A metadriven approach for
definition and management of
clinical standards within a CDW
repository environment, current
challenges and visions for
improvements
iCDW
PhUSE SDE
Copenhagen 15 Mar 2010
Mikkel Traun
[email protected]
iCDW
Outline
CDW Operations
The Standards in CDW
Metadata in CDW
Clinical Standards Ontology
Clinical System Architecture
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 2
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 3
CDW Operations
Development and
support of the
Clinical Data
Warehouse system
Development and
maintenance of
Use of System
components
How are we
organised?
• Metadata entry &
mapping application
• Controlled terminology
• Part of Clinical Systems
& Data Management in
Global Development
• Data model
• Statistical computing
environment
• Mapping of data from
CDMS to the Clinical
Data Warehouse
• Standard programs
• Data enrichment
• Statistical output
• Twenty employees
• Standard Supporters,
Programmers and
Specialists within these
areas
iCDW
The Standards in CDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 4
- ensuring reusability, traceability and consistency
CRF
CRF
CRF
Date:
Protocol
Standards
CRF
Standards
Submission
Standard
/ /
Abc
:
x:
y:
Qwr:
CDISC SDTM
ADaM
Data Domain: CDISC
PE
<XML>
.…
Standard
DCM/DVGs
Planned Finding
Planned Categoric Response Subset
Subject
OC
Table
PLANNED EVENT GROUP: NORMAL LABEL
PLANNED EVENT SUB GROUP: NORMAL LABEL
CDW
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
PROFILE TYPE: CODE
PLANNED INTERVENTION GROUP: NORMAL LABEL
PLANNED INTERVENTION SUB GROUP: NORMAL LABEL
Planned Finding Method
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE: CODE
RANGE START DATE: DATE
LAB_ID: NUMBER
Planned Profile Time Collection
RANGE STOP DATE: DATE
NORMAL RANGE TYPE.RANGE TYPE: CODE
CLINICAL SIGNIFICANCE RANGE TYPE.RANGE TYPE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
FINDING TOPIC CODE: CODE
Planned Finding Normal Range
Planned Profile Time Point
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
Planned Profile Dosing
Visits
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
GENERIC ELEMENT SEQUENCE NUMBER: SORT SEQUENCE
COMPOUND SEQUENCE NUMBER: SORT SEQUENCE
Planned Clinical Significance Range
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE.TOPIC CODE: CODE
RANGE START DATE: DATE
COUNTRY: CODE
SEX.CATEGORIC RESPONSE VALUE CODE: CODE
LOWER AGE: NUMBER
UPPER AGE: NUMBER
LAB_ID: NUMBER
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE: CODE
RANGE START DATE: DATE
COUNTRY: CODE
SEX.CATEGORIC RESPONSE VALUE CODE: CODE
LOWER AGE: NUMBER
UPPER AGE: NUMBER
LAB_ID: NUMBER
AGE UNIT.TIME UNIT: CODE
LOWER RANGE: NUMBER
UPPER RANGE: NUMBER
RANGE UNIT.UNIT: CODE
AGE UNIT.TIME UNIT: CODE
LOWER RANGE: NUMBER
UPPER RANGE: NUMBER
RANGE UNIT.UNIT: CODE
Numeric Findings
TIME POINT SEQUENCE: SORT SEQUENCE
NOMINAL TIME: NUMBER
SEQUENCE TIME: CODE
SCHEDULED TIME: DATETIME
SCHEDULED DAY: NUM ID
Responses
Categoric Findings
Events
XXCgfg hghj dklædfjkll sdfkf jklsd
(AE/Hypo/x)
----------------------------------Xxxx
Interventions
Elements
Table
Standard
Mappings
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
INTERVENTION TOPIC CODE.TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
EVENT TOPIC CODE.TOPIC CODE: CODE
PLANNED FINDING GROUP: NORMAL LABEL
PLANNED FINDING SUB GROUP: NORMAL LABEL
PROFILE NAME: NORMAL LABEL
LOWER LIMIT TYPE: CODE
LOWER LIMIT VALUE: NUMBER
LOWER LIMIT RULE: CODE
LOWER LIMIT VALUE CENSORED: FLAG
LOWER LIMIT UNIT.UNIT: CODE
Planned Profile
Std. EOT
Planned Intervention Registration
Planned Event Registration
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE.TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
CATEGORIC RESPONSE LIST: CODE
CATEGORIC RESPONSE VALUE CODE: CODE
FINDING TOPIC CODE.TOPIC CODE: CODE
Mapping
rules
Data Domain: ADPE
<XML>
.…
Standard
Code Values
Standard
Reports
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iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Benefits of using metadata
• See previous presentations:
• Standardisation of Trial Design Definitions in CDW at Novo
Nordisk
• Mikkel Traun, Novo Nordisk, CDISC User Group 2008
• Data Standardisation, Clinical Data Warehouse and SAS®
Standard Programs
• Jean-Marc Ferran, Novo Nordisk, PhUSE Manchester 2008
• Managing your metadata efficiently
• Kirsten Langendorf, Novo Nordisk, PhUSE Basel 2009
• Metadata and Standard Programs
