BRIDG Model: A Comprehensive Information Model for Biomedical Research

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BRIDG Model A Comprehensive Information Model
for Biomedical Research
25-April-2006 Douglas B. Fridsma University of
Pittsburgh School of Medicine Julie EvansCDISC
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CDISC Mission

• 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.

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Future of CDISC Models
Future Uniform CDISC Standard Harmonized with
HL7
Operational Data Interchange Archive ODM, LAB
Submission Data Interchange
Archive SDTM, SEND, ADaM

• Data Sources
• Site CRFs
• Laboratories
• Contract
• Research
• Organizations
• Development
• Partners

• Operational
• Database
• Study Data
• Audit Trail
• Metadata

• Submission
• Data
• CRT/Domain Datasets
• Analysis Datasets
• Metadata

Protocol
ODM Operational Data Model SDS
Submission Domain Standards LAB Laboratory
Data Model ADaM Analysis
Dataset Models SEND Std. Exchg.
Non-clinical Data Standard Protocol
Representation and Terminology
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How does BRIDG support these goals?

• CDISC started constructing an analysis model in
  2003 to clarify semantic interoperability among
  CDISC models, and between the CDISC models and
  HL7
• BRIDG has become a collaborative mechanism with
  other people interested in developing standards
• HL7 is using it as the basis for HL7 messages in
  RCRIM
• NCI is using it to develop interoperable
  applications to support cancer research
• Technology providers are using it to develop
  standards-based applications
• CDISC continues to use it to clarify the
  semantics of the existing CDISC models
• BRIDG has provided a way for CDISC standards to
  gain visibility among standards, research, and
  technology organizations

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CDISC Roadmap Timeline
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CDISC Standards Harmonization
Operational Data Interchange Archive ODM, LAB
Submission Data Interchange Archive SDS,
ADaM SEND

• Data Sources
• Site CRFs
• Laboratories
• Contract
• Research
• Organizations
• Development
• Partners

• Operational
• Database
• Study Data
• Audit Trail
• Metadata

• Submission
• Data
• CRT/Domain Datasets
• Analysis Datasets
• Metadata

BRIDG Harmonizing to THE CDISC Standard
Protocol
ODM Operational Data Model/Std SDS
Submission Domain Standards LAB Laboratory
Data Model/Std ADaM Analysis Data
Models SEND Standards for the Exchange of
Non-Clinical Data
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Why BRIDG?
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Interchange vs Interoperability
Syntax ? StructureSemantics ? Meaning

• Main Entry interoperability ability of
  a system ... to use the parts or equipment of
  another system Source Merriam-Webster web site
• interoperability ability of two or more
  systems or components toexchange information and
  to predictably use the information that has been
  exchanged.
• Source IEEE Standard Computer Dictionary A
  Compilation of IEEE Standard Computer
  Glossaries, IEEE, 1990

Semanticinteroperability
Syntacticinteroperability (interchange)
Source Charles Mead, MD, HL7
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Computerized doesnt mean syntactic
interoperability
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1
5
2
3
4
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Semantic interoperability Protocol and the
Semiotic Triangle
Symbol Protocol
Source John Speakman/Charlie Mead
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Semantic Interoperability

• To understand the data being received you must
  know both
• The definition of each element of data, and its
  relationship with each of the other elements
• you must have a semantic model of the data and
• The terminology to be used to represent coded
  elements, including the definitions, and
  relationships within the terminology

Source HL7
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The Pillars of (Semantic) InteroperabilityNecessa
ry but not Sufficient

• 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
• Enterprise Vocabulary Server, terminologies
• A formally defined process for defining specific
  structures to be exchanged between machines, i.e.
  a messaging standard
• HL7 and implementation specifications
• CDISC standards development process
• caBIG unified process/model driven architecture

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What is BRIDG?

