CDISC Standard Controlled Terminology across the Clinical Trial Continuum

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CDISC Standard Controlled Terminology across the
Clinical Trial Continuum
2007 DIA Annual Meeting (adapted for OCI Work
Group) Atlanta, GA / June 20, 2007 Session (IT)
Standard Controlled Terminology A Successful
Partnership between CDISC, the FDA and NCI EVS

• Bron W. Kisler
• Co-Founder / Terminology Program Director

Clinical Data Interchange Standards Consortium
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CDISC Terminology Initiative

• CDISC Overview
• Why Standard Terminology?
• Terminology for SDTM
• NCI EVS Partnership
• The Home Stretch

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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

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CDISC Standards
Specification referenced in FDA Final Guidance
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CDISC Technical Roadmap Plan
CDISC harmonization milestones
BRIDG (Biomedical Research Integrated Domain
Group)
A
B
C
D
LAB
The CDISC Standard
LAB SDTM
LAB, SDTM, ODM DEFINE.XML
LAB, SDTM, ODM, DEFINE.XML ADaM
SDTM
ODM
ODM
DEFINE.XML
DEFINE.XML
ADaM
ADaM
ADaM
PROTOCOL
PROTOCOL
PROTOCOL
PROTOCOL
CDASH
CDASH
Controlled Terminology
2006
2006-2010
2005
2005-2006
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FDA endorses CDISC standards by including them as
specifications in FDA Final Guidance
Study Data Tabulation Model (SDTM), define.xml
(CRTDDS), Operational Data Model (ODM)
Specifications for FDA implementation of the
ICH eCommon Technical Document
October 2005 Federal Register Notice of
Proposed Rule and listed as DHHS Priority
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Proposed Rule
Federal Register / Volume 71, No. 237 /Monday,
December 11, 2006
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.
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Proposed Rule
Federal Register / Volume 71, No. 237 /Monday,
December 11, 2006
FDA considered issuing a guidance document
outlining the electronic submission and the
standardization of study data, but not requiring
electronic submission of the data in the
standardized format. This alternative was
rejected because the agency would not fully
benefit from standardization We also considered
a number of different implementation scenarios,
from shorter to longer time periods. The
two-year time period was selected because the
agency believes it would provide ample time for
application to comply without too long a delay in
the effective date. A longer time period would
delay the benefit from the increased efficiencies
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CDASH Project(FDA Critical Path Opportunity 45)

• Clinical Data Acquisition Standards Harmonization
  Initiative Project Charter
• To develop a set of content standards (element
  name, definition, metadata) for a core set of
  global industry-wide data collection fields that
  will support clinical research studies. The
  initial scope will be the safety data/domains
  to support clinical trials.
• These safety domains cut across all therapeutic
  areas, beginning with approximately 12-14
  domains.
• Follow CDISC Operating Procedure (COP) for
  Standards Development.

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CDASH Project Update
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Why is...
Standard Controlled Terminology
...Important?
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Interoperability Ability of two or more
systems or components to

• Exchange information (Syntactic Interoperability)
  and
• Predictably use the information that has been
  exchanged (Semantic Interoperability)

Source IEEE Standard Computer Dictionary
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Semantic Interoperability(the Human Factor)
SHELL
Receiver
shall we go now ?
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Semantic Interoperability(in eClinical Systems)
Term
Receiver

• Unique Preferred Term (PT)
• Consensus-based Definition
• Unique Numeric Code (CUI)
• Associated Synonyms
• Accessible Publishing Env.

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Semantic Interoperability(in Regulated Clinical
Research)
The mission of CDISC is to develop and support
global, platform-independent data standards that
enable information system interoperability to
improve medical research and related areas of
healthcare
SDTM (Submission Standard) Syntactic
Interoperability SDTM Standard Terminology
Semantic Interoperability
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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
• Definite
• Probably

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AE Relatedness Example
AE Relatedness to Study Drug (CDISC AEREL, with
standardized codelist)

• Standard Codelist
• No
• Unlikely
• Possible
• Definite
• Probably

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Connecting Parallel Universes
Patient Care World
Clinical Research World

• Healthcare data from
• multiple data sources
• Data is patient-centric
• HL7 Pervasive Standard
• Medical Records assembled
• from multiple Sources

• Research data is
• carefully controlled
• Data is trial-centric
• CDISC Emerging Standard
• Data flows from site to CRO
• to sponsors to regulatory

Neededshared semantics common data
elements
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Terminology for SDTM
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CDISC Terminology

• 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)
• Terminology Initiative comprised of 70 team
  members (Global Sponsors, Regulatory, Academia,
  CROs, etc) distributed across 4 project teams
• Key partnership with US National Cancer Institute
  Enterprise Vocabulary Services (NCI EVS)
• Combined HL7 RCRIM Vocabulary CDISC Terminology
  teams to ensure common development

SDTM Study Data Tabulation Model
(eSubmissions) CDASH Clinical Data Acquisition
Standards Harmonization RCRIM Regulated
Clinical Research Info. Management
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SDTMSyntactic Interoperability
Interventions
Findings
Events
Exposure
Labs
InclExcl
AE
ConMeds
Vitals
SubjChar
Disp.
Subst Use
ECG
PhysExam
MedHist
PG
QS
MB
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SDTM Terminology Projects

