Title: The BRIDG Project: A Model to Support Interoperability in Clinical Research
1The BRIDG Project A Model to Support
Interoperability in Clinical Research
You cant build a skyscraper by nailing together
10,000 dog houses . Grady Booch
- Douglas B Fridsma, MD PhD
- Department of Biomedical Informatics
- University of Pittsburgh
2Talk Organization
- Why do we need models like BRIDG?
- What is the BRIDG project?
- What have we learned?
- Does it work?
- Current status
3Managing the Processes of Clinical Trials
Modern clinical research requires complex,
interconnected systems
- Clinical and translational research is a complex
systems of organizations, people and information
systems that require detailed descriptions of - definitions of data (what)
- the process of care (how)
- so that differences in outcomes can be analyzed
and compared
4Modern clinical research requires complex,
interconnected systems
- But clinical and translational data must be able
to interoperate with the larger research
enterprise - Other applications
- Other systems
- Other departments
- Standardization and the ability to hand off
data and research results is critical to
innovation
5Modern clinical research requires complex,
interconnected systems
Ultimately, successful translational research
requires complex connections to exchange
information within and between organizations
6What are we trying to do?
- To define implementation-independent domain
semantics (define the what and the how of
clinical research) - To uncover the myriad of semantic ambiguities
present in the complex domain of clinical
research - To build a foundation for achieving computable
semantic interoperability - The key to data integration
7Interoperability
- The ability of multiple systems to exchange
information and to be able to use the
information that has been exchanged.
Datatypes Common data elements
8Talk Organization
- Why do we need models like BRIDG?
- What is the BRIDG project?
- What have we learned?
- Does it work?
- Current status
9What is BRIDG?Biomedical Research Integrated
Domain Group
- A model of the shared semantics of regulated
clinical research - A communication bridge between
- clinical research domain experts and technical
experts - different models of clinical research information
(EPOCH-BRIDG) - An open community of stakeholders interested in
developing standards for exchanging information
about clinical research - HL7, NCI, CDISC, FDA, ITN
- The semantic foundation for application and
message development in HL7, caBIG, and CDISC - A foundation for research in knowledge
representation and semantic interoperability
10What is BRIDG?Biomedical Research Integrated
Domain Group
- A model of the shared semantics of regulated
clinical research
11So how did BRIDG get started?
- Two important streams of development that have
been brought together into a collaborative
framework - CDISC 2003, started constructing an analysis
model to map ODM standards to HL7 - NCI 2004, started caBIG initiative to construct
a structured protocol representation and
interoperability among clinical research in
cancer
12Desiderata
- Did not want to construct Yet another standard
- The good thing about standards is there are so
many to choose from - Open-source
- Modeled processes and organization after other
successful open-source projects - Mozilla, Firefox, Linux, etc
- Model is small groups (Technical Harmonization
Committee), vet in large groups (Advisory Board) - Provide a mechanism to scale the development work
- Parallelize the development
- Prevent collaborators from colliding with each
other - Allow us to modeling in the open
- In the BRIDG project, we have tried to
operationalize the collaborative models required
for roadmap initiatives
13Current Classes in Core Elements
14What is BRIDG?Biomedical Research Integrated
Domain Group
- A model of the shared semantics of regulated
clinical research - A communication bridge between
- clinical research domain experts and technical
experts - different models of clinical research information
(EPOCH-BRIDG)
15What Problem(s) Does BRIDG Solve?
