Post on 12-May-2020
Copyright © 2012 Actelion Pharmaceuticals Ltd
PRACTICAL END-TO-END METADATA FORCLINICAL STUDY DATA: A CASE STUDY
Dave Iberson-Hurst, Assero LimitedEnglish Speaking User Group, London 15th November 2012
1
© 2012 Actelion Pharmaceuticals Ltd
The eClinical project at Actelion
Status
Metadata approach
Practical work to date
AGENDA
2
© 2012 Actelion Pharmaceuticals Ltd3
© 2012 Actelion Pharmaceuticals Ltd
THE ECLINICAL PROGRAMME
4
© 2012 Actelion Pharmaceuticals Ltd
STEP-WISE (ITERATIVE) APPROACH
CLINICAL DATA STANDARDIZATION
5
1. EDC(CDASH)
2. Data Tabulations(SDTM)
3. Analysis Datasets(ADaM)
5. Regulatory Submission
4. Protocol
Data Tabs(SDTM)Data Tabs(SDTM)
Analysis Datasets(ADaM)Analysis Datasets(ADaM)
Machine readable protocol(PR)Machine readable protocol(PR)
Regulatory submission(eCTD, SDTM, ADaM …)Regulatory submission(eCTD, SDTM, ADaM …)
22
33
44
55
EDC(CDASH)EDC(CDASH)11
© 2012 Actelion Pharmaceuticals Ltd
Four EDC trials live– And Two Studies
• Configured based on standard metadata (definitions)• SDTM created from data captured within EDC using an
automated tool based on metadata (definitions)
Two New Studies– Following the above described design & implementation
Governance– Structure and governance group in place– Standards metadata (definitions) being reviewed and approved
WHERE WE ARE TODAY
6
© 2012 Actelion Pharmaceuticals Ltd
Assist the team managing the definitions (metadata) in increasing theamount of standardized content available for study configuration
Mature the governance process around the definitions
Investigate methods by which the protocol and EDC setup can be bettercoordinated
AE and SAE information: make sure we work with the same definitions
Work with Biostats in the use of SDTM and ADaM in their work
The provision of a meta data repository (MDR) to meet the above needs
NEXT STEPS FOR 2012
CLINICAL DATA STANDARDIZATION
© 2012 Actelion Pharmaceuticals Ltd
THE PRINCIPLE: DEFINE ONCE, USE MANY
8
© 2012 Actelion Pharmaceuticals Ltd
THE REALITY: ARCHITECTURE
9
Generic Metadata (CDISC & Actelion Standards)
StudyConfiguration
EDC (Rave)
SDTM
© 2012 Actelion Pharmaceuticals Ltd
THE REALITY: THE “MDR”
MDR
AGE
yyy
zzz
Protocol
eCRF & EDC Raw DataSet
CDASH
Age
Units
TabulationsComponent
ActelionTerminology
CDISCTerminology SDTM
Code Lists
© 2012 Actelion Pharmaceuticals Ltd
Simple Pragmatic Approach
– Uses Excel– Human Readable & Machine Readable– Road to the future, build metadata today that will set us up for
tomorrow• New Draft FDA guidance talks of metadata & relationships• Therapeutic Area Development• SHARE
Blending SDTM & CDASH & Terminology into re-usable “components”
Culture change
– People not technology– Training
THE “MDR”
11
© 2012 Actelion Pharmaceuticals Ltd
COMPONENTS
12
Generic Metadata(CDISC & Actelion
Standards)
© 2012 Actelion Pharmaceuticals Ltd
COMPONENTS
13
Generic Metadata(CDISC & Actelion
Standards)
Grouping of single variables into useful concepts for re-use.
