Le point sur les activités du
CDISC
9 juin 2004
Pierre -Yves Lastic
Sanofi -Synthélabo
Data
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CDISC Update ?CDISC Standards Overview
?CDISC 2003 Achievements
?CDISC 2004
–Objectives
–CDISC / HL7 Collaboration
–Standards Harmonization using HL7
Methodology
–Single Source Project
–SDS v 3.1
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Data Sources ?Site CRFs ?Laboratories ?Contract Research Organizations ?Development Partners Operational Database ?Study Data ?Audit Trail ?Metadata Operational Data Interchange & Archive:ODM, LAB Submission Data ?CRT/Domain Datasets ?Analysis Datasets ?Metadata Submission Data Interchange & Archive:SDS, ADaM CDISC Standards: Overview ODM = Operational Data Model/Std SDS = Submission Domain Standards LAB = Laboratory Data Model/Std ADaM = Analysis Data Models Future Uniform Standard Data
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Protocol Std
Clinical Document
Architecture
DICOM
ADaM CDISC in the “World of Standards” 2003International Conference on Harmonization (ICH)U.S. Dept. of Health and Human Services
(HHS)Health Level 7 (HL7)U.S. FDA CDISC TC:RCRIM NIH/NCI NLM
EFPIA EMEA MHLW
KIKO PhRMA JPMA CDC Reference
Information Model
RIM LAB eCTD LOINC
ISO
SNOMED
MedDRA ODM SDS = Organization = Dictionary,
Codelist = Standard = Model = Document Standard,
or Architecture
Data
Management 2003 Progress on CDISC Standards
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B
Biomédical ?LAB Standard: Production Version 1.0.1
available; approved HL7 RIM message
–V1.0 plus microbiology extension
–Four methods of implementation
?ODM Standard: Production Version 1.2
available as an XML schema
–Define.xml in progress with SDS metadata
?SDS Standard: Version 3.0 available
–Successful FDA Pilot closed in October 2003
–Version 3.1 anticipated to be HL7 Informative
Document referenced by FDA Guidance by Q2 2004?ADaM: Selected analysis dataset models
Data
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M CDISC Strategic Goals 2004
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Biomédical ?Standards Adoption by Industry and Regulatory Authorities
?Evaluation and Selection of Means to Maintain CDISC Standards
?Development and Maintenance of Strategic Relationships/Alliances
?Explore Priorities and Feasibility of Developing Standards for Unmet Needs
?Expand Funding and Ensure Efficient and Effective Processes
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Standards Adoption ?Full FDA Support for CDISC SDS: Version 3.1 already accepted by FDA as submission
standard, plan to require it thru future CFR rule
?EMEA joined Protocol Representation Project,
plan to use for future EUDRACT & eCTD
developments
?All major Pharma Companies, CROs & Software
vendors are CDISC sponsors & members
… BUT…
?…increasing pressure for Harmonization within
CDISC and with HL7 Standards (eg Letter from
NCI to CDISC Board of Directors in January
2004)
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Collaboration of
CDISC with Health Level Seven
(HL7)
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?The world’s leading standard for the electronic interchange of healthcare information
–>20 Global affiliates
–16 years of operation
?American National Standards Institute (ANSI)-accredited Standards Development Organization (SDO);also, ISO standards
?Acknowledged by the Department of Health and Human Services (HHS) as the standard for healthcare information exchange
Health Level Seven (HL7)Data
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Initiated as Clinical Trials SIG in Jan 2001
RCRIM TC approved in April 2002
Joint Leadership: HL7, CDISC,FDA Active Membership:
FDA , CDISC,HL7 & others
?Develops common standards for clinical research and regulatory
evaluation
?Assures that other HL7 standards (healthcare standards) can be used
in regulated clinical research
?Co-chaired by FDA (R. Levin), HL7/Pharma (L. Quade) and CDISC
(B. Tardiff)
HL7 Regulated Clinical Research and Information Management (RCRIM) Technical Committee Patient Safety SIG Genomics SIG
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Biomédical RCRIM: Current Initiatives
Research Process !Standardized
representation of clinical trial protocol
