+ effectiveDateRange: IVL<TS>+ effectiveDuration: PQ+ missedIndicator: BL+ missedReason: SET<SC>::Activity- identifier: II+ category: CD+ subcategory: CD+ codedDescription: CD+ textDescription: ST+ reason: SET<CD>+ status: CD+ statusDateRange: IVL<TS>+ comment: ST
PerformedObserv ationResult
ObservationResult
PerformedClinicalResult
+ codedResultModifiedText: ST+ numericPrecision: INT+ referenceTextList: CD+ referenceRangeLow: REAL+ referenceRangeHigh: REAL+ referenceRangeComment: ST+ reportedResultStatus: CD+ asCollectedIndicator: BL+ normalRangeComparison: CD::ObservationResult+ reportedDate: TS+ codedResult: CD+ numericResult: PQ+ textResult: ST+ targetSite: CD+ confidentiality: CD+ uncertainty: CD+ baselineIndicator: BL+ comment: ST
1
0..*
CDISC MDR
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What is CMDR: definitionsInformation Model Layer - BRIDG
class BRIDG
Document
StudyProtocol
PlannedStudy
Activity ObservationResult
PerformedActivity
ScheduledActivity
PerformedStudy
PlannedActivity PlannedObservationResult
PerformedObservationResult
PerformedObservation
StudySubject
StudyAgent
PlannedArmPlannedStudyCell
PlannedEpoch
PlannedStudySegment
Participant Person
TherapeuticAgent
ManufacturedMaterial
Material
PerformedSubstanceAdministration
1..*0..1
0..*
0..1
0..*
1
1..*1
1..*1
0..1
0..*
1 0..*
1
0..*
1..*
1
0..1
0..*
0..*1
1..*
1
1..*0..1
1..*1
1..*
0..1
**
0..* 1 10..*
1
0..*1
0..1
0..*
0..1
Concepts are totally defined (e.g SubjectId) => direct linking to variables
Concepts are defined generically (e.g. PerformedObservationResult)=> need to specify each “instance” of concept => indirect linking to variable
CDISC MDR
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What is CMDR: definitionsData type Layer
CDISC MDR
Information Model Layer (BRIDG)
Data Layer (concepts & variables)
Data Type Layer
CDISC MDR
ISO/HL7 abstract data types are data type definitions for representing and exchanging basic concepts that are commonly encountered in healthcare.
Data types used in BRIDG
CDISC MDR
Symbol
Description
CD A concept descriptor represents any kind of concept usually by giving a code defined in a code system. Attributes: code, codeSystem, codeSystemName, codeSystemVersion, displayName, originalText, translation, qualifier)
PQ A dimensioned quantity expressing the result of measuring. Attributes: value, precision , accuracy , unit, translation
II An identifier that uniquely identifies a thing or object. Attributes: root, extension, identifierName, displayable, scope: IdentifierScope
TS A quantity specifying a point on the axis of natural time. YYYY-MM-DDThh:mm:ss.sTZD (eg 1997-07-16T19:20:30.45+01:00)where: TZD = time zone designator (Z or +hh:mm or -hh:mm)
IVL<TS>
IVL is a set of consecutive values of an ordered base datatype. Attributes: low , lowClosed, lowUnbounded, high, highClosed, highUnbounded , width
PN A restriction of EN used when the named Entity is a Person. Attributes: part : A sequence of name parts, such as given name or family name, prefix, suffix, etc, use
AD Mailing and home or office addresses. Attributes part : A sequence of address parts, such as street or post office Box, city, postal code, country, etc, use, useablePeriod, isNotOrdered
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What is CMDR: definitionsData Layer
CDISC MDR
Information Model Layer (BRIDG)
Data Layer (concepts & variables)
Data Type Layer
CDISC MDR
The data layer is composed by concepts and their associated variables
Concept can be complex or simple• a complex concept is composed by other concepts
(complex or simple) through a structured organizational framework or ontology – i.e. the information model with controlled terminology
• VS contains Weight, Height, systolic blood pressure…• Blood pressure: 2 possibilities
• Standing systolic blood pressure upper arm contains systolic blood pressure, position = standing, site = upper arm
• Systolic Blood pressure with conditional concepts & variable such as position and site
• a simple concept may be related to many different complex concepts and must be linked to all variables capturing the meaning related to the concept
• Systolic blood pressure is linked to SYS_BP_val, SYS_BP_unit, SYS_BP_precision
• Person Gender is linked to Person_Gender
CDISC MDR
Semantic of concepts must be unique and captured in structured way, following ISO11179
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What is CMDR: definitionsData Layer
Observation •Name: CD•Position: CD•Site: CD•Value: any•Time: TS
PQ = integer, unit, range
CD = code list, source, ….