This level – logical collection of variables – is animportant one
© 2012 Actelion Pharmaceuticals Ltd
COMPONENTS
14
Generic Metadata(CDISC & Actelion
Standards)
Optionality
© 2012 Actelion Pharmaceuticals Ltd
COMPONENTS
15
Generic Metadata(CDISC & Actelion
Standards)
Pre-setting of variablesfor when SDTM created
© 2012 Actelion Pharmaceuticals Ltd
COMPONENTS
16
Generic Metadata(CDISC & Actelion
Standards)
Some further levels ofgrouping needed
© 2012 Actelion Pharmaceuticals Ltd
COMPONENTS
17
Generic Metadata(CDISC & Actelion
Standards)
Use of new CDISCQuestionnaireterminology
© 2012 Actelion Pharmaceuticals Ltd
TABULATIONS
18
Generic Metadata(CDISC & Actelion
Standards)
© 2012 Actelion Pharmaceuticals Ltd
TABULATIONS
19
Generic Metadata(CDISC & Actelion
Standards)
Split controlled terms andformats and added fixed
value
© 2012 Actelion Pharmaceuticals Ltd
COMPONENT “VIEWS”
20
Validation
Com
ponent(s)
Generic Metadata(CDISC & Actelion
Standards)
Annotated CRF
ODM (XML)
Automated
© 2012 Actelion Pharmaceuticals Ltd
COMPONENT “VIEWS”
21
Validation
Com
ponent(s)
Generic Metadata(CDISC & Actelion
Standards)
Annotated CRF
ODM (XML)
© 2012 Actelion Pharmaceuticals Ltd
STUDY DEFINITIONS
22
StudyConfiguration
Com
ponent(s)
StudyBuild
© 2012 Actelion Pharmaceuticals Ltd
SDTM GENERATION
23
SDTM
Generic Metadata
RaveClinicalView(s)
SDTMDomain
SAS Programs. Sequence of simple operations. Not all steps mayrequired metadata
Study & SDTM Configuration
© 2012 Actelion Pharmaceuticals Ltd
SDTM GENERATION
24
SDTM
© 2012 Actelion Pharmaceuticals Ltd
ONE CLICK
25
SDTM
© 2012 Actelion Pharmaceuticals Ltd
MDR KEY USE CASES
MDR
Protocol Writing
Study Build
DataCapture
Tabulations
1. -
2. Use metadata to build thestudy
3. Load the study build intothe data capture systems
4. Use metadata to take theraw data and build SDTM
5. -
6. -
StandardsTeam createand manage
the metadatadefinitions
2
3
4
Analysis Datasets
© 2012 Actelion Pharmaceuticals Ltd
THE NEXT STEP
aaa
yyy
zzz
Units
CRF Componentsand links to SDTM
Code Lists
SDTM DomainDefinitions
StudySpecificSDTM
DefinitionSDTM Driver
TLG Driver
ActelioneCRFS
SDTMStandard
The above havebeen used to drivethe design ofmetadata for SDTMcreation
ADaMStandard &
ActelionAnalysis
DefinitionsActelionTLGs
Repeat the approach todesign metadata
definitions with currentTLGs and analysis data
as the starting point
ADaM Driver
ADaMDefinitions
SDTMTabulations
Analysis Datasets
TLGs
© 2012 Actelion Pharmaceuticals Ltd
aaa
yyy
zzz
Units
SHARE COMMON DEFINITIONS TO ENABLE TRACEABILITY
SDTM DomainDefinitions
StudySpecificSDTM
DefinitionSDTM Driver
TLG Driver
ADaM Driver
Common Variable Definitions & Code Lists (Controlled Terminology)
Use
d by
Use
d by
ADaMDefinitions
Use
d by
CRF Componentsand links to SDTM
Traceability to CRFaaa
yyy
zzz
Units
SDTMTabulations
Analysis Datasets
TLGs
© 2012 Actelion Pharmaceuticals Ltd
MDR KEY USE CASES
MDR
Protocol Writing
Study Build
DataCapture
Tabulations
1. Use metadata (from theMDR) to assist instructuring relevant dataitems in the protocol (tableof assessments)
2. Use metadata to build thestudy
3. Load the study build intothe data capture systems
4. Use metadata to take theraw data and build SDTM
5. With the associateddefine.xml
6. Generation of further itemsto support the analysisprocess
StandardsTeam createand manage
the metadatadefinitions
12
3
4
Analysis Datasets
65
© 2012 Actelion Pharmaceuticals Ltd
MDR INTEGRATION WITH THE BUSINESS
MDR
Protocol Writing
Study Build
DataCapture
Tabulations
12
3
4
Analysis Datasets
65
= A utility thattakes the
metadata within theMDR and translates itinto a format suitablefor the business toolsto perform the desiredbusiness function
© 2012 Actelion Pharmaceuticals Ltd
LESSONS – METADATA NEEDS TO BE …
31
Well structured
o Layer definitions
Consistent and Complete
Dedicated for a singlepurpose
o Avoid overloading
Reusable
o Define once, use many
o “Concept” – thecollection of variables
Facilitate Automation
o Validation
o Generation of artefacts
o Fit for use by thebusiness
Flexible
o e.g. Code lists
• Subsets
• Hierarchical
• Reuse of items
© 2012 Actelion Pharmaceuticals Ltd
SUMMARY
A lot of metadata built
Applied within four studies using simple tools
SDTM data built using an automated process (90%)
Governance process
Better tools to follow
More studies …
Growing capability …
With the aim to link the Metadata across the lifecycle
32
© 2012 Actelion Pharmaceuticals Ltd
STANDARDS, WHO NEEDS THEM?
© CDISC 2012
Presented byDave Iberson-HurstAssero Ltd
Commentary byDiane WoldGSK
34
Producing Usable Therapeutic AreaStandards