• SDTM Package-1 30 code lists more than 700
  controlled terms - Now in production!
• Labtest single code list in production with 92
  controlled terms - Now in production! 200
  additional Analyte terms in development
• SDTM Package-2A 12 code lists more than 600
  controlled terms for EG and Interventions domains
  (CM, EX, SU), including Units of Measure in
  Public Review
• SDTM Package-2B 17 code lists likely 1500
  controlled terms for AE, PE, VS and SC domains
  including Anatomical Location in development

SDTM Study Data Tabulation Model
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SDTM Package-1 (30 Terminology Code Lists)

• Action Taken with Study Treatment
• Age Units
• Country
• Domain Abbreviation
• Ethnicity
• Dose Form
• Identification variable
• Category for Inclusion/Exclusion
• Not Done or Null Answer
• No / Yes/ Unknown Answers

• Outcome of Event
• Race (deferred)
• Reason for Non-Completion
• Causality
• Route of Administration
• Severity / Intensity
• Sex
• Size Code
• System Organ Class
• Relation to Reference Period
• Age Group

• Type of Control
• Description of Trial Design
• Diagnosis Group
• Trial Indication Type
• Trial Blinding Schema
• Standard Toxicity Grade
• Trial Phase
• Trial Summary Parameter 
• Type of Trial
• Vital Signs Test Name
• Units for Vital Signs

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SDTM Package 2A / 2B Terminology
Interventions
Findings
Events
Exposure
Labs
InclExcl
AE
ConMeds
Vitals
SubjChar
Disp.
Subst Use
ECG
PhysExam
MedHist
PG
QS
MB
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NCI EVS Partnership
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Core Working Principals(CDISC Terminology
Program)

• Evaluate and/or utilize existing terminology 1st
• Expand existing vocabularies where incomplete,
  working with vocabulary developer / owner
• Harmonize across CDISC Models and with
  pre-existing vocabulary initiatives
• Ensure terminology recommendations suit
  international needs for global organizations and
  projects
• Ensure a sustainable open source environment
  and infrastructure for production terminology
  supporting terminology evolution

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Collaboration with NCI EVS

• NCI Enterprise Vocabulary Services (EVS) has
  committed expertise and significant resources in
  support of the CDISC Terminology Initiative and
  FDA Vocabulary Initiatives such as SPL, ICSR,
  RPS, CDRH Healthcare Devices, etc

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Once upon a time
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CDISC-NCI EVS Collaboration
NCI EVS
Production Representations

• Definition developed
• Concept assigned
• Harmonized with related work (FDA)
• Mapped to other CT

EVS Report Writer (via .ftp website) CDISC/FDA
Subset files, posted monthly EVS Term. Browser
caDSR CDE Browser?
CDISC Codelists in Excel (Terms only)
NCI EVS NCI Enterprise Vocabulary Services
caDSR Cancer Data Standards Repository
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Production Environment

• NCI EVS Vocabulary Products
• Authoritative source for CDISC Terminology
• NCI Thesaurus federal standard controlled
  terminology with definitions
• NCI Metathesaurus maps various vocabularies
  (50)
• Terminology Report Writer rapid access and
  retrieval of core terminology sets (CDISC, FDA)
• Terminology Browser search for, preview and
  download terminology and associated relationships
  
• NCI caDSR Tools (evaluated)
• Create common data elements (CDEs) from
  foundational terminology in EVS
• CDE Browser search for and download data
  elements

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Terminology Developmenttoday(fully integrated
processes)
Stage I Standard Definition/Team Initiation
Stage II (a-e) Standards Development/Review/V
1.0 Release

• Initial terminology, code list and definition
  development (Excel)
• Analyze, compare and harmonize with existing EVS
  terms (NCI Thesaurus)
• Standards Review (CDISC Internal Public
  Review) / Vet Comments
• Finalize terminology set and load into EVS (NCI
  Thesaurus)
• Put terminology in production via .ftp site and
  NCI Terminology Browser
• Assess need for other representations such as
  caDSR (SDTM P-1)

Stage III Education Support
Stage IV Updates Maintenance
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Standard Controlled Terminology
Global Pharma CROs
FDA Academia
International SDOs
Vocabulary Developers
Health Level Seven (RCRIM TC)
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The Home Stretch
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Global Terminology

• Terminology Development
• Terminology Publication

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2007 Terminology Priorities

• Finalize production release of Labtest, SDTM
  Package 2A and SDTM Package 2B term sets
• Harmonize with and support new global terminology
  projects such as those initiated by ISO, ICH
  WHO
• Scope, support and harmonize with other priority
  projects CDASH, SEND, BRIDG and beyond
• Develop user guidelines for production
  terminology access, download and implementation
• Support other projects related to development of
  global therapeutic data standards (e.g.
  Tuberculosis, Cardiology)
• Further develop terminology education and
  training, including workshops and online tutorials

CDASH Clinical Data Acquisition
Standards Harmonization BRIDG
Biomedical Research Integrated Domain Group
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Special Thanks to

• Andreas Gromen (Schering AG, Germany)
• Margaret Haber (NCI EVS)
• Mary Lenzen (Octagon Research)
• CDISC Terminology Team Volunteers

CDISC is now in Controlof its terminology
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• Knowing is not enough
• we must apply.
• Willing is not enough
• we must do.
• - Goethe-

If you are interested in contributing to the
CDISC Terminology Initiative, please contact me
Bron W. Kisler [phone] bkisler_at_cdisc.org