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© CDISC 2015
The CFAST Approach: Developing TA Standards Efficiently and Collaboratively Rhonda Facile, BA, MS Vice President, Standards Development
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© CDISC 2015
Agenda • CDISC • The CFAST Initiative • TA Development Process • CDISC SHARE • FDA Specifications • TA User Guide Orientation • Year 3 – Lessons learned • How to get involved • CDISC Fellows Program
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© CDISC 2015
Acknowledgements
Thanks to Wayne Kubick, Rebecca Kush, Diane Wold and Rachael Zirkle for their contributions to
this presentation.
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© CDISC 2015
CDISC has established worldwide industry standards to support the electronic acquisition, exchange, submission and archiving of clinical research data and metadata to improve data quality and streamline medical and biopharmaceutical product development and research processes
Consensus-based development
Standards are freely available at www.cdisc.org
IP Policy ensures open standards
© CDISC 2014
Members, Supporters, Volunteers, Stakeholders,
Adopters
CDISC Operations
CDISC User Networks
CDISC Teams
CDISC Coordinating Committees
CDISC Board of Directors
CDISC
CDISC Advisory Council
© CDISC 2015
Disclaimer…
CDISC Standards Do Not specify what data should be collected or how to conduct
clinical trial protocols, assessments or endpoints.
CDISC Standards specify how to structure the data to support efficient data sharing for
regulated clinical trials
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© CDISC 2014 8
It’s about Patients!
© CDISC 2015
CFAST is an initiative of CDISC and the Critical Path Institute to accelerate clinical research and medical product development by facilitating the creation and maintenance of data standards, tools, and methods for conducting research
in therapeutic areas important to public health.
© CDISC 2014
Collaborations & Governance
CFAST TAPSC Therapeutic Area Program
Steering Committee
CFAST SAC Scientific Advisory Committee
• Prioritizes/Approves Proposals • Approves Projects & Charters • Resources & Oversees Projects
• Provides Scientific Advice to TAPSC • Identifies Risks and Opportunities • Identifies/Engages Relevant Partners
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© CDISC 2015
Project Organization & Roles
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Project Manager
TA Clinical Experts
TA Statistics Experts
Metadata Developers
CDISC Team Representatives
Program Manager
Technical Writers
Modeling Expert
Terminology/QRS Experts
CDASH Team
SDS Team
ADaM Team
Terminology/QRS Teams
Review Community
CDISC, C-Path, FDA, PMDA, Transcelerate BioPharma, Inc., Key Opinion Leaders, Medical Associations, U.S. National Institutes of Health, Innovative Medicines Initiative, others
CFAST Governance
Medical Writer
CDISC Standards Review Council
CFAST TA Steering Committee
(TAPSC)
CFAST Scientific Advisory Committee
(SAC)
CDISC Governance
Collaboration and Feedback
© CDISC 2015
CFAST Program • Launched in 2012 by partners CDISC and C-Path • SAC initiated in 2013 • Asthma Pilot completed November 2013 included:
Enhanced development process* Introduced new roles* TA User Guide content & layout* Concept modeling using concept maps* Metadata displays* SDTM
• Goal is to expand content to developing concept level “Beginning to End” Biomedical Concepts
(* new aspects)
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© CDISC 2015
Working Principles • Focus on Core concepts that apply to all phases
of clinical trials in a specific TA Minimal Valuable Product (MVP) for 1st versions
• Minimize text, where possible Focus on explaining concept maps, metadata and
examples
• Use SHARE eco-system tools, where possible As tools become available, use them to develop concept
metadata
• Reuse content to assemble TA packages
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© CDISC 2015
Published Standards
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http://www.cdisc.org/therapeutic
Standards Available for Download!
