BRIDG Update and Tutorial January 30, 2006

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BRIDG Update and TutorialJanuary 30, 2006

• Douglas B. Fridsma, MD, PhD
• University of Pittsburgh
• with
• Charlie Mead,
• Smita Hastak,
• Julie Evans
• and a cast of thousands

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Acknowledgements leadership

• Leadership and collaboration
• CDISC board members
• Becky Kush, CDISC
• Sue Dubman, NCI
• Charlie Mead, HL7
• Barbara Tardiff, Linda Quade, Randy Levine, RCRIM
  technical committee of HL7

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Acknowledgements modelers

• Christo Andonyadis
• Greg Anglin
• Lisa Chatterjee
• Julie Evans
• Douglas B Fridsma
• Smita Hastak
• Joyce Niland
• John Speakman
• Cara Willoughby
• Diane Wold
• Peter Ambramovich

• Ed Helton
• Pierre-Yves Lastic
• Tony Friebel
• Don Kacher
• Barbara Tardiff
• Chuck Jaffe
• Frank Newby
• Sally Cassels
• Nitin Gupta
• Landen Bain
• Laura Altshuler
• Steve Ruberg
• Elaine Job
• Becky Kush
• Sylvia Collins
• Udo Siegman
• David Hardison
• David Iberson-Hurst

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AcknowledgementsOrganizations

• Pharmaceutical companies
• AstraZeneca
• Boehringer-Ingelheim
• Eli Lilly
• GlaxoSmithKline
• Merck
• Novartis
• Pfizer
• Sanofi-Aventis

• Technology companies
• ScenPro
• IBM
• SAS
• Fast track
• SAIC
• BAH
• Oracle

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Current Organization of the BRIDG project
NCI
caBIG
PhRMA
CDISC

• 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

BRIDG Advisory Board
caBIG
HL7
CDISC
BRIDG Technical Harmonization Group
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How do you find partners to help establish
standards?
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BRIDG projects and contributors
BRIDG model
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What is BRIDG?

• 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
• A bridge between
• clinical trial domain experts and technical
  experts
• different models of clinical trials information
• A formal model of the shared semantics of
  regulated clinical trials research
• A tool for coordination and collaboration
• The semantic foundation for application and
  message development in HL7, caBIG, and CDISC

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The Map is not the Territory(Bertrand Russell)

• Domain Experts have a mental map of the
  Problem Space
• Noam Chomsky Syntactic Structures (1975)
• Deletion (filtered/missing details)
• Distortion (incorrect or modified details)
• Generalization (abstractions via rules, beliefs,
  principles)
• Distortion and Generalization share
• Inappropriate/incorrect use of universal
  qualifiers
• All
• Everyone
• Always
• Never
• Nobody
• None

Acknowledgment Charlie Mead
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The Map is not the Territory

• Deletion They use the system to find
  information about clinical trials.
• Challenge Who uses the system?
• Response Clinical research coordinators,
  patients, and investigators.
• Distortion You cant enter a clinical trial
  protocol until you have an protocol
  identification number.
• Challenge Are there any circumstances where
  you can enter a protocol without an
  identification number?
• Response Yes, two circumstances.
• Generalization Everyone must have a log-on ID
  to access the information in the system.
• Challenge Are there any system users that can
  access the information without an log-on ID?
• Response Organizations and cooperative groups
  may use the API to access the information
  directly.

Acknowledgment Charlie Mead
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What Is A Domain Analysis Model?

• An implementation-independent view of the
  Problem Space from the Domain Experts
  perspective
• Minimum components
• Static View
• Concepts, Attributes, Relationships
• Complete, unambiguous documentation (GLOSSARY)
• UML Class Diagram
• Appropriate partitioning of sub-domains and
  layers 0f abstraction (Packages)
• Exemplar Instance Diagrams
• Dynamic View
• Storyboards
• UML Activity Diagram representations of
  Storyboards
• State diagrams of suitably interesting static
  classes
• For software development, the domain analysis
  model is similar to a formal requirements
  specification of the problem space.

Acknowledgment Charlie Mead
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Community review

• Since last Face to Face meeting, model has been
  reviewed by a number of caBIG and HL7 members
• Significant increase in participation in the
  BRIDG GForge site

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Cumulative Registered Users
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Feedback from the initial BRIDG model

• The model is big, complex, and difficult to
  navigate
• The scope of the model is ill-defined
• The levels of abstraction are inconsistent
• The model is static heavy, and needs additional
  work on the dynamic aspects of the model, linked
  to the static structures

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Improvements

• Educational programs
• Need to provide more information about BRIDG at
  all levels
• Additional work on the dynamic aspects of the
  model
• Business process decomposition
• Changed the structure of the model to anticipate
  multiple developers working toward a common model
• Prior Art, Staging area, Core model
• Entities, Roles, Participations, Acts
• Beginning to develop a best practice for how to
  model using the BRIDG model
• CVS branches based on open-source approaches to
  collaboration
• Replication and synchronization using EA

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Establishing a comprehensive educational program
around BRIDG

• Targeting various learners
• Domain experts
• How do you contribute your expertise into the
  model?
• Storyboards, use cases
• Modeling experts
• How do you take the storyboards and use cases and
  construct formal models of the expertise?
• Modeling best practice
• Technical experts
• How do you take these formal models of expertise
  and create applications that address these
  problems?
• Various ways to learn
• HL7 tutorial in January 2006
• Webinar in February and March 2006
• CDISC/HL7 joint meeting in Berlin, April 2006
• Bootcamp for deep understanding of the model
  (?March)