ID1_SYSBP •Name = SYSBP•Position: restricted CD from observation•Site: restricted CD from observation•Value: PQ•Time: TS
SYSBPLOCSYSBPSITESYSBPVAL, SYSBPU
ID2_TMP •Name = TMP•Position: restricted CD from observation•Site: restricted CD from observation•Value: PQ
SYSBPLOCSYSBPSITESYSBPVAL, SYSBPU SYSBPTimeofMesurement
TMPLOCTMPSITETMPVAL, TMPU
In caDSR = Observation.name.SYSBP.position.list of restricted CD
In caDSR = Observation.name.SYSBP.site.list of restricted CD
In caDSR = Observation.name.SYSBP
In caDSR = different representation (integer & mmHG, real& cmHG)
Qualifier = VS domain (explicit context) When qualifier is VS, then synonym of position = VSPOS and site = VSLOCVSPOS and VSLOC would point to “SYSBPLOC and TMPLOC”…. Based of the VSTestname value
TS = ….
Info
rmat
ion
L
ayer
Dat
a L
ayer
Dat
a T
ype
Lay
er
CDISC MDR
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Examples of simple concepts and related variables
– One simple concept, one variable
– One simple concept, several variables
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Data Element ConceptPerson.gender
Valid ValuesFemale C246Male C1323Unknown C2691 ……
Object ClassPersonC1892
PropertygenderC42614
Conceptual DomainGENDER
C1913
Value DomainGENDER value
RepresentationGender code
C42614
Data Element (= CONCEPT in sense of CMDR): Person.Gender Data type: CDSemantic Signature: C1913.C1892.C42614.C42614.C246.C1323….
(ConceptualDomain.ObjectClass.Property.Representation.Values)
Info
rmat
ion
Mo
del
BR
IDG
VARIABLE: personGenderData type: CD
Example within ISO11179 (1 simple concept = 1 variable, concept fully defined in BRIDG)
Code lists F, Female ,C246M. Male, C1323U, Unknown, C2691 ……
There is a black box behind this (s
ee next slide).
CDISC MDR data standard stewards need to
understand it in details.
End users are not interested
- 15 -CDISC Meta Data Repository – November 2008
Data Element ConceptPerson.gender
Valid ValuesFemale C246Male C1323Unknown C2691 ……
Object ClassPersonC1892
PropertygenderC42614
Conceptual DomainGENDER
C1913
Value DomainGENDER value
RepresentationGender code
C42614
Data Element (= CONCEPT in sense of CMDR): Person.Gender Data type: CDSemantic Signature: C1913.C1892.C42614.C42614.C246.C1323….
(ConceptualDomain.ObjectClass.Property.Representation.Values)
Info
rmat
ion
Mo
del
BR
IDG
VARIABLE: personGenderData type: CD
Example within ISO11179 (1 simple concept = 1 variable, concept fully defined in BRIDG)
Code lists F, Female ,C246M. Male, C1323U, Unknown, C2691 ……
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Data Element ConceptPerson.gender
Valid Values…….??????Object Class
PersonC1892
Propertyname
C42614
Conceptual DomainPerson Name
C1913
Value DomainPerson
RepresentationGender code
C42614
Data Element (= CONCEPT in sense of CMDR): Person.Gender Data type: CDSemantic Signature: C1913.C1892.C42614.C42614.C246.C1323….
(ConceptualDomain.ObjectClass.Property.Repsentation.Values)
Info
rmat
ion
Mo
del
BR
IDG
VARIABLE: personGenderData type: CD
What is CMDR: example within 11179 (1 simple concept = many variables, concept fully defined in BRIDG)
QUESTIONS
What is the conceptual domain for data type PN ???