© CDISC 2015
Therapeutic Area Project
Project Manager
Stage 0 Charter
Approval
Stage 1 Check of Concepts
Completed
Stage 3a Posted
for Internal Review
Stage 3b Posted
for Public Review
Stage 3c Projected Standards Publicatio
n
Notes
Traumatic Brain Injury v1 Amy Palmer Oct 13 Sep 14 Mar Jul Q415 SRC Review for Pub: Nov 2
Breast Cancer v1 John Owen Oct 14 Oct 14 Mar Nov Q116 PR: Nov
COPD v1 Sherwood Barbee Sep 14 Dec 14 Jul Nov Q415 PR: Nov 4 – Dec7
ADaM Supp to Diabetes v1 Rachael Zirkle NA NA Mar Jul Q415 SRC Review for Pub: Nov 23
Diabetic Kidney Disease v1 Rachael Zirkle May Aug Nov Jan 16 Q116
Tuberculosis v2 Laura Butte Apr Apr Sep Oct Q116 PR: Oct 28 – Nov 30
Rheumatoid Arthritis v1 Trisha Simpson Jun Oct Dec Jan 16 Q216
CV Imaging v1 Amy Palmer May Jul Nov Jan 16 Q216 SRC Review for PR: Nov 23
Prostate Cancer v1 John Owen Nov Q316
MDD v1 Amy Palmer Nov Q316
GAD v1 Amy Palmer Triple-Scope Q316
Bi-polar Disease v1 Amy Palmer Triple-Scope Q316
Solid Organ (Kidney) Transplant Laura Butte Jan 16 Q316
Key| Stage completed | Stage ongoing | All months reflect when stage is, or is projected to be, completed. November 3, 2015
Program Overview – November 2015
Stage 0 – Scoping , Stage 1 – Concept Modeling, Stage 2 – Standards Development, Stage 3a – Internal Review, Stage 3b – Public Review, Stage 3c – Publication
Upcoming Publications 4Q15/1Q16: • Traumatic Brain Injury (Just Published!) • Diabetes ADaM Supplement • COPD • Breast Cancer • Diabetic Kidney Disease • Tuberculosis v2
© CDISC 2015
CFAST Pipeline
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http://www.cdisc.org/system/files/all/CFAST_ProjectPipeline.pdf
© CDISC 2015
CDISC TA Standards Development Process
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© CDISC 2014 18
Set scope Enough to be useful Not too much to achieve in 10-12 months Identify regulatory and clinical guidelines Involve clinicians Start with system-independent concept maps Where does the data come from? What are the data items and what do they mean? How are the data items related?
Process for developing content Stage 1 Scoping
Develop “biomedical concept” metadata Based on the BRIDG model to provide underlying
consistency Includes CDASH and SDTM metadata Includes controlled terminology values and subsets of
values Develop implementation examples Create TA User Guide Modules CDISC review process “Internal” cross-team review Public Review
Process for developing content Stage 2 Concept Modeling
Stage 3 Develop
Standards
Stage 3a Internal Review
Stage 3b Public Review
The first CDISC TA standard (TB, 2012) was a supplement to the SDTMIG Organized by SDTM domain No mention of any other standard CFAST TA projects expanded to other standards Asthma: SDTM, prototype biomedical concept
metadata Diabetes: added CDASH examples QT Studies: included ADaM examples Schizophrenia: includes trial design examples
Beginning to End Coverage
© CDISC 2015
Growing Content
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TAUG Components
Terminology SDTM CDASH ADaM
Piloted ADaM supplement coming Q4 CDASH, ADaM - TBD
Some CDASH under consideration
Biomedical concept metadata: a small package of relevant variables and terminology for a particular research concept (e.g., a particular test) CDASH prompt/question text SDTM domain, test/test code Applicable variables Computational method, if applicable (e.g., BMI) Subset of relevant controlled terminology
To be curated in SHARE metadata repository
Adding depth
© CDISC 2015
CDISC SHARE
© CDISC 2015
SHARE
BRIDG, ISO21090
Protocol, CDASH
SDTM, ADaM
Terminologies
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• Single, trusted, authoritative source for CDISC data standards
• Concepts, metadata, collections, relationships, value sets across the full spectrum of CDISC content
• Links research to healthcare concepts to support interoperability
• Aligned with NCI Semantic Systems
• Access to data standards
• Source to target mapping & traceability
• Transformation logic
Facilitates Data
Exchange
c. Impact Analysis & Inheritance
b. Gov’c work-flows
a. Change control
c b
a
Adapted from Source by Sue Dubman, Sanofi-Aventis
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SHARE is CDISC’s metadata repository along with supporting tools The first priority for SHARE was loading existing standards CDISC development teams are benefitting from SHARE Consistency checking, version comparisons Cataloging domains, supplemental qualifiers,
examples Will be the repository for biomedical concept metadata
SHARE
Concrete, machine readable “value level” metadata Implementation use cases: Building protocol schedule of events Automating CRF creation Automating database creation Automating tabulation (SDTM) creation Tabulation validation Metadata-driven analysis
Biomedical Concept Metadata
Today Extrapolate for data not
in implementation guides
Connect up separate standards
Figure out how to pull together the right structural and terminology elements
Future Standards cover more
content TA user guides and
biomedical concept metadata integrate across standards
Download machine-readable, immediately useable standards
Impact on implementers
© CDISC 2015
SHARE Video
http://www.youtube.com/watch?v=gCyVdvgVpY8&feature=youtu.be
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© CDISC 2015
FDA TA Standards Acceptance Project
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© CDISC 2015
TA Standards Specification for FDA & User Guides Modularized Content
Normative • TA User Guides
For data managers, programmers, others..