• A formal model of the shared semantics of
  regulated clinical trials research
• A communication bridge between
• clinical trial domain experts and technical
  experts
• different models of clinical trials information
• An open community of stakeholders interested in
  developing standards for exchanging information
  about clinical trials
• HL7 Domain analysis model in Regulated Clinical
  Research (RCRIM) technical committee
• caBIG analysis model for model-driven development
• CDISC integrating model for current standards
• The semantic foundation for application and
  message development in HL7, caBIG, and CDISC

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So 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 trials research
  in cancer

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Model History the CDISC work

• Fall 2003 CDISC board meeting recognized
  that integration of their standards required an
  comprehensive model of clinical trials
• Jan 2004 CDISC begins work on integrated domain
  analysis model
• Mar 2004 First modeling session in Philadelphia
• Summer 2004 Multiple modeling sessions to
  expand the model
• Presentation to HL7 RCRIM, Fall 2004

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caBIG and the Development of Structured Protocol
Representation

• Spring 2004 kick-off of the caBIG project
• University of Pittsburgh award the contract to
  develop a structured protocol representation to
  support clinical trials

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Merging the caBIG and CDISC projects

• Fall 2004 caBIG identified best of breed
  models in the CDISC standards and HL7 messages
• November 2004 First joint CDISC/HL7/caBIG
  modeling session
• Between November 2004 and March 2005 multiple
  modeling sessions to develop the scaffolding of
  the domain analysis model (SPR). Renamed BRIDG to
  reflect the shared interests of all stakeholders
• March 2005 to now
• Development of the dynamic aspects of the model
• Develop scalable processes to support
  collaboration and expansion of the model, based
  on software best practices
• Initiation of 8 subdomain projects within BRIDG

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Current Organization of the BRIDG project
HL7
FDA

• BRIDG Advisory Board
• Representation from the current stakeholders
• Help to allocate priorities and identify
  resources
• Assist with vetting the model in the various
  constituents
• Technical Harmonization Group
• Responsible for ongoing model maintenance
• Developing shared harmonization processes
• Multiple subdomain projects
• Representation from pharmaceutical companies,
  technology companies, government agencies, and
  cancer centers

caBIG
CDISC
NCI
PhRMA
BRIDG Advisory Board
caBIG
HL7
CDISC
BRIDG Technical Harmonization Group
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BRIDG projects and contributors
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Principles for model organization

• Make the work process explicit
• Recognizes that concepts and models are in
  different stages of development and harmonization
• Provide a mechanism to scale the development work
• Parallelize the development
• Prevent collaborators from colliding with each
  other
• Allows us to modeling in the open

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Model organization

• Dynamic View
• Captures the business process decomposition of
  the lifecycle of clinical trials research

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Behavioral Aspects of BRIDG
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Behavioral Aspects of BRIDG
Roles are defined in the swim lanes with examples
drawn from discussions with the domain experts
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Behavioral Aspects of BRIDG
The activities are described in activity diagrams
that can be drilled down to provide additional
detail. These are linked to the static (logical)
portions of the model
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Model organization

• Logical View
• Contains three core packages
• Harmonized elements
• Staging Area
• Manual review area
• Addition resources
• HL7 V3 RIM
• Contains the semantics for the static objects
  (data) that is used in clinical trials research
• Currently have 9 subdomain models in the process
  of harmonization

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Current Classes in Core Elements
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Harmonized BRIDG elements
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BRIDG Sub-Projects

• Trial Design Model
• Based on CDISC and FDA/Janus standard
• Developing common concepts and understanding for
  arms, treatment groups, visits, cycles, courses,
  etc.
• At present, input from Pharmaceutical companies
  thru CDISC and FDA
• Current Status
• Recently worked with CDISC SDTM team to model
  SDTM requirements
• Plans to harmonize with BRIDG

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Example Dissimilar Arms
Follow-up
Treatment
Run-In
Screen
Trt Phase 1
Trt Phase 2
Follow-up
Screen
Run-In
Standard Care
Follow-up
Source Diane Wold - GSK
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BRIDG Sub-Projects (contd)