- The Communications conundrum
- Experts know about the how to do clinical
research but dont understand how to build
software - Technologists understand how to build software
but dont understand the intricacies of the
clinical environments and clinical research - Any implementation (i.e. solution) is a
compromise of the original problem statement - Compromises must be chosen wisely
- should be based on a deep understanding of the
problem and a dialogue between Problem Space and
Solution Space Experts
16The Communication Pyramid
Standardized Models (UML)
Non-standard Graphics
ad hoc Drawings
Problem Space
Solution Space
Implementation-Independent
Abstraction
Implementation-Specific
Structured Documents
Free-text Documents
Discussions
Communication
17What is BRIDG?Biomedical Research Integrated
Domain Group
- A model of the shared semantics of regulated
clinical research - A communication bridge between
- clinical research domain experts and technical
experts - different models of clinical research information
(EPOCH-BRIDG) - An open community of stakeholders interested in
developing standards for exchanging information
about clinical research - HL7, NCI, CDISC, FDA, ITN
18Current Collaborators
- HL7
- Official domain analysis model for the HL7 RCRIM
technical committee - All HL7 messages must be able to demonstrate
bi-directional semantic traceability before
they can be balloted - CDISC
- The integrative model for all current CDISC
standards
19Current Collaborators
- FDA
- Developing an HL7 message based on CDISC SDTM in
with the RFA requires capturing the semantics in
BRIDG - Regulated Product Submission (RPS) is the next
HL7/FDA message to use BRIDG - Immune Tolerance Network (ITN)
- Using BRIDG to integrate open-source caBIG tools
with existing MDA applications
- caBIG
- Utilized as framework for NCIs caBIG (standard
within CTMS WS) - Additional non-CTMS semantics (e.g. FireBird,
CDUS, etc.) being incorporated
20What is BRIDG?Biomedical Research Integrated
Domain Group
- A model of the shared semantics of regulated
clinical research - A communication bridge between
- clinical research domain experts and technical
experts - different models of clinical research information
(EPOCH-BRIDG) - An open community of stakeholders interested in
developing standards for exchanging information
about clinical research - HL7, NCI, CDISC, FDA, ITN
- The semantic foundation for application and
message development in HL7, caBIG, and CDISC
21Achieving interoperability from a common semantic
foundation
IMPLEMENTATION SOLUTIONS
STAKEHOLDERS
22What is BRIDG?Biomedical Research Integrated
Domain Group
- A model of the shared semantics of regulated
clinical research - A communication bridge between
- clinical research domain experts and technical
experts - different models of clinical research information
(EPOCH-BRIDG) - An open community of stakeholders interested in
developing standards for exchanging information
about clinical research - HL7, NCI, CDISC, FDA, ITN
- The semantic foundation for application and
message development in HL7, caBIG, and CDISC - A foundation for research in knowledge
representation and semantic interoperability
23Pilot Study mapping BRIDG to EPOCH
- BRIDG
- HL7, caBIG, CDISC stakeholders
- Developed collaboratively with stakeholders
- shared domain model for protocol-driven clinical
research - Comprehensive
- Consensus-based
- Abstract and context neutral
- EPOCH
- Immune Tolerance Network (ITN)
- International collaborative research effort that
sponsors clinical trials and mechanistic assays
on immune tolerance - EPOCH clinical trial model
- Developed at Stanford Medical Informatics
- Designed to provide semantic foundation for
management of clinical trials
24Approach taken to mapping between EPOCH and BRIDG
- Semantic alignment
- Overcoming representation language mismatch
- Overcoming representation choice mismatches
- Principal team members
- Douglas Fridsma (Pitt)
- Webster Kelsey (Pitt)
- Samson Tu (Stanford)
- Ravi Shankar (Stanford)
- Dave Parrish (ITN)
25Approach taken
- Semantic alignment
- Use Excel spreadsheet to systematically review
and document possible mappings - Define necessary preconditions for mapping
- Overcoming representation language mismatch
- Overcoming representation choice mismatches
26Semantic Alignment Excel spreadsheet
27Semantic Alignment Restrictions on EPOCH
- Mapping from EPOCH to BRDG gt Place restrictions
on EPOCH - Only one schedule of activities
- Period has no subperiods
- Limited temporal annotations
28Approach taken
- Semantic alignment
- Overcoming representation language mismatch
- Overcoming representation choice mismatches
29Overcoming representation language mismatch
BRIDG-in-OWL
Scope BRIDG Study Planned View BRIDG Complex
Data Types
30Approach taken
- Semantic alignment
- Overcoming representation language mismatch
- Overcoming representation choice mismatches
31Overcoming representation choice mismatch Epoch
example
EPOCH
Period
Arm1Cycle1
Arm1Cycle2
PeriodTypeIntervention
PeriodTypeIntervention
Screening0
Arm2Cycle1
Arm2Cycle2
PeriodTypeScreening
PeriodTypeIntervention
PeriodTypeIntervention
BRIDG
Intervention epoch
Screening epoch
32SWRL rule to map epochs
- EPOCHperiodTypes of periods correspond to
BRIDGepochs - EPOCH periodType.label corresponds to
BRIDGepoch.code.displayName
33Successfully used an EPOCH clinical trial to
configure BRIDG Patient Study Calendar application
SWRL rules
SWRL rules
Patient Study Calendar
Herold protocol in EPOCH
Herold protocol in BRIDG
Herold protocol in PSC XML
- Automated mappings except for one relationship
- Because of OWL/SWRLs open-world assumption,
First epoch cannot be derived as an epoch that
has no predecessor
34Pilot conclusions
- Semantic interoperability requires
- Harmonization of subsets of ontologies/models
- Overcoming mismatches in representation languages
and representation choices - OWL restrictions and SWRL rules help to overcome
semantic and syntactic mismatches - Possible future work
- Continued harmonization of BRIDG/EPOCH
- Scalability and (semi-)automation of method
35Talk Organization
- Why do we need models like BRIDG?
