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Standards Metadata Management (System)Kevin Lee, MarkLogic
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AgendaRegulatory Requirement on Clinical Trial Standards(i.e., CDISC and eCTD)
Standards driven clinical artefacts development process
Standards Metadata Management
Metadata Management System
Final Thoughts
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Standards?
What do we think first about Standards?
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Standards based electronic submission of clinical trial data
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Current Status in eSubmission in CDER FDACurrent Status in eCTD Standards Submission in CDER FDA
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Current Status in CDISC Submission in CDER FDA
In 2010, 23% of SDTM in NDA
In 2011, 39% of SDTM and 32% in ADaM in NDA
In 2013, 55% of SDTM in NDA
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Section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act)
• Enhanced by Food and Drug Administration Safety and Innovation Act (FDASIA) on July 9, 2012.
• Requires that submissions be submitted in electronic format.
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New FDA Guidance on CDISC eSubmission
Guidance for Industry: Providing Regulatory Submissions in Electronic Format – Standardized Study Data
Guidance for Industry: Providing Regulatory Submissions in Electronic Format – Submissions Under Section 745A (a) of the Federal Food Drug, and Cosmetic Act
Binding rather than recommendation
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New FDA Guidance on CDISC eSubmission - continued
Can FDA “Refuse to File / Receive” if submission data does not follow eStudy Guidance?
YES
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What else for Standards?
• Anything else beside submission?• What else can we do with standards?
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How does your organization want to use CDISC Standards in the future?
• Regulatory compliance• Reuse of Standards• Operation Efficiency• Faster time to submission• Data interoperabiltiy with other Standards (e.g., HL7)• Data compliance of external vendor• Standards-based or driven clinical trial artefacts development
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Standards based
submission
Standards driven process
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Henry Ford Assembly Line
The Model T was Ford's first automobile mass produced on moving assembly lines with completely interchangeable STANDARDized parts. (Dec 1st, 1913)
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Model T production and price over year
$0 $100 $200 $300 $400 $500 $600 $700 $800 $900 $1,000
0
500,000
1,000,000
1,500,000
2,000,000
2,500,000
ProductionPrice for
1910: $900 and 20,000 vs 1925: $260 and 2,000,000
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Can we accomplish similar production increases and cost reduction in clinical artefacts development like Henry Ford did?
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Henry Ford Assembly line vs Clinical artefacts development process
Henry Ford Car
production
Model T
Interchangeable Standardized
parts
Automated Assembly line
Clinical artefacts
development
SDTM datasets
SDTM & CDASH(EDC), CT standards
Automated ETL system
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Standards driven clinical artefacts development
ETL system
Standards SDTM ADaM
Clinical Artefacts
SDTM datasets ADaM datasets
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Questions
What are required for standards-driven clinical artefacts development?
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Requirements for standards-driven automated clinical artefacts development
StandardsMetadata
Management System
ETL Systems
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Possibility with Standards Metadata Management(MdM) and ETL system
Standards Metadata
Management System
ETL System 1 Clinical Artefacts 1 (Protocol)
ETL System 2 Clinical Artefacts 2 (CDASH/EDC)
ETL System 3 Clinical Artefacts 3 (SDTM)
ETL System 4 Clinical Artefacts 4 (ADaM)
ETL System 5 Clinical Artefacts 5 (TFL)
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Standards Metadata Management• Definition
• Managing Standards Metadata (data about data)• Definition of metadata
• Data about data/document• Title: Star Wars: Episode VII - The Force
Awakens• Release Date: Dec 18th, 2015• Director: J.J. Abrams• Cast: Harrison Ford, Mark Hamill, Carrie
Fisher• Genres: Action, Adventure, Fantasy, Sci-Fi
Metadata
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Standards Metadata Management - continued• Metadata of clinical trial data
• Dataset: DM• Description: Demographics• Class: Special Purpose Domains• Structure: One record per subject• Keys: STUDYID, USUBJID• Versions: SDTMIG 3.2
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• Types of Standards metadata• Protocol (e.g.,PRM)• CDASH• SEND• SDTM• ADaM• Define.xml• Dataset.xml• Any company specific Standards
Standards Metadata Management - continued
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Architetcure of Standards Metadata Management SystemETL System 1 Clinical Artefacts 1
(Protocol)
ETL System 2 Clinical Artefacts 2 (CDASH/EDC)
ETL System 3 Clinical Artefacts 3 (SDTM)
ETL System 4 Clinical Artefacts 4 (ADaM)
ETL System 5 Clinical Artefacts 5 (TFL)
Standards 1 (Protocol)
Standards 2 (CDASH/EDC)
Standards 3 (SDTM)
Standards 4 (ADaM)
Standards 5 (TFL)
Standards Metadata
Management System
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Examples of Standards Metadata Management• Creating new standards (e.g., variables and domains)• Storage of Standards• Modifying the attributes (e.g., label, type) of current standards• Adding the new attributes to current standards• Archiving the standards• Assigning versions (e.g., major or minor) to standards after changes• Maintaining multiple versions of standards (e.g., SDTMIG 3.1.2, 3.1.3)• And many more
• Standards metadata driven process
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What does it mean by Standards metadata driven process?
