CDASH Initiative

1
CDASH Initiative
CDASH Project Update 6 December 2007 Bay Area
User Group

• Dorothy Dorotheo
• Director, Clinical Data Management
• Intermune, Inc.
• Rhonda Facile
• Director CDASH Project, CDISC

2
CDISC Snapshot

• Global, open, multi-disciplinary non-profit
  organization
• Founded in 1997 incorporated in 2000
• Nearly 200 member organizations
• Biopharmaceutical companies
• Academic Research Institutes
• Technology Vendors, etc
• Active Coordinating Committees
• Europe
• Japan
• Additional activities
• Australia
• India
• S. America and Africa

• Established industry standards to support the
  electronic acquisition, exchange, submission and
  archiving of data to support regulated clinical
  research
• Freely available on the CDISC website
  (www.cdisc.org)
• Developed through open, consensus-based approach

3
CDASH Project Update

• Clinical Data Acquistion Standards Harmonization
• Outline
• Background, Charter and the Collaborative Group
  (RF)
• CDISC COP 001 (RF)
• Project Organization (RF)
• Project Process (DD)
• Project Status (DD)
• SDTM and Terminology (DD)
• Practical Experience (DD)
• Next Steps (RF)
• Core Team Contact Info (RF)

4
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

5
CDASH Project Update

• Background
• Critical Path Initiative 45 Build on work
  started by ACRO
• Jan 2006 - DIA Open Forum Creating Clinical
  Trial Efficiencies Through Standard Data
  Collection organized by CDISC, FDA, ACRO
• CDISC requested to take leadership role as
  established standards development organization
• June 2006 Initial Collaborative Group (10)
  announced by Dr. Woodcock at Annual DIA Meeting
  in Philadelphia Human Subject Protection/Bioresea
  rch Monitoring Initiative and Critical Path
  Update
• October 2006 Collaborative Project Kickoff,
  Cary N.C.

6
CDASH Project Charter

• CDASH Clinical Data Acquisition Standards
  Harmonization
• Project Charter
• To develop a set of content standards (element
  name, definition, metadata) for a basic set of
  global industry-wide data collection fields that
  support clinical research. The initial scope
  will be the safety data/domains.
• These safety domains cut across all therapeutic
  areas, beginning with approximately 12-16
  domains.
• Follow CDISC Operating Procedure for Standards
  Development (COP-001).

7
CDASH Project Update

• Collaborative Group
• Role
• To participate in the Collaborative Group
  Steering Committee, that provides expertise and
  strategic input to the CDASH Project Team and
  Streams.
• To contribute and/or help identify resources as
  deemed necessary to enable achievement of the
  mission, goals and deliverables for this project.

8
CDASH Project Update
Collaborative Group Provides expertise and
strategic input into the CDASH Initiative
Collaborative Group Members

• American Medical Informatics Association (AMIA)
• Association of Clinical Research Organizations
  (ACRO)
• Association of Clinical Research Professionals
  (ACRP)
• Baylor College of Medicine
• Biotechnology Industry Organization (BIO)
• Clinical Data Interchange Standards Consortium
  (CDISC)
• Clinical Research Forum
• Critical Path Institute
• Duke Clinical Research Institute (DCRI)

• Food and Drug Administration (FDA)
• National Institutes of Health (NIH)
• NCI-EVS
• NCI-caBIG
• Clinical Research Policy Analysis Coordination
  Program
• National Clinical Research Resources (NCRR)
• National Institute of Child Health Human
  Development (NICHD)
• Pharmaceutical Research and Manufacturers
  Association (PhRMA)
• Society for Clinical Data Management (SCDM)

9
CDASH Project Update

• Key Collaborations
• NIH
• NCI-EVS
• NCI-caBIG
• Clinical Research Policy Analysis Coordination
  Program
• National Clinical Research Resources (NCRR)
• National Institute of Child Health Human
  Development (NICHD)
• CDISC SDS Team
• CDISC Terminology Team

10
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

11
CDISC Standards Development Process (COP-001)
Primary Stages
Stage I Standard Definition/Approval Multidiscipl
inary Team Initiation Working Plan Development
Stage II Standards Development-Consensus Model
Reviews by External Focused Group and Open
Public Harmonization and Testing throughout
V1.0 Release