Includes: • Implementation instructions • Concept maps and
explanations • Examples
– SDTM, Controlled Terminology and other standards
• Appendices – Glossary – Known issues – References – Team list – IP policy
Non-Normative • TA Specifications
For the FDA data standards catalogue
Includes: • New domains/variables
specifications – Domain tables – New variables
»Standard and Non-Standard
• SDTM Rules • Controlled Terminology • Known issues • Evolve to Biomedical
Concept Metadata tables – over time
© CDISC 2015
FDA TA Standards Acceptance Project
Source: draft dyslipidemia Spec
© CDISC 2015
FDA TA Standards Acceptance Project
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Source: draft dyslipidemia spec
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FDA TA Standards Acceptance Project • Initial Implementation plan – Published TA
Standards Dyslipidemia – by EOY QT Studies Hepatitis C Virus Diabetes TBv2
• Ongoing projects Plan under development
• BrCa to be ready at the publication of the TA User Guide
© CDISC 2015
CDISC’s Evolving Culture of Learning
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© CDISC 2015
CDISC’s Culture of Learning
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Assessment & Feedback
Group Interaction
Coaching
Forums
Best Practices
Technology
• Assessment & Feedback Lessons Learned Does it work/not work? Make needed changes
• Group Interaction Use of dialogue & skillful discussion to
draw out group intelligence that is greater than the sum of individual member’s talent.
• Coaching Modeling Expert CDISC Experts, SRC, etc.
• Forums Concept Modeling Metadata Development
• Best Practices Process documentation Tools, Checklists, etc
• Leverage Technology CDISC SHARE
(Adapted from Peter Senge, The Dance of Change: The Challenges of Sustaining Momentum in Learning Organizations, Doubleday, New York, 1999)
© CDISC 2015
• TA Clinical Expert – Consultative role. A therapeutic area expert who checks accuracy of modeling, via concept maps and CRF modules.
• *Metadata Developer – person who interacts with TA Clinical Expert, draws concept maps, populates concept template for individual concepts, requests new terminology and prepares examples
• *Metadata Curator – person who loads metadata into and extracts metadata from SHARE. Checks new concept templates and maps
• Modeling Expert – Consultative role. Person who creates and/or checks new concept templates.
• SHARE Programmer – person who writes programs to turn concept template diagrams into concept metadata tables. May also create/improve tools ( e.g. CRF generator and SDTM generator).
*roles merge over time?
NEW ROLES
© CDISC 2015
Metadata Tools Team – Purpose • Ensure Metadata Developer training is available
and comprehensive • Ensure additional resources, (e.g., examples and
templates for concept maps, metadata spreadsheets, and SDTM examples) are easily accessible
• Ensure clearly defined processes are available and accessible
• Provide support for Concept Mapping Forum and Metadata Development Forum
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© CDISC 2015
Metadata Developers’ Forum
• Purpose: To provide a forum for presenting and discussing SDTM modeling issues that arise during TA development. Feedback at the earliest stage of data modeling (reduces rework of
examples) Provides modeling support at all levels of review (Internal, SRC, Public) Consistent modeling across TAUGs
• Areas Covered: TAs: Hep C, Schizophrenia, TBI, TB, Virology, COPD Topics: Challenges of using the physiology domains, deciding when to
use FA, terminology issues surrounding PRTRT and SUTRT
• When: twice weekly
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Concept Modelers’ Forum
• Purpose: To teach concept modeling approaches & support development teams
• Areas Covered: All TA projects, as needed. Foundational team projects are
also welcome. Topics: Representing research
concepts and their metadata visually, mapping domain models, learning to use the tool
• When: Meets twice weekly, as needed
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© CDISC 2015
Toolkits for TA and Foundational Teams
Therapeutic Area Standards 1. Standards Development Guideline 2. Standards Development Process Map 3. Scoping Checklist 4. Pharma Survey Template 5. Concept Listing Spreadsheet 6. Gap Analysis Template 7. Steps for Searching Clinicaltrials.gov 8. Therapeutic Area User Guide Template 9. SHARE RC Metadata Template 10.Concept Modeling – recorded training 11.Concept Modeling Checklist 12.Metadata Developer Resources 13. Internal Review Checklist 14.Public Review Checklist 15.Publication Checklist 16.Project Close-out Checklist