• Clinical Trial Registry
• Objective To define requirements for
  registering a clinical trial in a clinical trial
  repository
• Working with NCI, CDISC, PDQ, clinicaltrials.gov
  and European EUDRACT
• Have recently established collaboration with the
  WHO activity of clinical trials registry
• Becky Kush (CDISC president) on the advisory
  board
• Working with cancerGRID to incorporate and make
  explicit the CONSORT model
• Current Status
• Group has defined a list of 70 elements
• Modeled in BRIDG April 2006
• Planning on developing a HL7 v3 message
• POC Lakshmi Grama, NCI

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CT Registration message
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(No Transcript)
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BRIDG Sub-Projects (contd)

• eDCI message (electronic Data Capture Instrument)
  
• A DCI is a set of related questions for which
  values are to be collected during a clinical
  trial visit.
• This model will be used as an HL7 message
  definition (or a set of definitions) that can be
  used to transmit a DCI Definition between
  databases managed by clinical data management
  systems (CDMS).
• Participation from NCI, CDISC, Oracle
• UML model on bridgproject site --
  https//www.bridgproject.org/edci/
• Current Status
• Requirements have been defined for 1st iteration
• UML class diagram is completed
• Working on building the message specification
  (RMIM)
• POC Don Kacher, Oracle

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DCI Definition (aka CRF)
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SDTM

• SDTM model
• Being harmonized with adverse event reporting,
  CTOM (NCI clinical trial object model) and HL7

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SDTM Class Diagram
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Subprojects

• caAERS
• Project lead Joyce Niland
• Developing an HL7 message and application(s) to
  support adverse event reporting
• Other AE models
• CDC incidence reporting
• HL7 patient safety and public health reporting
• caBIG (caAERS)
• FDA and SDTM (CDISC)
• Harmonization meeting in May with all
  stakeholders to identify commonalities and
  differences between these models, and harmonize
  them into BRIDG

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caAERS
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Harmonization
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Project plan

• Registration of the project
• Allows the BRIDG team to provide information and
  updates
• Regular releases
• Monthly modeling session
• Priorities and resources determined by the BRIDG
  advisory board (and stakeholders)

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Models in the staging area
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What does it mean to adopt BRIDG or harmonize
with BRIDG?

• Adopting and harmonizing with BRIDG is a two-way
  street
• The model is not complete, and harmonization and
  adoption requires participation and contribution
  to BRIDG from others
• The model is new and is changing, so
  harmonization and adoption requires flexibility
  and change
• Early adopters will have a more significant
  impact on the direction and development of BRIDG
• Adopting and harmonization with BRIDG is less
  about a commitment to a specific model, but the
  realization that
• A common standard is a shared good that all can
  benefit from
• It will require contribution and collaboration as
  we collectively determine the best approaches
• It will require compromise and collective action

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BRIDG - Implementation Independent Domain
Analysis Model
Implementation Specific Models
caAERS

• Lab SIG Model
• Study Calendar SIG Model
• Financial SIG Model

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BRIDG - Implementation Independent Domain
Analysis Model
Implementation Specific Models
caAERS

• Lab SIG Model
• Study Calendar SIG Model
• Financial SIG Model

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BRIDG - Implementation Independent Domain
Analysis Model
Implementation Specific Models
caAERS

• Lab SIG Model
• Study Calendar SIG Model
• Financial SIG Model

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Harmonized BRIDG elements
Observation Classes from CTOM and SDTM
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CTOM and SDTM harmonization (work in progress)
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Harmonizing attributes
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Adding tags to provide semantic traceability (and
notes)
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Simple semantic can be tracked in tagged values
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This linking can be extended down to the CDE
level
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More complex relationships
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Achieving interoperability
IMPLEMENTATION SOLUTIONS
STAKEHOLDERS
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BRIDG development
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Cumulative Registered Users
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What have we accomplished?