For for type PQ ???
Can we establish a formal relationship between a ADT and the related variables,
based on the ITS of the datatype ? For instance PQ always associated with 4
variables: value, unit, range, precision…
Code lists F, Female ,C246M. Male, C1323U, Unknown, C2691 ……
Need to specify content o
f the diffe
rent boxes
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Data Element ConceptPerson.gender
Valid ValuesFemale C246Male C1323Unknown C2691 …… C1818
Object ClassPersonC1892
PropertygenderC42614
Conceptual DomainGENDER
C1913
Value DomainGENDER value
RepresentationGender code
C42614
Data Element (= CONCEPT in sense of CMDR): Person.Gender Data type: CDSemantic Signature: C1913.C1892.C42614.C42614.C246.C1323….
(ConceptualDomain.ObjectClass.Property.Repsentation.Values)
Info
rmat
ion
Mo
del
BR
IDG
VARIABLE: personGenderData type: CD
What is CMDR: example within 11179 (1 simple concept = 1 variable, concept defined generically in BRIDG)
PerformedObservationResult.name
Code lists F, Female ,C246M. Male, C1323U, Unknown, C2691 ……
QUESTIONS
How do we link a Generic object like PerformedObservation result with a specific concept –e.g. systolic blood
pressure
How/where do we link all code value that are contrained toegther (e.g. Bodyposition for Sys BP has only a limited set of value)=> do we need to create a fully instantiated
version of BRIDG (for all PerfomedObservationResults – which would constitute the concepts – out of
which we can then create the variables ???/
(this can be stored in ISO11170 but should be displayed in a user friendly way – with
graphics
If we do this – we also need to create some kind of structure (e.g. BP is subspecialized
in SYSBP and DIAS BP)
Need to specify content o
f the diffe
rent boxes
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Data Element ConceptPerson.gender
Valid ValuesFemale C246Male C1323Unknown C2691 …… C1818
Object ClassPersonC1892
PropertygenderC42614
Conceptual DomainGENDER
C1913
Value DomainGENDER value
RepresentationGender code
C42614
Data Element (= CONCEPT in sense of CMDR): Person.Gender Data type: CDSemantic Signature: C1913.C1892.C42614.C42614.C246.C1323….
(ConceptualDomain.ObjectClass.Property.Repsentation.Values)
Info
rmat
ion
Mo
del
BR
IDG
VARIABLE: personGenderData type: CD
What is CMDR: example within 11179 (1 simple concept = many variables, concept defined generically in BRIDG)
PerformedClinicalObservationResult.
numericResult
Code lists F, Female ,C246M. Male, C1323U, Unknown, C2691 ……
Need to specify content o
f the diffe
rent boxes
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Examples of complex concept within “ontology”
– Inclusion/exclusion criteria
– Procedures
– Combination of procedures around disease
– eCRF Forms
– Standard Data Sets (STDM, ADaM, …)
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Complex concepts
• Complex concepts are composed by simple or complex concepts. The same simple concept – with potentially a different code list or value – can be used for different concepts
• So far the following complex concepts that would be valuable to standardize across the industry have been identified
– Inclusion/exclusion criteria
– Procedures
– Combination of procedures around disease
– SDTM domains
– eCRF Forms
– Standard Analysis Data Sets
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Complex concept: inclusion/exclusion criteria
• Most inclusion/exclusion criteria would be a simple concept such as
– Age < or > a certain value
– Tumor size < or > a certain value
– Note: the actual criteria will be a combination of the concept/variable with a specific value (e.g. age below 20 years) …..CMDR provides the definition of the concept/variable (e.g. age), the data integrator provides the value (e.g. below 20 years)
• Some inclusion/exclusion criteria – including several check – are complex concept
– ???? Example ???
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Concept: Depression
HAMD ItemsHAMD-DTotalScore
Variables• HAMD Total Score• AETERM: “Depressed/Depression/Depressive Symptoms”• TRT+IFU: “Antidepressant for Depression”• BPRS Item 9
BPRS ItemsBRPSTotalScore
Concept: Positive,Negative,
or Affective Symptoms of Psychotic Disorder
Variables• BPRS Total Score
Concept: Anxiety
Variables• BAI Total Score• HAMD-D Item 11• AETERM: “Anxious/Anxiety/Panic”• TRT+IFU: “Anxiolytic for Anxiety”• BPRS Item 2
BAI ItemsBAITotalScore
EQ5D Question 5
“Are you Anxious or Depressed?”