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Foundational Standards 1. Standards Development Guideline 2. Standards Development Process Map 3. Internal Review Checklist 4. Public Review Checklist 5. Publication Checklist
TA & Foundational 1. Project Proposal Template 2. Project Charter Template 3. Project Plan Template 4. Lessons Learned Template 5. Communications Process Table 6. Review Stages Summary 7. CDISC Style Guide 8. SRC QC Checklist 9. SRC Transmittal Form 10. Instructions on using the
Internal/Public Comment Tracker 11.Comment Resolution Instructions 12.CDASH Tool kit 13.Development of Concepts &
Metadata (Training Module)
Location: TA Process Documents
Common Process Documents Wiki
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Oncology Development Plan
© CDISC 2015
TA User Guide - Orientation
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TA User Guide Contents -
• Introduction • A list of patient directed resources on the
Indication • SDTM domains • SDTM Metadata Examples
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Example SDTM metadata
© CDISC 2015
TA User Guide Contents – Concept Maps • Illustrates relationships among concepts and attributes
• Facilitates understanding (semantic interoperability) among functions involved in standards development
Self-Monitoring Blood Glucose (SMBG) – example
Diagram 2: Self-Monitoring Blood Glucose Glucose measurements typically performed by subjects with diabetes are indicated. The glucose meter device requires a whole blood sample, but the glucose reading may be read as either a whole blood equivalent or a plasma equivalent.
© CDISC 2015
TA User Guide Contents -
CDASH Annotated CRF example – Hypoglycemia
© CDISC 2015
Example CDASH (CRF) Metadata Table - Hypoglycemia
© CDISC 2015
CDISC SHARE Metadata Example – CM and Treatment Naïve
Shows BRIDG
basis and detailed values
© CDISC 2015
Year 3 – Lessons Learned
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© CDISC 2015
Lessons Learned
• TA standards development will drive/are driving development of most CDISC standards
• Attention to project scope is essential • Point to reference material, don’t repeat it • Smaller, experienced resourced teams
Focused clinical input Large review community input at Internal and Public
Review
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Where we are going • Streamlining & Modularizing TA User Guides
focus on “Core” information
• Use Pre-populated templates, where possible • Produce Normative Specifications for all TA User
Guides for FDA • Update Published TA User Guides (point versions)
to remove draft domains Create an area on the wiki where those draft SDTM
domains and other proposed changes can be maintained.
• Extract examples from older TA User Guides and loading them into SHARE.
• Continually observe what works & what doesn’t
© CDISC 2015
How to get Involved • Join a TA working group • Comment on draft standard at the Internal
Review and/or Public Review • Attend the Interchange • Participate in the CDISC Fellow program
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© CDISC 2015
CDISC Fellows Program CDISC Fellows: • Actively participate in the development of CDISC standards
on a near full-time basis for a fixed period of time (nominally one year)
• Develop proficiency in the development, use and maintenance of standards
• Acquire knowledge that can be leveraged internally by sponsoring companies
• Provide ongoing part-time expertise as a reviewer or other participant to the CDISC collaboration
community
http://www.cdisc.org/cdisc-fellows-program
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© CDISC 2015
CDISC Fellows Class of 2015-2016
• Mikenlette Avent, UCB • Cliff Reinhardt, UCB • Dany Guerendo, STATProg Inc. • Kapila Patel, InventiveHealth • Dr. Helen Sile, FDA* • Sharon Powell, Independent* • Sandeep Savant, InventiveHealth* • Junchao Chen, Shanghai University of TCM* • Anayansi Van Der Berg, RA eClinical Solutions* • Ruiling Peng, Beijing Improve-Quality
Technology Ltd. Co. • Phillip Ho, Rundo Int Pharmaceutical Research &
Development Co. • Qingna (Joy) Li, Xiyuan, Hospital, China
Academy of Chinese Medical Sciences *not pictured
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© CDISC 2014
CDISC – Beginning to End (quality, speed, provenance)
Protocol
SDTM
Analysis ADaM
Data Capture
ODM
Database
ODM
CDASH eCRFs