Research Data
!Periodic reporting of clinical
trial laboratory data (LAB)
!Annotation of ECGs
!Clinical trial data for regulatory
submission (SDS)
!Define.xml (ODM)
!Non-clinical data for regulatory
submissions (SEND)
Surveillance
Individual Patient Safety
Reports (eMedWatch)
Regulatory Information
Structured Product label
eStability data
HL7 Ballots
Approved
!Direct CDISC Involvement
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Biomédical Standards Harmonization
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CDISC Standards Harmonization: Background (1)?Different models developped for different
clients:
–SDM / SDS => FDA
–ODM => Software providers (eCRF) &
Sponsors / CROS
–LAB => Central Labs / Sponsors
–ADaM => Statisticians
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CDISC Standards Harmonization: Background (2)?Different focus:
–ODM/LAB: data exchange and archiving
–SDS/ADaM: data storage for analysis &
reporting
?Different languages
–ODM: XML
–LAB: ASCII, SAS XML
–SDS/ADaM: SAS
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CDISC Standards Harmonization: Background (3)?Separate development lead to diverging
standards
?CDISC Technical Coordination Committee
created, but couldn’t fix all issues
?Increasing need & pressure from users(*)
to harmonize CDISC models within each
others and with HL7
(*) Letter from NCI early 2004
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B Biomédical ODM Operational Data Model ?XML format for clinical study data and metadata ?Supports regulatory-compliant e-Archive format SDS
Submission Data Standards
*Describes content, structure and attributes of
data for regulatory submissions
*Defines metadata content for standard domains
*Facilitates regulatory reviews LAB
Laboratory Data Model
?Defines standard content for transferring clinical laboratory data from Labs to sponsors ?ASCII, SAS, XML, and
HL7 implementations available
ADaM Analysis Dataset Models ?Provides models for commonly used statistical analyses .
Operational Data Modeling Submission Data Modeling ODM values can be expressed via SDS metadata Data Sources Regulatory Reviewers
LAB data can be mapped into ODM XML Applies submission model for
analysis datasets
ODM can be used to represent and archive submission data
Data
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CDISC and RCRIM Standards (Collaborative Groups ~ FDA, CDISC, HL7, SEND, CDC, NIH, LOINC, etc.)ADaM Protocol
Elements LAB SDS ODM HL7 Reference
Information Model
RIM Patient
Safety Report Product Label eStability
Data
CDA CDISC FDA
R egulated C linical R esearch
In formation
M anagement Technical Committee ECG SEND Non-Clin
SDS V3RIM Inf.Doc Collaborative Groups
Inf.Doc
Inf.Doc HL7RCRIM TC Inf.Doc Define.xml
V3RIM CDA
V3RIM V3
RIM
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Laying the Groundwork: Some Definitions ?Syntax vs Semantics
?Interchange vs Interoperability
?Complexity and Complex Systems
?Architecture and Software Engineering
?Process vs Implementation
?Information Model vs Data Model
Data
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M Definitions (cont)
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Biomédical ?The Communications Pyramid
–Problem vs Solution
–Analysis vs Design
?Models and Modeling Languages
–The Unified Modeling Language (UML)
?The HL7 Development Framework (HDF)?HL7 Version 3
?Clinical Document Architecture (CDA)
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Syntax vs Semantics
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Biomédical ?Time flies like an arrow.
?Fruit flies like a banana.
?The dog eats red meat.
?The dog eats blue trees.
?Give the patient pain medication.
?Give the patient medication for pain.
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Syntax vs Semantics ?Syntax (structure)
–Claims forms –HTML ?Semantics (meaning)–ICD, MedDRA, SNOMED
?Standardization process requires
oversight...
–ANSI / ISO (formal)–W3C
(de facto oversight)
“The great thing about standards is
that there are so many to choose
from.”
---anonymous
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Interoperability ?interoperability
:ability of two or more systems or
components to exchange information and to
use the information that has been
exchanged.