• Marianne Carames & Martin Lindhard, Novo Nordisk, PhUSE
Basel 2009
Slide no 5
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 6
Standards, Controlled Terminology and
General Clinical Metadata in CDW
• Standards – Structure and content
• These are specific areas where you have
agreed upon a standard: Protocol, CRF and
Report/Business Rules standards
Std. EOT
XXCgfg hghj dklædfjkll sdfkf jklsd
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• Controlled Terminology – Input & Output Content
• Codes, labels and the content definition
• Clinical Metadata – CDW implementation
• How Standards and Controlled Terminology is
implemented in CDW
Planned Finding
Planned Categoric Response Subset
Planned Intervention Registration
Planned Event Registration
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
INTERVENTION TOPIC CODE.TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE.TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
EVENT TOPIC CODE.TOPIC CODE: CODE
PLANNED FINDING GROUP: NORMAL LABEL
PLANNED FINDING SUB GROUP: NORMAL LABEL
PROFILE NAME: NORMAL LABEL
LOWER LIMIT TYPE: CODE
LOWER LIMIT VALUE: NUMBER
LOWER LIMIT RULE: CODE
LOWER LIMIT VALUE CENSORED: FLAG
LOWER LIMIT UNIT.UNIT: CODE
PLANNED EVENT GROUP: NORMAL LABEL
PLANNED EVENT SUB GROUP: NORMAL LABEL
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
CATEGORIC RESPONSE LIST: CODE
CATEGORIC RESPONSE VALUE CODE: CODE
FINDING TOPIC CODE.TOPIC CODE: CODE
Planned Profile
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
PROFILE TYPE: CODE
PLANNED INTERVENTION GROUP: NORMAL LABEL
PLANNED INTERVENTION SUB GROUP: NORMAL LABEL
Planned Finding Method
Planned Profile Time Collection
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
FINDING TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE: CODE
RANGE START DATE: DATE
LAB_ID: NUMBER
RANGE STOP DATE: DATE
NORMAL RANGE TYPE.RANGE TYPE: CODE
CLINICAL SIGNIFICANCE RANGE TYPE.RANGE TYPE: CODE
Planned Finding Normal Range
Planned Profile Time Point
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
TIME POINT SEQUENCE: SORT SEQUENCE
NOMINAL TIME: NUMBER
SEQUENCE TIME: CODE
SCHEDULED TIME: DATETIME
SCHEDULED DAY: NUM ID
Planned Profile Dosing
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
GENERIC ELEMENT SEQUENCE NUMBER: SORT SEQUENCE
COMPOUND SEQUENCE NUMBER: SORT SEQUENCE
Planned Clinical Significance Range
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE.TOPIC CODE: CODE
RANGE START DATE: DATE
COUNTRY: CODE
SEX.CATEGORIC RESPONSE VALUE CODE: CODE
LOWER AGE: NUMBER
UPPER AGE: NUMBER
LAB_ID: NUMBER
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE: CODE
RANGE START DATE: DATE
COUNTRY: CODE
SEX.CATEGORIC RESPONSE VALUE CODE: CODE
LOWER AGE: NUMBER
UPPER AGE: NUMBER
LAB_ID: NUMBER
AGE UNIT.TIME UNIT: CODE
LOWER RANGE: NUMBER
UPPER RANGE: NUMBER
RANGE UNIT.UNIT: CODE
AGE UNIT.TIME UNIT: CODE
LOWER RANGE: NUMBER
UPPER RANGE: NUMBER
RANGE UNIT.UNIT: CODE
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 7
Challenges when using metadata
• Complex dependencies and prerequisites between:
•
•
•
•
•
•
•
•
•
•
•
•
Standard Table Shells
Input parameters for Standard Reporting Programs
Standard Reporting Programs
Derived Variable and Enrichment Framework
Statistical Programming Specifications
Defined Trial Metadata
Source Data Mappings
Source Data Collections
eCRF
Protocol Metadata Document
Protocol Metadata Template
Defined General Clinical Metadata and Controlled Terminology
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
The Standards in the Reporting & Data Flow
Slide no 8
- ensuring reusability, traceability and consistency
CRF
CRF
CRF
Date:
Protocol
Standards
CRF
Standards
Submission
Standard
/ /
Abc
:
x:
y:
Qwr:
CDISC SDTM
ADaM
Data Domain: CDISC
PE
<XML>
.…
Standard
DCM/DVGs
Planned Finding
Planned Categoric Response Subset
Subject
OC
Table
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
INTERVENTION TOPIC CODE.TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
EVENT TOPIC CODE.TOPIC CODE: CODE
PLANNED FINDING GROUP: NORMAL LABEL
PLANNED FINDING SUB GROUP: NORMAL LABEL
PROFILE NAME: NORMAL LABEL
LOWER LIMIT TYPE: CODE
LOWER LIMIT VALUE: NUMBER
LOWER LIMIT RULE: CODE
LOWER LIMIT VALUE CENSORED: FLAG
LOWER LIMIT UNIT.UNIT: CODE
PLANNED EVENT GROUP: NORMAL LABEL
PLANNED EVENT SUB GROUP: NORMAL LABEL
Planned Profile
CDW
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
PROFILE TYPE: CODE
PLANNED INTERVENTION GROUP: NORMAL LABEL