• BRIDG
• Established excellent collaboration with CDISC,
  HL7 and other caBIG modelers
• Constructed the initial pieces of a comprehensive
  model still much to do
• Have established this model as the HL7 Domain
  analysis model
• Have developed processes and organization of the
  model that will support more scaleable
  collaborative development
• This model will serve as the semantic foundation
  for all data interchange specifications in HL7,
  CDISC, the NCI, and caBIG

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Final thoughts our approach to modeling

• Scope keep it clear and focused (ie, solve a
  problem that exists) and standardize to the
  extend needed
• Refine through experience, and not endless
  discussions. This keeps the modeling effort clear
  and focused
• BRIDG is not complete but the scaffolding is
  there to help organize the analysis and model
  development in subprojects
• Keep it generic, faithful, free of implementation
  specific formalisms, and supporting the
  requirements
• If the tools and models dont work with reality
  it is probably the tools and the models that need
  to change
• If its broke, fix it
• The model is in evolution with known problems
  the problems should be an opportunities for
  improvement and a call to arms, not barriers to
  use
• Model in the open
• Collaborate until it hurts

With thanks to Dipak Kalra for discussion
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BRIDG

• Supports semantic interoperability
• Defines the semantic of static and dynamic
  structures in context
• Provides a mechanism and focus for collaborating
  around shared semantics

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• BRIDG Best Practices draft!
• Developing New Models
• Harmonizing existing Models

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Project Team Activities
Items for submission POC, Project Name, project
description, high-level project schedule,
project Sponsor, etc.
Register Project with BRIDG submit Project info.
BRIDG THC assigns Mentor
A BRIDG mentor will be assigned to your project
Download BRIDG Replica
Begin modeling using BRIDG replica and follow
BRIDG guidelines
Refer to best practices for modeling in BRIDG
environment
Submit BRIDG Harmonization Package to THC
Harmonization Package artifacts the EAP file,
package level xmi Export, Modeling analysis
harmonization document)
Submit BRIDG Harmonization Package to THC
Meet with BRIDG THC to harmonize project model
(virtual or F2F meeting)
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BRIDG THC Activities
Review the Project Registration material.
Assign Mentor to project
BRIDG mentor will be available to answer questions
Take project to BAB and assign priority and
timeline for harmonization
Inform Project POC
May require some negotiations based on other
efforts
Review harmonization Package submission
Perform analysis and prepare for harmonization
meeting
Schedule project Harmonization meeting
Develop harmonization Results package for project
team
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Ways to interact with BRIDG
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De-novo modeling (starting with BRIDG)

• Register the project
• Provide POC and some minimal project info
• BRIDG mentor is assigned to you and your project
  is scheduled for review with the BAB for
  assignment of priority schedule
• Download the BRIDG replica
• Create a new project package in Staging area (for
  both dynamic and static)

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De-novo modeling (starting with BRIDG) (II)

• Begin Modeling
• Model in small groups, vet in large groups
• Identify classes that can be re-used
• Construction of a strawman (possibly using some
  existing BRIDG classes)
• Annotate existing classes with notes on the
  diagram (do not alter core classes or other
  classes in Staging area)
• Develop a modeling analysis and harmonization
  document that identifies updates, additions,
  deletions, change in definitions, comments, etc.
• Periodic review with BRIDG mentor
• Submit the complete pacakge to BRIDG THC/BAB
• xmi export file, EAP file, analysis and
  harmonization document
• Schedule a harmonization meeting between project
  memebers and THC (centra sessions or F2F meeting)

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Existing models

• Register the project
• Provide POC and some minimal project info
• BRIDG mentor is assigned to you and your project
  is scheduled for review with the BAB for
  assignment of priority schedule
• Download the BRIDG replica
• Create a new project package in Staging area (for
  both dynamic and static) and import model
• Identify points of intersection
• Link model elements from other packages in the
  harmonized elements (realize that these elements
  will not be exported when the model is exported)
• Annotate with notes (do not alter core classes or
  other classes in Staging area)

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Existing Models (II)

• Develop analysis and harmonization document that
  identifies updates, additions, deletions, change
  in definitions, comments, etc.
• Periodic review with BRIDG mentor
• Submit the complete package to BRIDG THC/BAB
• xmi export file, EAP file, analysis and
  harmonization document
• Schedule a harmonization meeting between project
  memebers and THC (centra sessions or F2F meeting)

