CDISC MDR Definitions & examples on concepts & variables December 2008.

CDISC MDR

Definitions & examples on concepts & variables

December 2008

- 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


Table of Content

• What is CMDR – architecture & definition

• Examples

• Open questions


What is CMDR– Value proposition

– Architecture

– Definitions


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.


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


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

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What is CMDR: definitionsInformation Model Layer

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Data Type Layer

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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..*

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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..*

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1..*1

1..*1

0..1

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1..*1

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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

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What is CMDR: definitionsData type Layer

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Data Type Layer

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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

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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


What is CMDR: definitionsData Layer

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Data Type Layer

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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


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

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Examples of simple concepts and related variables

– One simple concept, one variable

– One simple concept, several variables


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



Valid ValuesFemale C246Male C1323Unknown C2691 ……




C1913



C42614


(ConceptualDomain.ObjectClass.Property.Representation.Values)

Info

rmat

ion

Mo

del

BR

IDG


Example within ISO11179 (1 simple concept = 1 variable, concept fully defined in BRIDG)




Valid Values…….??????Object Class

PersonC1892

Propertyname

C42614

Conceptual DomainPerson Name

C1913

Value DomainPerson


C42614


(ConceptualDomain.ObjectClass.Property.Repsentation.Values)

Info

rmat

ion

Mo

del

BR

IDG


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…


Need to specify content o

f the diffe

rent boxes



Valid ValuesFemale C246Male C1323Unknown C2691 …… C1818




C1913



C42614



Info

rmat

ion

Mo

del

BR

IDG


What is CMDR: example within 11179 (1 simple concept = 1 variable, concept defined generically in BRIDG)

PerformedObservationResult.name


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)


f the diffe

rent boxes



Valid ValuesFemale C246Male C1323Unknown C2691 …… C1818




C1913



C42614



Info

rmat

ion

Mo

del

BR

IDG


What is CMDR: example within 11179 (1 simple concept = many variables, concept defined generically in BRIDG)

PerformedClinicalObservationResult.

numericResult



f the diffe

rent boxes


Examples of complex concept within “ontology”

– Inclusion/exclusion criteria

– Procedures

– Combination of procedures around disease

– eCRF Forms

– Standard Data Sets (STDM, ADaM, …)


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


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 ???


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 ???


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


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


Complex concepts: procedureHPV treatment - Step 1 – Disease detection


Other concept


role(s)

• HPV detection • Plasma• Collection


• HPV Amplicor Test


date/time

• Demographics• Disease history• Treatment history

Mandatory

Optional


Complex concepts: procedureHPV treatment - Step 2 – Disease classification/treatment selection



role(s)

• HPV disease classification / treatment selection

• Plasma• Collection


• HPV LR Test• Result value• Result unit• Measurement

date/time

Mandatory

Optional


Complex concepts: procedureHPV treatment - Step 3 – Treatment

CRF Study design Concept


role(s)

• Disease Treatment by therapeutic vaccination

Mandatory

Optional

Other concept

• Weight measurement


Complex concepts: procedureHPV treatment - Step 4 – Disease monitoring



role(s)

• Disease monitoring

• Plasma• Collection


• HPV Amplicor test


date/time

Mandatory

Optional


Open questions– ….


• 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 ?


• 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…)

CDISC MDR Definitions & examples on concepts & variables December 2008.

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Transcript of CDISC MDR Definitions & examples on concepts & variables December 2008.