• Standards metadata first or Standards data first?
• Create metadata first or data first?
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Why Standards metadata first?• Easier to regulatory compliance• Provide requirements / directions to programmers or developers• Don’t need to create metadata(Define.xml) again• Possible standards metadata driven process -> automated process using ETL and MdM
• Standards driven clinical trial artefact development process• How can we do it?• By Metadata System
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Evolution of metadata system
Spreadsheet or document
Database
Metadata Management System
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Metadata Management (MdM) System• Definition• Database created to store metadata
• Function• Storages of Standards metadata in global library• Manage Standards metadata• Govern Standards metadata• Create study level metadata from global library• Receive metadata from other systems (e.g., CDISC SHARE)• Feed metadata to other system(e.g., EDC and ETL system)
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Standards Metadata in MdM system
• Structural metadata of target dataDataset Variable Name Variable Label Type CT RoleDM USUBJID Unique Subject Identifier Char IdentifierDM Age Age Num Identifier
• Structural metadata of source dataDataset Variable Name Variable Label Type CTDEMO USID Unique Subject Identifier Char
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Standards Metadata in MdM system - continued
Target dataset
Target variable
Machine readable derivation Source dataset
Source variable
DM USUBJID = DEMO USIDDM AGE %AGE(RFSTDTC – BRTHDTC)
• System readable transformation metadata from source to target data
data dm;;set demo;;usubjid = usid;;age = %age(rfstdtc – brthdtc);;…
run;;
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Data flow of Standards Metadata in MdM system to ETL and clinical artefacts
ETL System
Source Data
Structural metadata for source
Structural metadata for target
Machine-readable Transformation metadata from source to target
Target Data
Standards Metadata Management System
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Semantics-driven Standards Metadata development
USID
DEMO
hasVariable
USUBJID
DM
hasVariable
AGE
hasVariable
=
Derivation
%age(rdfdtc-brthdtc)
Derivation
require
Rather than row and column structured metadata, developing with semantic based RDF/graph-based smetadata -> PhUSE
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MdM
Protocol
Global Library
CDASH
TFL
ADaM
SDTM
Protocol
Study level (e.g., 001)
CDASH
TFL
ADaM
SDTM
Study level metadata definition development in MdM
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MdM
Protocol
Global Library
CDASH
TFL
ADaM
SDTM
Protocol
Study level (e.g., 001)
CDASH
TFL
ADaM
SDTM
Semantics-driven Study level metadata definition development in MdM
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Semantics-driven Study level metadata definition development in MdM : Oncology
Protocol
Cheson2007
CDASH/EDCTumor
Measurement
SDTM
TR
TFL
Progression Free Survival Time to Event
TFL
ADaM
ADTTEPFS
Bone Marrow Assessment
Spleen and Liver
Enlargement
FA
TU
LB
Response
PE
RS
• Integration from Protocol to Analysis through semantic-linked Standards
• End to End Standardization • System using semantics-driven Standards metadata could automate oncology-specific artifacts developments
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Why is Study Level metadata definition in MdM important?MdM
Protocol
Study 001
CDASH
TFL
ADaM
SDTM
Protocol
EDC database
eCRF
SDTM datasets
ADaM datasets
TFL
ETL
It can dictate study level artefacts development.
Study 001
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Final Thought
ManagementStandards MetadataStandards
Regulatory Clinical Data Submission
Standards Metadata-driven Clinical
Artefacts Development
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Contacts and Questions Kevin LeeEmail: [email protected]: www.linkedin.com/in/HelloKevinLee
Slides: www.slideshare.net/KevinLee56
Tweet: @HelloKevinLee
Blogs: HiKevinLee.tumblr.com