Source: IEEE Standard Computer Dictionary: A Compilation of
IEEE Standard Computer Glossaries, IEEE, 1990]
Semantic
interoperability
Syntactic interoperability
Data
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B Interchange vs Interoperability
Biomédical ?Interchange
–Syntactic interoperability
?Interoperability
–Semantic interoperability
?Prerequisites for semantic interoperability –Robust data type specification
–Ability to utilize controlled terminologies
Data
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?HL7 Mission Statement: “Develop standards for that support interoperability in healthcare, i.e. “machines operating in the healthcare space will understand the structure and meaning of the information exchanged or processed using HL7 Specifications.”
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Interchange vs Interoperability ?CDISC Mission Statement: “Develop
worldwide industry standards to support
the electronic acquisition, exchange,
submissions, and archiving of clinical trial
data and metadata for medical and
biopharmaceutical product development.”
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The Pillars of Interoperability Necessary but not necessarily sufficient ?Common model across all domains on
interest
?Foundation of rigorously defined data
types
?Methodology for interfacing with controlled
vocabularies
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Complexity and Complex Systems ?“Multiple vertical levels of organization with
processes that cross horizontal
organizational boundaries.”
UCSF School of Nursing 28
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!A simple business produces a single
product via a single business
process.
Produce a Product
A Simple Business
A Simple System
UCSF School of Nursing 29
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!An evolving business
produces multiple related
products via several related business
processes.Manage Product
Production
An Evolving Business
Produce Product A Produce Product B
An Evolving System Data
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Manage Divisions
A Complex Business
Manage Unit A Manage Unit B
Produce Product A Produce Product B
"The complex business
produces multiple related
products via several related business processes.
"Multi-level hierarchical
organization
"Business processes cross functional boundaries
A Complex System
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Providers
Payors Case
Managers Customer
Healthcare Information Flow Data
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Providers
Payors Case
Managers Customer
Healthcare Information Flow
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The Conclusion Healthcare is a
Complex
Business System!
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(Complex)Business System “Facts of Life” ?Many processes cross functional boundaries ?Many products of value have multiple
stakeholders with conflicting agendas
?The result is often….
–Duplication of effort
?Redundant data
–Inconsistency and Variability
?Lack of semantic interoperability
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?A house for your dog
?A shack for yourself
?A single-family home for your family ?A skyscraper for your customers ?Considerations drive Complexity –Uses
–Users “The collection of objects, relationships, behaviors, and interactions that define a system.”
“Systems succeed for a variety of reasons.
They fail for one: lack of architecture.”
---Grady Booch
Architecture:An Discipline for Managing Complexity Data
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?The critical elements
–Structural Walls
–Partition Walls
–Furniture
?Architectural planning focuses on defining the structural walls and engineering for the Partition Walls
–“We cannot prevent change…rather, we should expect change and engineer systems to change with minimal cost and disruption.” UML Reference Guide
Architecture:An Discipline for Managing Complexity
Data
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The Communication Pyramid:Communicating complexity is HARD ?The Problem Space
–“What”
–Discovered through Analysis
?The Solution Space
–“How”
–Discovered through Design
–One Problem #Many Solutions
Data
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The Communication Pyramid:Communicating complexity is HARD ?Technologists often begin building the
Solution before understanding the Problem
–“The Problem can’t be understood until a
Solution is built!”(the SE conundrum)
–Resolution/management of this apparent
contradiction requires good application of
Software Engineering Best Practices
Data
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Process vs Implementation ?Process
–Communicate a message to Mike
?Implementation
–In-person
–Phone call
–Voicemail
?In healthcare, paper is the implementation,
not the process
To effectively change the process, you must understand it.
To understand it, you must first separate it from its various
implementations.
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Process vs Implementation:Atoms vs Bits Healthcare professionals have been bound to
paper for so long that they often confuse the
mechanics of paper-based data collection,
processing, archiving, etc. as the process rather
than the implementation. (“Using atoms to move
bits.”)