1. CDISC Standards: Connecting Clinical Research and Healthcare
NCBO Meeting
Signs, Symptoms and Findings
3 September 2008, Dallas TX
Bron Kisler (CDISC)
Gary Walker (Quintiles)

2. Strength through collaboration.
CDISC operates to advance the continued improvement of public health
by enabling efficiencies in medical research and related areas of healthcare.
Strength through collaboration.
As a catalyst for productive collaboration, CDISC brings together
individuals spanning the healthcare continuum to develop
global, open, consensus-based medical research data standards. 2

3. CDISC Standards Description 2004* 2001* 2005* 2002 2004 Fall 2008
Implementation Version Release Date
SDTM, SEND
Ready for regulatory submission of CRT
Over 10,000 downloads as of late-2007
2004*
ODM
CDISC Transport Standard for data interchange (acquisition, exchange, documentation and archive)
2001*
Define.xml
Case Report Tabulation Data Definition Specification (submission documentation)
2005*
LAB
Content standard – available for transfer of clinical lab data to sponsors
2002
ADaM
Analysis data for submissions - general considerations document and examples
2004
Protocol
Representation
Collaborative effort to develop machine-readable standard protocol with data layer
Fall 2008
Terminology
Codelists
Developing standard terminology to support all CDISC standards
Package1
Package2
CDASH
Data acquisition (CRF) standards
Sept. 2008
* Specification referenced via FDA Final Guidance

4. Data Flow Using CDISC Standards
= ODM - Operational Data Model (transport of data and metadata…”the message”)
= SDTM - Study Data Tabulation Model and ADaM - Analysis Dataset Model (content)
SEND for Non-clinical Data
= Protocol Representation Standard (content)
= Source data
(other than SDTM/CRF data)
= LAB – Laboratory Data Standard
Protocol
Representation
Integrated
Reports
Patient Info
Lab Data
CDASH-eCRF
Study Data
(defined by
SDTM)
Study &
Analysis
Data
Study &
Analysis
Data
Trial Design
Analysis Plan
ODM
XML
ODM
XML
ODM XML
Define.xml
Study
Protocol
(e)Source
Document
Operational & Analysis
Databases
Reporting or
Regulatory
Submissions
Warehouse 4

5. Submissions – SDTM version 3.1.2
Interventions
Exposure
Conmeds
SubstUse
Events AE
Deviations
Disposition
MedHx
Clinical
Findings
Vitals
Labs
ECG
Incl/Excl
SubjChar
Ques’aire
Micro MS
Micro MB
DrugAcct
PhysExam
PK Param
PK Conc
Demog
Special
Purpose
Comments
SUPPQUAL
Trial Design
(5 Tables)
RELREC
SubjElements
SubjVisits
SDTM = Study Data Tabulation Model

6. SDTM General Observation Classes
Interventions class captures investigational, therapeutic and other treatments that are administered to the subject (with some actual or expected physiological effect) either as specified by the study protocol (e.g., “exposure”), coincident with the study assessment period (e.g., “concomitant medications”), or self-administered by the subject (such as alcohol, tobacco, or caffeine)
Events class captures planned protocol milestones such as randomization and study completion (“disposition”), and occurrences, conditions or incidents independent of planned study evaluations occurring during the trial (e.g., “adverse events”) or prior to the trial (e.g., “medical history”)
Findings class captures the observations resulting from planned evaluations to address specific tests or questions such as laboratory tests, histopathology, ECG testing, and questions listed on questionnaires. Most findings are measurements, tests, assessments, or examinations performed on a subject in the clinical trial

7. CDISC Terminology Snapshot
Formalized CDISC Terminology Initiative in 2005
Primary Objective: to define and support the terminology needs of the CDISC models across the clinical trial continuum (SDTM → CDASH)
Focus on “standard” terminology development and publication, beginning with SDTM ver3.1.1
Key partnership with US National Cancer Institute Enterprise Vocabulary Services (NCI EVS)
External harmonization: ISO, HL7 RCRIM, FDA, HITSP, NCI, etc.
Controlled Terminology represents one of CDISC’s broadest and most ambitious initiatives.
We formalized…
Primary Objective…across the clinical trial continuum from the point of data collection through to eSubmissions

8. CDISC Controlled Terminology
LOINC
SNOMED
MedDRA
MeSH
ICD’s .
60+
Controlled
Vocabularies
NCI Thesaurus

9. Clinical Data Acquisition Standards Harmonization
CDISC-led Project (initiated by ACRO) to address FDA Critical Path Initiative Opportunity #45
Mission: To develop a set of ‘content standards’ (element name, definition, metadata) for a core set of global data collection fields that will support clinical research studies.
Scope: The initial scope is focused on the ‘safety data/domains’ common across all therapeutic areas
Process: Begin with and map to SDTM version 3.1.1; focus on ‘CRF content’ not layout; collect CRF samples and id commonalities; work with Terminology Team on terminology proposals; follow CDISC consensus process 9 9

