standards metadata management (system)

© COPYRIGHT 2015 MARKLOGIC CORPORATION. ALL RIGHTS RESERVED.

Standards Metadata Management (System)Kevin Lee, MarkLogic

© COPYRIGHT 2015 MARKLOGIC CORPORATION. ALL RIGHTS RESERVED. SLIDE: 2

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


Standards?

What do we think first about Standards?


Standards based electronic submission of clinical trial data


Current Status in eSubmission in CDER FDACurrent Status in eCTD Standards Submission in CDER FDA


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


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.


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


New FDA Guidance on CDISC eSubmission - continued

Can FDA “Refuse to File / Receive” if submission data does not follow eStudy Guidance?

YES


What else for Standards?

• Anything else beside submission?• What else can we do with standards?


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


Standards based

submission

Standards driven

process


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)


Model T production and price over year

1909

1910

1911

1912

1913

1914

1915

1916

1917

1918

1919

1920

1920

1921

1922

1923

1924

1925

1926

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

$0 $100 $200 $300 $400 $500 $600 $700 $800 $900 $1,000

ProductionPrice for

1910: $900 and 20,000 vs 1925: $260 and 2,000,000


Can we accomplish similar production increases and cost reduction in clinical artefacts development like Henry Ford did?


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


Standards driven clinical artefacts development

ETL system

Standards SDTM ADaM

Clinical Artefacts

SDTM datasets ADaM datasets


Questions

What are required for standards-driven clinical artefacts development?


Requirements for standards-driven automated clinical artefacts development

Standards Metadata

Management System

ETL Systems


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)


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


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


• Types of Standards metadata• Protocol (e.g.,PRM)• CDASH• SEND• SDTM• ADaM• Define.xml• Dataset.xml• Any company specific Standards

Standards Metadata Management - continued


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


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


What does it mean by Standards metadata driven process?

• Standards metadata first or Standards data first?

• Create metadata first or data first?


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


Evolution of metadata system

Spreadsheet or document

Database

Metadata Management System


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)


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


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;


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


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


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


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


Semantics-driven Study level metadata definition development in MdM : Oncology

Protocol

Cheson 2007

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


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


Final Thought

Management

Standards MetadataStandards

Regulatory Clinical Data Submission

Standards Metadata-driven Clinical

Artefacts Development


Contacts and Questions Kevin LeeEmail: [email protected] LinkedIn: www.linkedin.com/in/HelloKevinLee

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standards metadata management (system)

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