PRACTICAL END-TO-END METADATA FOR CLINICAL STUDY DATA…portal.cdisc.org/CDISC User Networks/Europe/English... · – Road to the future, build metadata today that will set us up

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

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© 2012 Actelion Pharmaceuticals Ltd

The eClinical project at Actelion

Status

Metadata approach

Practical work to date

AGENDA

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© 2012 Actelion Pharmaceuticals Ltd3


THE ECLINICAL PROGRAMME

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STEP-WISE (ITERATIVE) APPROACH

CLINICAL DATA STANDARDIZATION

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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 …)

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33

44

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EDC(CDASH)EDC(CDASH)11


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

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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


THE PRINCIPLE: DEFINE ONCE, USE MANY

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THE REALITY: ARCHITECTURE

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Generic Metadata (CDISC & Actelion Standards)

StudyConfiguration

EDC (Rave)

SDTM


THE REALITY: THE “MDR”

MDR

AGE

yyy

zzz

Protocol

eCRF & EDC Raw DataSet

CDASH

Age

Units

TabulationsComponent

ActelionTerminology

CDISCTerminology SDTM

Code Lists


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”

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COMPONENTS

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Generic Metadata(CDISC & Actelion

Standards)


COMPONENTS

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Standards)

Grouping of single variables into useful concepts for re-use.

This level – logical collection of variables – is animportant one


COMPONENTS

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Standards)

Optionality


COMPONENTS

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Standards)

Pre-setting of variablesfor when SDTM created


COMPONENTS

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Standards)

Some further levels ofgrouping needed


COMPONENTS

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Standards)

Use of new CDISCQuestionnaireterminology


TABULATIONS

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Standards)


TABULATIONS

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Standards)

Split controlled terms andformats and added fixed

value


COMPONENT “VIEWS”

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Validation

Com

ponent(s)


Standards)

Annotated CRF

ODM (XML)

Automated


COMPONENT “VIEWS”

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Validation

Com

ponent(s)


Standards)

Annotated CRF

ODM (XML)


STUDY DEFINITIONS

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StudyConfiguration

Com

ponent(s)

StudyBuild


SDTM GENERATION

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SDTM

Generic Metadata

RaveClinicalView(s)

SDTMDomain

SAS Programs. Sequence of simple operations. Not all steps mayrequired metadata

Study & SDTM Configuration


SDTM GENERATION

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SDTM


ONE CLICK

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SDTM


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

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3

4

Analysis Datasets


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


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


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

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3

4

Analysis Datasets

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MDR INTEGRATION WITH THE BUSINESS

MDR

Protocol Writing

Study Build

DataCapture

Tabulations

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3

4

Analysis Datasets

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= A utility thattakes the

metadata within theMDR and translates itinto a format suitablefor the business toolsto perform the desiredbusiness function


LESSONS – METADATA NEEDS TO BE …

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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


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

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STANDARDS, WHO NEEDS THEM?

© CDISC 2012

Presented byDave Iberson-HurstAssero Ltd

Commentary byDiane WoldGSK

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Producing Usable Therapeutic AreaStandards

Documents

PRACTICAL END-TO-END METADATA FOR CLINICAL STUDY DATA…portal.cdisc.org/CDISC User Networks/Europe/English... · – Road to the future, build metadata today that will set us up