Stage III Education Support
Stage IV Standards Update Maintenance
12
Standards Development Process for CDISC (COP-001)
Current Status
Stage I Standard Definition/Team Initiation
Need for Specific Standard(s) Identified (any
stakeholder)
Proposal to Board of Directors (via OIS)
Review per strategy, budget priorities
Working Plan (timelines, deliverables communicati
on mech., resources reqd) (Team )
Team Leader ID And Team Formation (multidisciplina
ry) (OIS)
Approved
Not Approved
Stage II Standards Development/Review/V 1.0
Release
Testing
Consensus (Initial) Version
Harmon- ized Version
Released (Production) Version 1.0
Review Version
Comments addressed
OK
Public Review
TLC Review
Ex Focused Review
OK
Comments to address by team
Stage III Education Support
Respond To Comments And Questions
Educational Programs (EDU, OIS)
SPCC Review
Stage IV Standards Update Maintenance
NewReleased (Production) Version
Annual Review of Released Version (comments,
chg reqsts, tests, plans)(Team)
Working Plan(timelines, deliverables,communicat
ion mech.,resources reqd)(Team)
Consensus(Revised)Version
Harmon-ized Version
Public Reviewasneeded
Optional
Ex Focused Review
Note Occasional bug fix releases may be issued
as needed with team review only.
13
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

14
CDASH Project Update
CDASH Collaborative Group
CDISC Technical Leadership Committee
CDISC Technical Advisory Committee
Core Team
Stream Members

• 9 CDASH Streams (sub-groups)
• Comprised of 190 volunteers

15
CDASH Project Update
Project Organization

• Stream membership
• Statisticians
• Medical Monitors/Clinical Scientists
• Regulatory Affairs
• Drug Safety
• Data Managers
• Clinical Study Coordinators
• Clinical Research Associates
• Investigators
• Clinical Program Managers
• Statistical Programmers
• Database programmers
• e Vendors
• Need more multi-national input!

Participants in the CDASH Initiative
Other Academic Research Organizations,
Government (NIH, NCI), Hospitals, Universities.
16
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

17
CDASH Project Update
Process

• Guiding principles variables should
• Address either directly or indirectly SDTM
  required elements
• Be standard but flexible to allow customization
  within defined limits
• Limit variables to required and necessary
• Comply with regulatory requirements
• Reduce redundancies
• Increase collection of meaningful data
• Facilitate use of standards by all users
• Be appropriate for use both pre and post approval
  studies
• Allow consistent and efficient data
  collection/storage/transmission and analysis

ACROs development principles, CDASH Kick-off
Meeting, October 2006, Cary, N.C.
18
CDASH Project Update

• CDASH Getting Started
• Start with Study Data Tabulated Model (SDTM) Data
  Variable Tables
• Refer to ACRO CRF Samples (where available)
• Initial Focus on CRF Content, not CRF Layout
• Collect CRF samples
• Evaluate commonalities/differences of CRF samples
  and SDTM
• Document data points included/excluded with
  justifications

19
CDASH Project Update

• Process Deliverables
• Reach agreement on basic CRF Data collection
  variables
• Map to SDTM - in cooperation with the SDTM
  development team
• Terminology Provide Terminology proposals to
  the Terminology team
• Add definitions
• Write completion guidelines/instructions
• Proceed to the next step in the Consensus Process
  as specified in COP-001
• Technical Leadership Committee (TLC)

20
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

21
CDASH Project Update

• CDASH Package-1 Adverse Events, Concomitant
  Medication, Demographics Subject
  Characteristics
• Oct. 2006 launch at Project Kick-off meeting
• TLC and Collaborative Group (CG) reviews are
  completed
• CG comments are now being addressed and a
  Reviewed Version achieved

Consensus (Initial) Version
Harmon- ized Version
Released (Production) Version 1.0
Review Version
OK
Public Review
TLC Review
Collaborative Group Review
OK
22
CDASH Project Update
Basic Data Collection Fields Identified

• DM SC
• Year of Birth (BRTHDTC)
• Month of Birth (BRTHDTC)
• Sex (SEX)
• Race of Subject (RACE)
• Year of Birth (BRTHDTC)
• Month of Birth (BRTHDTC)
• Sex (SEX)
• Race of Subject (RACE)

• AE
• Adverse Event Term (AETERM)
• Start Date (AESTDTC)
• Stop Date (AEENDTC)
• Seriousness (AESER)
• Relationship (AEREL)
• Action Taken (AEACN)
• Outcome (AEOUT)
• AE Severity (AESEV)
• or AE Toxicity (AETOXGR)

• CM
• Reported name of Drug, Medication or Therapy
  (CMTRT)
• Start Date (CMSTDTC)
• Stop Date (CMENDTC)

• DM
• Year of Birth (BRTHDTC)
• Month of Birth (BRTHDTC)
• Sex (SEX)
• Race of Subject (RACE)

Optional data collection variables have also been
identified. Variable names are from the SDTM.
23
CDASH Project Update

• CDASH Package-2 Inclusion/Exclusion Criteria,
  Medical History Substance Use, Physical Exam
  Vital Signs
• Dec. 2006 launch
• TLC and Collaborative Group (CG) reviews are
  completed
• CG comments are now being addressed and a
  Reviewed Version achieved

Consensus (Initial) Version
Harmon- ized Version
Released (Production) Version 1.0
Review Version
OK
Public Review
TLC Review
Collaborative Group Review
OK
24
CDASH Project Update

• CDASH Package-3 Drug Accountability Exposure,
  Comments Deviations, Disposition/End of Study
• Mar. 2007 launch
• TLC review complete
• Collaborative Group review start December 5.

