CDISC Controlled Terminology
across the Clinical Trial Continuum
Bay Area Implementation Network
6 March 2008
Bron Kisler
Co-Founder / Director of Terminology
CDISC Terminology Initiative
ƒ Overview / Background
ƒ Terminology Development /
Harmonization
ƒ Production Spreadsheet
ƒ TB & Cardiology Projects
Terminology Program Snapshot
• Formalized CDISC Terminology Program in 2005, initially
focusing on SDTM terminology requirements
• Primary Objective: to develop and align terminology across
all CDISC standards, spanning the clinical trial continuum
(SDTM ↔ CDASH)
• Terminology Team comprised of 60+ team members (Global
Pharmas, Regulators, Academia, CROs, etc.) with work
distributed across 4 project teams
• Key partnership with US National Cancer Institute Enterprise
Vocabulary Services (NCI EVS)
• Combined CDISC Terminology & HL7 RCRIM Vocabulary
teams to ensure common development
Working Principles
• Evaluate and/or utilize existing terminology 1st
• Expand existing vocabularies where incomplete,
working with vocabulary developer / owner
• Harmonize across CDISC Models and with preexisting vocabulary initiatives
• Address international needs for global projects
and organizations
• Ensure a sustainable “open source” environment
and infrastructure for production terminology
supporting terminology evolution
NCI EVS Partnership
• Dedicated terminology experts and resources
• CDISC controlled terminology development,
harmonization, publication and maintenance
• CDISC work space in NCI Thesaurus with
supporting infrastructure
• NCI EVS supports FDA vocabulary initiatives
– SPL, ICSR and RPS
Proposed Rule
(key driver)
The Food and Drug Administration is
proposing to amend the regulations
governing the format in which clinical
study data and bioequivalence data are
required to be submitted for new drug
applications (NDAs), biological license
applications (BLAs), and abbreviated
new drug applications (ANDAs). The
proposal would revise our regulations
to require that data submitted for
NDAs, BLAs, and ANDAs, and their
supplements and amendments be
provided in an electronic format that
FDA can process, review, and archive.
The proposal would also require the
use of standardized data structure,
terminology, and code sets contained in
current FDA guidance (the Study Data
Tabulation Model (SDTM) developed
by the Clinical Data Interchange
Standards Consortium) to allow for
more efficient and comprehensive data
review.
Federal Register / Volume 71,
No. 237 /
Monday, December 11, 2006
SDTM 3.1.1 Domains
Interventions
Findings
Events
Exposure
Labs
InclExcl
AE
ConMeds
Vitals
SubjChar
Disp.
Subst Use
PhysExam
ECG
MedHist
Adverse
Events
QS
**50+ SDTM fields identified as candidates for controlled terminology codelists
AE Relatedness field - AEREL
AE Relatedness to Study Drug?
(No standard Codelist defined)
Company 1
Company 2
Company 3
•
•
•
•
•
•
•
•
•
•
• NO
• YES / Unknown
No
Unlikely
Possible
Probably
Definite
Not Related
Doubtful
Possible
Probable
Very Likely
AE Relatedness field - AEREL
AE Relatedness to Study Drug?
(Standard Terminology Codelist aka “Value Set”)
Standard Codelist
CDISC
Controlled
Terminology
•
•
•
•
•
No
Unlikely
Possible
Probably
Definite
AE Relatedness field - AEREL
AE Relatedness to Study Drug?