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• Best Practices for Class Modeling
• Annotate Annotate Annotate
• Definitions
• Associations and names

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• BRIDG Harmonization

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• BRIDG Access
• Collaborative Space (GForge)
• Model Management

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Collaborative tools

• GForge site
• www.BRIDGproject.org was the first GForge
  implementation within the CTMS workspace
• Recently, NCI has developed a comprehensive
  GForge site to support caBIG
• Risk is that subproject domain modeling will
  occur in isolation, and not have the level of
  integration into the BRIDG model
• Possible to harmonize these models, but will take
  more time and resources
• Goal
• A single place for all analysis modeling related
  to BRIDG
• Shared forums,
• Shared documents
• Shared learning
• Shared models

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Goal A single place for domain modeling

• Collaborative analysis modeling, with the range
  of stakeholders in the BRIDG project, required
  extensions of the GForge functionality
• Completed a requirements and gap analysis
• Working with the other BRIDG stakeholders to
  develop processes to support not only caBIG but
  others
• Once these issues have been resolved, anticipate
  moving to a shared site for modeling

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Model Management

• Tools
• CVS repository
• Organizes file-level coordination and versioning
  control
• Implemented in the BRIDG GForge site
• Enterprise Architect
• Useful model-level (class/attribute) coordination
  and versioning
• Equivalent to dif and merge of text based files,
  but applies to the model
• Two parts of the same issue
• Different than model vetting or voting

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Replication

• Replication allows different users to work
  independently of one another, and to merge their
  changes at a later time.
• This is inherently a hazardous exercise, and so
  there is no substitution for good collaboration
  and communication

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Enterprise Architect Merge Rules

• Additions are cumulative - i.e. Two replicas
  creating 3 new classes each will result in 6 new
  classes after merging.
• Deletions prevail over modifications, if one
  replica changes a class name and other deletes
  the class, performing a  merge will result in
  both files losing the class.
• EA can generate an interactive dialogue that
  allows a user to review conflicts in the
  replication process.
• EA also allows the construction of a baseline
  that can be used to compare changes within a
  particular file This is useful to know what has
  changed as a group has made changes to a
  particular file.

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Using Replication

• Convert the base project to a Design Master using
  the Make Design Master option in the Tools
  Manage .EAP File submenu).
• Create replicas from the design master using the
  Create New Replica option in the Tools Manage
  .EAP File submenu.                
• Take the replica away and work on it as required,
  then bring it back for synchronization with the
  design master.  
• Synchronize the replicas. During synchronization,
  all changes to both the master and the replica
  are propagated in both directions, so at the end
  they both contain the same information.

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Avoid Change Collisions

• If two or more people make changes to the same
  element, eg. a class, Enterprise Architect will
  arbitrarily overwrite one person's change with
  other other's. To avoid this, different users
  should work on different packages whenever
  possible
• However, since Enterprise Architect does not
  enforce this rule, it is possible for users' work
  to conflict. To minimize the difficulties this
  causes, please note the following guidelines
• If users are likely to have worked in the same
  area of the model - they should both witness the
  synchronization and confirm that they are happy
  with the net result. 
• If small pieces of information have been lost,
  they should be typed into one of the merged
  models after synchronization. 
• If a large piece of information has been lost -
  for example, a large class note that was
  overwritten by another user who had made a minor
  change to the same class  use the Resolve
  Replication Conflicts dialog.

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BRIDG model replica

• BRIDG has a model master and a replica the
  replica is where all of the modeling is currently
  taking place
• Using BRIDG as a starting point allows users to
  take advantage of the EA infrastructure to
  support collaborative model development

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Further Information

• www.CDISC.org
• ncicb.nci.nih.gov
• caBIG.nci.nih.gov
• www.BRIDGproject.org
• fridsma_at_cbmi.pitt.edu
• jevans_at_cdisc.org