- What is the BRIDG project?
- What have we learned?
- Does it work?
- Current status
36Lessons learned (so far) in the BRIDG project
- Scope keep it clear and focused (ie, solve a
problem that exists) and standardize to the
extend needed - Keep the model generic, faithful, free of
implementation-specific formalisms, and
supporting the requirements - Refine through experience, and not endless
discussions
37Scope of BRIDG
- The domain of the regulated clinical research
information management technical committee in
HL7 - Protocol-Driven Research with human, animal or
device subjects, plus appropriate associated
regulatory documentation. - Analysis-level semantics
- Business processes
- Static structures
- Use-case driven
- in-scope and out-of-scope determined by the
use-case - Does not include vocabulary or terminology
choices - BRIDGCodedConcept Datatype links to other
places where domain semantics can be
represented - Area of active research in understanding how
ontologies and information models link to
vocabularies and terminologies
38Lessons learned (so far) in the BRIDG project
- Scope keep it clear and focused (ie, solve a
problem that exists) and standardize to the
extend needed - Keep the model generic, faithful, free of
implementation-specific formalisms, and
supporting the requirements - Refine through experience, and not endless
discussions. - Understand the difference between consensus,
abstraction, and harmonization
39The difference between Consensus, Abstraction and
Harmonization
- Consensus
- Consensus statements often achieve agreement
through being ambiguous - United Nations, guideline consensus statements
- Abstraction
- generalized models that are useful for a broad
range of different domains (HL7 RIM) - definitions are abstract, domain independent
(although specific to an implementation) and more
helpful for implementation than they are for
domain experts - Harmonization
- Creating definitions that all experts agree on,
creating distinctions between concepts to clarify
the semantics when they dont agree, and
imbedding those semantics in the business
processes
40Harmonize Concepts, Not Words
Symbol Protocol
Source John Speakman
41Lessons learned (so far) in the BRIDG project
- Scope keep it clear and focused (ie, solve a
problem that exists) and standardize to the
extend needed - Keep the model generic, faithful, free of
implementation-specific formalisms, and
supporting the requirements - Refine through experience, and not endless
discussions. - Understand the difference between consensus,
abstraction, and harmonization. - Models are only a piece of the puzzle
- Datatypes, vocabularies and terminologies provide
additional clarification of the semantics
42BRIDG is only one piece of the semantic puzzle
- Common model across all domains-of-interest
- The representation of clinical trials in BRIDG
- Model grounded on robust data type specification
- Common data elements (ISO 11179) in the cancer
Data Standards Repository (caDSR) - Methodology for binding terms from concept-based
terminologies - UML loader, semantic connector, Enterprise
Vocabulary Server, LexGRID etc - A formally defined process for defining specific
structures to be exchanged between machines, i.e.
a messaging standard - HL7 and implementation specifications
- caBIG unified process/model driven architecture
43Lessons learned (so far) in the BRIDG project
- Scope keep it clear and focused (ie, solve a
problem that exists) and standardize to the
extend needed - Keep the model generic, faithful, free of
implementation-specific formalisms, and
supporting the requirements - Refine through experience, and not endless
discussions. - Understand the difference between consensus,
abstraction, and harmonization. - Models are only a piece of the puzzle
- Datatypes, vocabularies and terminologies provide
additional clarification of the semantics - Use a larger development framework to organize,
iterate, and trace the semantics - Provides a mechanism to integrate multiple
projects, manage change
44Translational Research is a Cycle
Support for Research Protocol
Development
Support for CT Enrollment Management
ResearchDevelopment
Pre-Trial Setup
PatientEnrollment
New IdeaGeneration
DataAnalysis
PatientManagement
Reporting Administration
Financial Billing
Support for Data Mining Analysis
Support for CT Reporting Administration
45The Unified Process(Iterative/Incremental,
Risk-Focused, Architecture-Centric)
46In BRIDG Process Matters
- Modeled on open-source software development
initiatives - Scalable processes to support coordination and
collaboration across multiple modeling groups - Organizational structure with stakeholder
representation - Focus on semantics, not representation or
implementation allows for variation around a
common model
47Lessons learned (so far) in the BRIDG project
- Scope keep it clear and focused (ie, solve a
problem that exists) and standardize to the
extend needed - Keep the model generic, faithful, free of
implementation-specific formalisms, and
supporting the requirements - Refine through experience, and not endless
discussions. - Understand the difference between consensus,
abstraction, and harmonization. - Models are only a piece of the puzzle
- Datatypes, vocabularies and terminologies provide
additional clarification of the semantics - Use a larger development framework to organize,
iterate, and trace the semantics - Provides a mechanism to integrate multiple
projects, manage change - The importance of capturing dynamic semantics
(activities) of clinical trials research - Clarifies the data and concept definitions
- Provides the context for use of the data
structures - Sets the stage for a service-oriented architecture
48Work Process Information in BRIDG
- Activity Diagrams
- Captures the workflow of clinical trials research
- Provides the context for when (and how) data is
exchanged - Helps to clarify the definitions (the what) by
describing how the data is used
49Mapping the Clinical Research Domain
50Talk Organization
- Why do we need models like BRIDG?