(Standard Terminology across CDISC Standards)
CDASH
SDTM
SEND
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
No
Unlikely
Possible
Probably
Definite
No
Unlikely
Possible
Probably
Definite
No
Unlikely
Possible
Probably
Definite
Terminology Development &
Harmonization
SDTM Terminology
(production ~1600 terms)
• SDTM Package 1: 31 codelists & 825 controlled terms
distributed broadly across SDTM
• Labtest Package 1: 2 codelists with 180 controlled
terms for Analytes
• SDTM Package-2A: 7 code lists & 590 controlled terms
for ECG, Con Meds, Drug Exposure and Substance
Use, including Units & Frequency
• http://www.cancer.gov/cancertopics/terminologyresources/
• New Activities: assess production representation and
usability; change requests & governance; maintenance
& versioning (aligned with MedDRA)
SDTM Terminology
(development ~650 terms)
• SDTM Package-2B:
– 12 code lists & 350 controlled terms developed and available for public
review (AE, PE, VS and Subject Chars)
– Includes terminology set for anatomical location (SDTM LOC fields);
both NCI Thesaurus and SNOMED were considered to be wellrepresentative of needs
• Labtest Package 2/3:
– SDTM: 200+ additional terms developed and available for public
review (Labtest Package 2)
– SDTM/SEND: 100 terms in development for Vitamins, Enzymes,
Immunology, Common drugs from drug screen (Labtest Package 3)
– Ongoing discussions with LOINC
• New SDTM projects to be launched in March per
terminology gap analysis (SDTMIG 3.1.1, CDASH)
Internal Harmonization
•
CDISC Glossary: to be represented in EVS NCI
Thesaurus environment with SDTM terminology
•
CDASH: aligning SDTM terminology with CDASH
requirements; harmonization timeline pending
SDTM-CDASH gap analysis
•
SEND: initial gap analysis with SDTM complete;
joint development activities underway
•
BRIDG (HL7 RCRIM): high level analysis complete
and harmonization plans in discussion
US Federal Harmonization
ICD’s
LOINC
SNOMED
MedDRA
MeSH
NCI Thesaurus
.
.
.
60+
Controlled
Vocabularies
External Harmonization
(semantic links to healthcare)
•
ISO: Global harmonization via ISO TC215
WG6 per proposal from ICH; participating
standards organizations – ISO, ICH, CEN, HL7
& CDISC
•
LAB: discussing solution to link SDTM Labtest
values with LOINC codes
•
TB & Cardiology: CDISC and HL7 style
“artifacts” released for public review
•
Other: Imaging, Microbiology, PGx, Medical
Devices
2008 Terminology Priorities
1. Finalize terminology needed for SDTM IG Ver 3.1.1
2. Support / harmonize with other priority CDISC
projects – CDASH, SEND, Glossary, BRIDG
3. Support projects via HL7 RCRIM – BRIDG, FDA
Projects, CDISC-HL7 Message
4. Change control, governance and versioning
5. Develop integrated implementation plan to align
terminology with other CDISC standards
6. New SDTM 3.1.2 domains and semantic links with
healthcare
Production Spreadsheet
Tuberculosis (TB) &
Cardiology (CV) Projects
Sponsored by the US
National Institutes of Health
Primary Aim: Improve interoperability by
standardizing
CV
&
TB
data
elements
NIH ROADMAP FOR MEDICAL RESEARCH
RE-ENGINEERING THE CLINICAL RESEARCH ENTERPRISE
( CV & TB grants awarded to Duke University in 2005 )
Data Element: TB example
Data Element Name: Reason subject first came to medical
attention
Clinical Definition: The reason the subject was first
medically evaluated for possible TB disease or latent TB
infection.
Valid Values: (enumerated)
Symptoms
Contact investigation
Source case investigation
Screening of High Risk Population
Other (Specify)
Unknown
Key Objectives
Develop and publish an initial set of CV & TB
specific data standards – clinical data elements,
definitions and value sets
Leveraging CDISC and HL7 standards processes,
focus on methodology for developing therapeutic
area data standards using case studies
Produce useful products for CV & TB and report
experience, process and best practices
Parallel Universes
Patient Care
World
Clinical Research
World
TB: Diagnosis & Treatment of Pulmonary TB
CDISC
Healthcare Link
CDISC
Standard Terminology
EHR
CDASH
SDTM
(health record)
(data collection)
(submission)
BRIDG Model
Results – CDISC & HL7 Artifacts
•
•
•
•
•
•
Use cases and storyboards (H)
Data elements and clinical definitions
Domain Class model (H)
Domain Activity diagram (H)
Data collection forms (R)
SDTM representation (R)
H = Healthcare / R = Research / U = Universal
(U)
TB Data Standards Working Group
• Aeras Global TB Vaccine
Foundation (Gates funded)
• Centers for Disease Control
& Prevention (CDC)
• CDISC
• Duke University Med. Center
• FIND Diagnostics (Gates
funded)
• Global TB Alliance (Gates
funded)
• Health Level 7
• National Cancer Institute
• National Heart, Lung &
Blood Institute (NHLBI)
• National Institute of Allergy
and Infectious Diseases
(NIAID)
• National TB Control Assoc.
• Otsuka
• Tibotec (a J&J company)
• WHO Stop TB Partnership
• Other Global Pharmas
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.