PLANNED INTERVENTION SUB GROUP: NORMAL LABEL
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE: CODE
RANGE START DATE: DATE
LAB_ID: NUMBER
RANGE STOP DATE: DATE
NORMAL RANGE TYPE.RANGE TYPE: CODE
CLINICAL SIGNIFICANCE RANGE TYPE.RANGE TYPE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
FINDING TOPIC CODE: CODE
Planned Profile Dosing
Visits
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
PROFILE NAME: NORMAL LABEL
TIME POINT: NUM ID
GENERIC ELEMENT SEQUENCE NUMBER: SORT SEQUENCE
COMPOUND SEQUENCE NUMBER: SORT SEQUENCE
Planned Clinical Significance Range
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE.TOPIC CODE: CODE
RANGE START DATE: DATE
COUNTRY: CODE
SEX.CATEGORIC RESPONSE VALUE CODE: CODE
LOWER AGE: NUMBER
UPPER AGE: NUMBER
LAB_ID: NUMBER
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE: CODE
RANGE START DATE: DATE
COUNTRY: CODE
SEX.CATEGORIC RESPONSE VALUE CODE: CODE
LOWER AGE: NUMBER
UPPER AGE: NUMBER
LAB_ID: NUMBER
AGE UNIT.TIME UNIT: CODE
LOWER RANGE: NUMBER
UPPER RANGE: NUMBER
RANGE UNIT.UNIT: CODE
AGE UNIT.TIME UNIT: CODE
LOWER RANGE: NUMBER
UPPER RANGE: NUMBER
RANGE UNIT.UNIT: CODE
Numeric Findings
TIME POINT SEQUENCE: SORT SEQUENCE
NOMINAL TIME: NUMBER
SEQUENCE TIME: CODE
SCHEDULED TIME: DATETIME
SCHEDULED DAY: NUM ID
Std. EOT
Planned Finding Method
Planned Profile Time Collection
Planned Finding Normal Range
Planned Profile Time Point
Responses
Categoric Findings
Events
(AE/Hypo/x)
XXCgfg hghj dklædfjkll sdfkf jklsd
Interventions
Mapping
rules
Standard
Code Values
----------------------------------Xxxx
Elements
Table
Standard
Mappings
Planned Intervention Registration
Planned Event Registration
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
FINDING TOPIC CODE.TOPIC CODE: CODE
TRIAL ID: TRIAL ID
TRIAL DEFINITION ID: CHAR ID
TRIAL METADATA VERSION: NUM ID
CATEGORIC RESPONSE LIST: CODE
CATEGORIC RESPONSE VALUE CODE: CODE
FINDING TOPIC CODE.TOPIC CODE: CODE
Data Domain: ADPE
<XML>
.…
Standard
Reports
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iCDW
PhUSE SDE Copenhagen 15 Mar 2010
What Is An Ontology
• An ontology is an explicit description of a
domain:
•
•
•
•
concepts
properties and attributes of concepts
constraints on properties and attributes
Individuals (instances)
• An ontology defines
• a common vocabulary
• a shared understanding
Slide no 9
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 10
Ontology - From Wikipedia
In computer science and information science, an ontology is a
formal representation of the knowledge by a set of concepts within
a domain and the relationships between those concepts. It is used
to reason about the properties of that domain, and may be used to
describe the domain.
In theory, an ontology is a "formal, explicit specification of a
shared conceptualisation".[1] An ontology provides a shared
vocabulary, which can be used to model a domain — that is, the
type of objects and/or concepts that exist, and their properties and
relations.[2]
Ontologies are used in artificial intelligence, the Semantic Web,
systems engineering, software engineering, biomedical
informatics, library science, enterprise bookmarking, and
information architecture as a form of knowledge representation
about the world or some part of it. The creation of domain
ontologies is also fundamental to the definition and use of an
enterprise architecture framework.
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 11
Clinical Standards Ontology
• Domain model of clinical standards and their end-toend relationship and dependencies
• Not an implemented system model
• Why develop an ontology of clinical standards?
• To share common understanding of the structure of
clinical information among people and systems
• A Clinical Standards Ontology can:
•
•
•
•
•
Support requirement specifications
Support program development and testing
Improve documentation
Improve user guidance and support
Improve system maintenance
Ontology tool - Protégé
iCDW
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 13
An ontology driven clinical architecture
• When you have a mature and stable ontology model of
all relationships and dependencies in the clinical
standards and data flow in the clinical development
process
• Then make a clinical system architecture that utilise
this model in a shared master data repository
• iCDW
iCDW
iCDW
• How is your vision of an iCDW?
PhUSE SDE Copenhagen 15 Mar 2010
Slide no 14