OK
25
CDASH Project Update

• CDASH Package-4 Lab ECG
• July 2007 Launch
• Lab ICV delivered now under TLC review
• ECG ICV due ASAP
• CG review planned for December 2007

26
CDASH Project Update
27
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

28
FDA - Proposed Rule
Federal Register / Volume 71, No. 237 /Monday,
December 11, 2006

• require (not just accept) electronic submissions
• require submissions to be in the SDTM format
• proposed 2 year implementation (actual proposed
  rule not yet written)

29
AE Relatedness Example
AE Relatedness to Study Drug (CDISC AEREL, no
standard codelist defined)

• Company 2
• Not Related
• Doubtful
• Possible
• Very Likely
• Probable

• Company 3
• NO
• YES / Unknown

• Company 1
• No
• Unlikely
• Possible
• Probably
• Definite

30
SDTM Terminology Projects

• SDTM Package-1 30 code lists more than 700
  controlled terms - Now in production
• Labtest single code list with 92 controlled
  terms - Now in production200 additional Analyte
  terms in development and available for public
  review Q4 2007
• SDTM Package-2A 12 code lists more than 600
  controlled terms for ECG, Con Meds, Drug Exposure
  and Substance Use, including Units of Measure
  completed Public Review
• SDTM Package-2B 17 code lists 500 controlled
  terms for AE, Physical Exam, Vital Signs and
  Subject Chars, including Anatomical Location in
  development

31
Harmonization Activities

• CDASH aligning SDTM terminology projects with
  CDASH requirementsfull harmonization planned for
  Q1 2008
• CDASH Questions
• Terminology Answers

32
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience (DEMO)
• Next Steps
• Core Team Contact Info

33
Practical Experience Goal
1. ACRO Standard Form
4. Annotated Form ODM Standard Standard
electronic metadata (XML)
ltODMgt ltStudygt ltMeta lt/Meta
lt/Studygt lt/ODMgt
5. Standard electronic metadata configures
collection system
3. ACRO Form SDTM Standard Annotated Form
2. CDISC SDTM Standard
34
ACRO Adverse Event Form
35
Annotated Version
36
Electronic Configuration
Courtesy of Assero
37
Electronic Configuration
Courtesy of Formedix
38
Courtesy of XClinical
39
Courtesy of Outcome
40
CDASH Project Update

• Integrating the Healthcare Enterprise (IHE)
• Patient Care Coordinating Committee (PCCC)
• Electronic Health Records (EHR)
• Facilitate Single Source data entry.
• CDASH data collection elements to be used to
  create a profile, that can be used to populate a
  basic eCRF.

41
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• SDTM and Terminology
• Practical Experience
• Next Steps
• Core Team Contact Info

42
CDASH Project

• Standardize basic therapeutic area data variables
  (cooperate with other ongoing initiatives)
• Devices
• Imaging
• CDISC Supported Activities
• New Domains to be CDASHed
• Periodic update/revision of CDASH developed
  domains and documentation (Stage IV of COP-001)
• Training

43
CDASH Project Update

• Background, Charter and the Collaborative Group
• CDISC COP 001
• Project Organization
• Project Process
• Project Status
• Practical Experience
• SDTM and Terminology
• Next Steps
• Core Team Contact Info

44
CDASH Project Process

• CDASH Core Team Contact Information
• Rhonda Facile rfacile_at_cdisc.org
• Gary Walker gary.walker_at_quintiles.com
• Dorothy Dorotheo DDorotheo_at_intermune.com
• David E. Tatum tatum4_at_comcast.net
• Paul Bukowiec Paul.Bukowiec_at_mpi.com
• Trisha Simpson Trisha.Simpson_at_schwarzbiosciences.c
  om
• Shannon Labout slabout_at_csscomp.com
• Liz Nulton-Bodiford liz.m.nulton-bodiford_at_gsk.com
• Jay Leeka Jay.Leeka_at_astrazeneca.com
• Alec Vardy a.vardy_at_comcast.net
• Kim Truett Kim.Truett_at_kctdm.com

45
CDASH Project Process

• Thanks to all the volunteers who have
• worked to get us where we are today.
• GET INVOLVED!
• contact
• rfacile_at_cdisc.org
• DDorotheo_at_intermune.com
• Bron Kisler (Terminology) bkisler_at_cdisc.org

46

• Knowing is not enough we must apply
• Willing is not enough we must do

Goethe