Complex concept: Forms ???
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Complex concepts: procedureConcept interdependencies: concept with testing
CRF Study design Concept Sample Finding
Other concept
• CRF template(s) • Visit(s)• Data collector
role(s)
• Variable(s) with permissible values
• Sample type(s)• Collection
date/time• Volume/Weight• Quality• Storage condition• Location
• Result value• Result unit• Measurement
date/time
• Simple or complex concept
Mandatory
Optional
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Complex concepts: procedureConcept interdependencies: HPV treatment
Treat DiseaseTreat
Disease
HPVTherapeutic
Vaccine
Detect Disease Detect Disease
HPVAmplicor
Monitor Response Monitor
Response
HPVAmplicor
Select Treatment
Select Treatment
HPVLinear Array
• HPV causes cervical cancer
• Cervical cancer is2nd biggest cause
of female cancermortality
• Up to 250,000 deaths / year
Human papilloma virus
Source: WHO
- 25 -CDISC Meta Data Repository – November 2008
Complex concepts: procedureHPV treatment - Step 1 – Disease detection
CRF Study design Concept Sample Finding
Other concept
• CRF template(s) • Visit(s)• Data collector
role(s)
• HPV detection • Plasma• Collection
date/time• Volume/Weight• Quality• Storage condition• Location
• HPV Amplicor Test
• Result value• Result unit• Measurement
date/time
• Demographics• Disease history• Treatment history
Mandatory
Optional
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Complex concepts: procedureHPV treatment - Step 2 – Disease classification/treatment selection
CRF Study design Concept Sample Finding
• CRF template(s) • Visit(s)• Data collector
role(s)
• HPV disease classification / treatment selection
• Plasma• Collection
date/time• Volume/Weight• Quality• Storage condition• Location
• HPV LR Test• Result value• Result unit• Measurement
date/time
Mandatory
Optional
- 27 -CDISC Meta Data Repository – November 2008
Complex concepts: procedureHPV treatment - Step 3 – Treatment
CRF Study design Concept
• CRF template(s) • Visit(s)• Data collector
role(s)
• Disease Treatment by therapeutic vaccination
Mandatory
Optional
Other concept
• Weight measurement
- 28 -CDISC Meta Data Repository – November 2008
Complex concepts: procedureHPV treatment - Step 4 – Disease monitoring
CRF Study design Concept Sample Finding
• CRF template(s) • Visit(s)• Data collector
role(s)
• Disease monitoring
• Plasma• Collection
date/time• Volume/Weight• Quality• Storage condition• Location
• HPV Amplicor test
• Result value• Result unit• Measurement
date/time
Mandatory
Optional
- 30 -CDISC Meta Data Repository – November 2008
• Around Time related variable
– SDTM is having one variable for data+time
– CDASH is decomposing this in 2 or more variable
– Should we have the variables defined only at the most granular level – related to a hierarchy of concepts
– Or should we have as well a hierarchy of variable
– What is the +/- of both ?
- 31 -CDISC Meta Data Repository – November 2008
• Systolic blood pressure – and “concept code list”
– What is the conceptual domain for the concept systolic blood pressure – is this the Data type (i.e. PQ) ?
– concept = systolic blood pressure – which is a PQ (physical quantity). A PQ is implemented through a value, unit, range, precision • related variables are hence SYSBP_VAL, SYSBP_unit, SYSBP_range,
SYSBP_precision; • this does not include position and location which are part of a “complex concept”
called “clinical measurement” including indeed position, site but also devices, ….
– Measurement unit and systolic blood pressure• the "concept" measurement unit is related to a very long list of code • for systolic blood pressure we want only a subset of this. I believe this is where the
"implementation" of BRIDG comes into place i.e. we will specify for each possible measurement like systolic blood pressure and all ... exactly which value applies.... though we need to show how this will practically work !!!
– How to represent the different concept (SYS_BP standing UA, SYS_BP_supine…)