1. Clinical Data Interchange Standards Consortium Overview
HCLSIG BioRDF Sub-group 10 Mar 2008
Clinical Data Interchange Standards Consortium Overview
Stephen J Ruberg, PhD
Senior Research Fellow
Eli Lilly & Company

2. Background Who is Steve Ruberg?
How does pharma generate and utilize clinical data?
What is CDISC?
What has CDISC done, what are they doing, and what are they considering?
Where does CDISC need help?

3. Steve Ruberg Statistician
Not IT, though much learning over last decade
Creator, recipient, analyzer, archiver, submitter of clinical data
Helped launch CDISC as not-for-profit in 2000
First Chairman; just finished my term on the Board in Dec, 2007

4.  Pharma Clinical Data Company executed trial
Getting data from investigators
Paper and electronic
Getting data from labs
Central vs local
Getting data from other sources
Growing variety of electronic data capture

5. Electronic Data Capture at an Investigator Site

6.  Pharma Clinical Data Other considerations Working with a CRO
Defining data specs
Receiving datasets
Submissions to the FDA
Observed/raw data and derived/analysis data
Analysis programs, reports

7.  Pharma Clinical Data Value of Standards Operational efficiency
Reduce programming and re-mapping of data
Increase automation; better tools
Scientific effectiveness
INTEGRATION OF DATA
Better analysis, interpretation, understanding
FDA remit: Promote and protect health

8. What is CDISC
CDISC is a global, open, multidisciplinary, non-profit organization that has established standards to support the acquisition, exchange, submission and archive of clinical research data and metadata. The CDISC mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.  CDISC standards are vendor-neutral, platform-independent and freely available via the CDISC website.
Established as a non-profit in 200
Most members from pharma or companies (CROs, software vendors) that support pharma clinical research

9. What is CDISC Doing CDISC models
SDTM – Submission Data Tabulation Model (used for FDA submissions; can also be used for CRO submissions to pharma sponsor)
Defines structure (vertical) and some categorization/data domains and minimal terminology
ODM – Operational Data Model
XML messaging standard
LAB – Clinical laboratory data model

10. What is CDISC Doing CDISC models
SEND – Standard for Exchange of Non-clinical Data
Non-clinical version of SDTM
Used for FDA submissions; can also be used for CRO submissions to pharma sponsor
Defines structure (vertical) and some categorization/data domains and minimal terminology
ADaM – Analysis Data Model
Suggested structures for FDA submission of analysis data
Protocol Representation Group
Terminology/data definitions to describe a protocol/study

11. What is CDISC Doing CDISC models
CDASH – Clinical Data Acquisition Standards Harmonization
Non-clinical version of SDTM
Used for FDA submissions; can also be used for CRO submissions to pharma sponsor
Defines structure (vertical) and some categorization/data domains and minimal terminology
ADaM – Analysis Data Model
Suggested formats for FDA submission of analysis datasets
Terminology
Creating more detailed data element specifications for use in SDTM

12.  What is CDISC Doing CDISC works in virtual teams
Conference calls, meetings
Tends to focus on pieces (data domains like adverse events, demography, vitals signs, etc.) of the clinical business
Progress, but slow and limited

13. What is CDISC Considering
What is CDISC Considering
CDISC models have some utility but cannot meet data integration needs
Not enough unambiguous data element definitions (i.e. terminology)
Caution: terminology means different things to different people
Concept
Valid value set

14. 
Proposal
WHAT
Build a comprehensive, industry-wide electronically accessible and consumable data element dictionary that contains the “clinical words” used in clinical research studies

15. What Is a Data Element Definition?
What Is a Data Element Definition?
All the pieces of information (i.e. attributes) needed to unambiguously describe a concept
English dictionary analogy
Word – desk
Phonetic spelling – dĕsk
Part of speech – noun
Definition – a piece of furniture with a flat top for writing
[could also be thought of as the concept]
Source – Latin, discus
etc.

16. The English Dictionary as Attributes
The English Dictionary as Attributes
Word
Phonetic spelling
Part of Speech
Definition
Source
Year
Other Forms
Synonym / Example
desk
dĕsk
Noun
1. A table, frame or case with horizontal or slightly sloping surface for writing or reading
Latin, discus
Old English
None
counter
2. A division of an organization specializing in a particular activity
e.g. the Russian desk at the State Department
run
rən
Verb
1. To go faster than a walk by springing the feet so that only one is touching the ground at a time
Old English, iernan
run across
run a fever
Sprint, jog, scuttle, dart, scamper, dash
Something that flows in the course of an operation
Operate, conduct

17. Clinical Data Element for Pharma
Clinical Data Element for Pharma
DRAFT
DRAFT
Variable name
Label / concept
Valid values of the variable itself
Data type (num, char, date, …)
Units
Key words (e.g. biomarker, osteoporosis, …) – facilitate searches
Source / reference (as needed)
SDTM data domain
Regulatory requirement
[A team needs to define what are the essential attributes that are parsimonious – enough to eliminate ambiguity, but few enough to be useful, consumable, understandable, burdenless.]

18. The Clinical Data Element Dictionary
The Clinical Data Element Dictionary
Variable Name
Concept / Label
Data Type
Format
Valid Values
Units
SDTM Domain
Source
Keywords
URL
HAMD_Q1
Response to question #1 on the Ham-D 21 Depression Scale
Num I1
0,1,2,3,4 NA NS
“A rating scale for depression”
1960
Max Hamilton
Journal of Neurology, Neurosurgery and Psychiatry. vol 23 pp 56-62
Depression, rating scale, questionnaire, mood
HAMD_Q16
Response to question #16 on the Ham-D 21 Depression Scale
0,1,2,3
As above
Depression, rating scale, questionnaire, weight loss
AE_verb
Verbatim adverse event reported by the investigator
Char
200
English text AE
See GCP
Safety, risk, drug reaction, side effect, treatment-emergent
AE_LLT
Coded adverse event using the MedDRA lowest level term 50
Lowest level terms from MedDRA
See MedDRA reference

19.  Proposal HOW - Business model
An open, electronic, peer production environment with appropriate governance (e.g. a wiki)
Like MedDRA, but open and free
Like Wikipedia, but more governance
Like LINUX, but more granular and dynamic
We must adopt a more flexible and rapid development process to get this in place

20. Clinical Data Element Standards
Electronic submission
Governance
Template
Submission
Review
Final
Anyone
Anywhere
Based on 8-10 attributes
Downloadable (define.xml)
Searchable – text, key words
search shows status (submit, review, final)

21. Governance for the CDED
Governing Board
Full-Time CDISC Employees
Lead 1
Lead 2
Lead Lead k
Team 1
Team 2
Team 3
Team k
Lead 1
Lead 2
Lead 3
Lead k
. . .
~ 6-8 SME’s
~ 6-8 SME’s
~ 6-8 SME’s
~ 6-8 SME’s

22. 
Next Steps
CDISC is considering this need (data element dictionary) and seems to be moving in this direction
Make your voice heard to CDISC if you see the value
Create a sense of urgency as you see fit
CDISC is considering the wiki approach
Let me and/or CDISC know of your willingness to contribute to a wiki
We could build this together much faster
Requires a new business model / approach
Can W3C give advice, input or help?