10. CDASH Collaborative Group
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 & Drug Administration (FDA)
NIH - NCI - caBIG
NIH - Clinical Research Policy Analysis & Coordination Program
National Clinical Research Resources (NCRR)
NIH - National Institute of Child Health & Human Development (NICHD)
National Library of Medicine (NLM)
Pharmaceutical Research and Manufacturers Association (PhRMA)
Society for Clinical Data Management (SCDM) 10 10

11. CDASH-ODM Connection

12. Creating CDASH-ODM Template
<Study>
<Meta …
</Meta
</Study>
</ODM>
CDASH–ODM
Template
CDASH Content
SDTM - Study Data
Tabulation Model
Terminology
Codelists
Presentation
Extended ODM
ODM - Operational
Data Model
(Database Content
and Structure) 12

13. ODM Building Blocks How does CDASH Relate?
Clinical Database
Variable Name
CDASH CRF
Label/Question
CDASH Core
(Highly Recommended)
Controlled Terminology

14. Optimal Solution from Standardized Content to any EDC System
I have an alternative to this diagram – this is new. Good because it brings in libraries ……

15. Multi-Vendor Visualizations – PhaseForward15

16. Multi-Vendor Visualizations - Medidata16

17. CDISC ‘Healthcare Link’

18. Data Flow Using CDISC Standards linking clinical research & healthcare
Electronic
Health Record
= SDTM and Analysis Data (content)
= ODM (transport)
= Protocol information (content)
= Source data
(other than SDTM/CRF data)
Patient Info
HL7 and/or
ODM XML
HL7 and/or
ODM XML
Clinical Trial
Data
Integrated
Reports
Protocol
Representation
Patient Info
Lab Data
CDASH-eCRF)
Study Data
(defined by
SDTM)
Study &
Analysis
Data
Study &
Analysis
Data
Study Design
Analysis Plan
ODM
XML
ODM XML
Define.xml
ODM
XML
Operational & Analysis
Databases
Study
Protocol
(e)Source
Document
Regulatory
Submissions 18 18

19. Workflow Integration: RFD
Clinical Research
Sponsor
Data Receiver
Receives the data instance from the Form Filler.
Forms Manager
Serves up the form to the Form Filler.
Case Report Form (CRF)
CDASH
ODM
Forms Filler
Displays the form for completion in an EHR session
EHR
Data Archiver
Stores the electronic
source document
Primary Use
RFD = Retrieve Form for Data Capture 19

20. RFD Proof of Concept Lilly/Quintiles RFD 20 3. Form Manager
pre-populates Lilly S001 form and returns to Form Filler who completes and submits the form
4. Data Receiver
Receives and inserts data into Phase Forward’s Clintrial CDMS.
Lilly/Quintiles
Form
Manager
Data
Receiver
CDASH data elements (demographics, AE, meds) hit 25/33 slots in Lilly CRF.
ODM + XForms allowed 4 EHRs to render the form on the first try!
RFD
2. Form Filler forwards CDASH data elements to the Form Manager (to retrieve a pre-populated form)
Form
Filler
5. Data Archiver stores the electronic source document.
Data
Archiver
Cerner
Millennium
1. Site Investigator uses Cerner Millenium to retrieve an electronic case report form. 20

21. Other Healthcare Links

22. CDISC Standards & BRIDG Model (Biomedical Research Information Domain Group)
Submissions
Analysis Data
SDTM / SEND
Glossary
ODM
LAB
ADaM
CDASH
Data Collection
Protocol
BRIDG is a
mechanism
for standards
integration 22

23. BRIDG as a portal to Healthcare
Submissions
CDASH
Data Collection B R I D G
Glossary
Healthcare
SDTM / SEND
Protocol B R I D G
ODM
ADaM
HL7 RIM
LAB
Analysis Data 23

24. BRIDG Domain Analysis Model
(implementation independent)
The value of the BRIDG model is in the disambiguation
Forces the semantics into a visual representation
Models the “problem space” of protocol-driven clinical research
This is an example of a class diagram for BRIDG that depicts classes, relationships, etc.

25. FDA IT Plan (CDISC-HL7 Message)
Site
Sponsor
CDISC Content and Interchange
Interchange:
HL7 output file
CDISC Content
Trial Design
CDASH
Data Checker
and Loader
Sponsor
Data
Warehouse
(ODM)
FDA Reviewers
SDTM
ADaM
Janus
FDA/NCI
Analytical Data
Warehouse
Review
Tools
Site Data
Archive
(ODM)
MedWatch AE Reports (ICSR)