- What is the BRIDG project?
- What have we learned?
- Does it work?
- Current status
51Recent Experience With BRIDGThe CTMS WS
Interoperability Project (1)
- Goal In 9 weeks (including Holidays), build
interoperable support for three Use Cases across
five applications in the Clinical Trial
Management System (CTMS) Work Space - Use Cases to be defined by group of SMEs as pain
points - Applications include
- Patient Study Calendar
- Static model has been harmonized with BRIDG
- Lab Hub
- Static model has been harmonized with BRIDG
- Adverse Event Reporting System
- Application development began concurrent with
Interoperability Project - Early analysis work already done and compliant
with BRIDG - Patient/Clinical Trial Registry
- Repository of links between patients and trials
- COT CTDMS (Oracle Clinical)
- Trial repository export capability only
Source Charlie Mead
52Recent Experience With BRIDGThe CTMS WS
Interoperability Project (2)
- Process Iterative/Incremental SEP utilizing
BRIDG as DAM - Two one-month iterations
- Limited ability to change existing code base
- Process began with Business Modeling
- Activity Diagrams for each Use Case mapped to
BRIDG - BRIDG Extract generated based on AD ? BRIDG
mapping - BRIDG Extract ? XMI ? analysis-level XSD ?
implementation-level XSM (common wire format) - short time-line ? no formal messaging
structures (V3 messages will be developed at a
future date) - The Conclusion The project could not have
succeed without the use of a DAM - The previous harmonization/common application of
BRIDG by 3/5 of the applications (and the ability
of the other 2 applications to map appropriate
static structures to BRIDG) enabled the project
to succeed
Source Charlie Mead
53Talk Organization
- Why do we need models like BRIDG?
- What is the BRIDG project?
- What have we learned?
- Does it work?
- Current status
54What have we accomplished?
- BRIDG is no longer a modeling exercise, but a
robust model used by - the National Cancer Institute for all application
development - Commercial clinical trials software developers
- CDISC to unify their existing models
- HL7 for all HL7 messages related to clinical
trials research - FDA for electronic data submission standards
- Other collaborators (immune tolerance network) to
integrate applications and clinical trials work
processes - BRIDG release V1 June, 2007
- In the process we have
- Developed generalizable scaleable processes to
support collaboration across organizations,
models, and domains - Begun to understand how to overcoming semantic
and representational differences between
different ontologies and terminologies
55Value of analysis modeling for semantic
interoperability
- If you understand
- The processes (activities) that you do within
your organization to support clinical and
translational research - The information (data) that you use for these
activities - You can
- Reduce redundancy in your organization
- Redesign organizational processes
- Know what to share (and what not to)
- Integrate custom and commercial applications (you
know where they fit in your organizational
activities and data) - Create a shared understanding of the work of
clinical trials research (facilitates culture
change) - This becomes critical for any program in which
you want to - Exchange data between different disciplines
(translational research) - Clinical trials and translational programs (CTSA)
56Acknowledgements leadership
- Leadership and collaboration
- CDISC board members
- Becky Kush, CDISC
- Ken Buetow, Peter Covitz, Sue Dubman, Christo
Andonyadis, John Speakman, NCI - Charlie Mead, HL7, BAH
- Barbara Tardiff, Linda Quade, Ed Trip, Ed Helton,
Randy Levin (FDA), RCRIM technical committee of
HL7
57AcknowledgementsOrganizations
- Technology companies
- ScenPro
- IBM
- SAS
- Fast track
- SAIC
- BAH
- Oracle
- Pharmaceutical companies
- AstraZeneca
- Boehringer-Ingelheim
- Eli Lilly
- GlaxoSmithKline
- Merck
- Novartis
- Pfizer
- Sanofi-Aventis
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60www.BRIDGproject.org
- Fridsma_at_cbmi.pitt.edu
- The Technical Harmonization Committee
- Smita Hastak, ScenPro
- Julie Evans, CDISC
- Charlie Mead, BAH
- Douglas Fridsma, University of Pittsburgh