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Restructuring BRIDG

• Moved much of the old parts of the model that
  reflect the evolution of our thinking to a
  separate package
• Created a structure in the model that is similar
  to the RIM backbone to help organize the model
• Recognized that Entities and Roles will be
  relatively stable, but the real complexity will
  be in the activities and (possibly) the
  participations
• Created views that reflect smaller parts of the
  model
• Staging area in the model for parts of the model
  that are in the process of harmonization

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Current projects in BRIDG

• Models being staged for harmonization
• Clinical Trials Object Model (CTOM) from NCI
  (80)
• SDTM from CDISC (20)
• caAERS from City of Hope AND Patient Safety model
  from HL7 (pending, mid-Feb)
• eDCI model from NCI/Oracle (pending)

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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
• Requirements being developed by NCI and CDISC
• Working with 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
• Jan 25-28 harmonization session in Washington
  DC with CDISC/HL7/WHO models
• Working with cancerGRID to incorporate and make
  explicit the CONSORT model
• Current Status
• Group has defined a list of 70 elements
• Planning to model these into BRIDG
• Planning on developing a HL7 v3 message
• POC Lakshmi Grama, NCI

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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
• Plans to harmonize with BRIDG
• Working on building the message specification
  (RMIM)
• POC Don Kacher, Oracle

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eDCI UML class Diagram
DCI Definition (aka CRF)
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BRIDG Sub-Projects (contd)

• Protocol Representation
• Integral part of the BRIDG model
• Initial requirements based on CDISC developed
  list of elements
• This list of elements were vetted by CDISC
  constituents and represent their international
  community
• It is based on ICH E6 and has a Document view of
  the Protocol
• Current Status
• Work in progress integrating back into the new
  BRIDG organization

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BRIDG development
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Models to be harmonized
Model Name Stakeholder Completed? Imported? Harmonized?
CTOM NCI Yes Yes 80
caAERS NCI Yes No Annotated, not harmonized
SDTM CDISC Yes Yes 20
AE (other) CDISC (SDTM) FDA, CDC, HL7 (ICSR) Yes Harmonize with caAERS
CT Registry CDISC Under development Modeling in BRIDG
CONSORT UK CancerGRID, WHO Yes Yes Harmonize with CT Registry
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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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Lessons learned (so far) in domain 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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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
• Create replicas from the design master using the
  Create New Replica option              
• 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

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Avoid Change Collisions

• 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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CVS repository

• Modeled after open source approaches
• Trunk
• the releases of the model are here (V 1.0, V
  2.0, etc)
• Harmonization branch
• Similar to a bug fix branch to help with the
  model construction (V1.1, V 1.2)
• Development branches
• Sub-project development and new model development
• Will be harmonized into the harmonization branch,
  and then lead to a release to support a software
  project

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How do I create an application based on BRIDG?
NCI
Version 1
BRIDG trunk

• We have checked in the original version of the
  BRIDG model to the CVS trunk, and created a
  released that version of the model.
• The trunk represents the released version of
  the model, and may be tied to requirements
  traceability.

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How do I create an application based on BRIDG?
NCI
Version 1
BRIDG trunk

• The Harmonization branch is similar to a bug
  fix it allows developers to break the model,
  fix things that need to be changed, and maintain
  versioning control while they do it.

Version 1
V 1.1
Harmonization branch
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CVS repository

• Access control
• Desiderata Protect the trunk of the CVS
  repository from inadvertent check-in, while
  allowing free access to the CVS repository to the
  various subprojects leads.
• CVS
• Access to check-in on the CVS repository requires
  root level access for everyone
• Risk is that the CVS repository is corrupted
• Subversion
• Better mechanism for access control allows the
  protection of the CVS trunk while allowing free
  access to the branches in the tree.
• Examining the benefits and costs of migration

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How do I create an application based on BRIDG?
NCI
Version 1
BRIDG trunk

• When a team begins a new project to develop a
  message or application, they would check out the
  most recent version of the model that is
  currently developed. Typically this is the
  Harmonization branch.

Version 1
V 1.1
Harmonization branch
eDCI development branch
eDCI 1.1
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How do I create a message based on BRIDG?
Version 1
BRIDG trunk

• New projects will begin in the same way
  checking out the current version of the model
  from the harmonization branch
• We now have three versions of the model, all
  working in parallel.
• Although EA helps with synchronizing models,
  there is no substitute for good coordination and
  collaboration.

Version 1
V 1.1
V 1.2
Harmonization branch
CAERs development branch
caERs 1.1
eDCI development branch
eDCI 1.1
eDCI 1.2
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How do I create an application based on BRIDG?
NCI

• Development can continue on both of these
  branches, using the master-replica features of
  Enterprise Architect

Version 1
BRIDG trunk
Version 1
V 1.1
V 1.2
Harmonization branch
CAERs development branch
eDCI development branch
eDCI 1.1
eDCI 1.2
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How do I create an application based on BRIDG?
NCI

• New projects will repeat the process of checkout,
  modeling, etc.
• As the development continues, there will be
  periodic new releases of the model.
• The arrow from version 1 to version two
  represents some vetting of the model from
  stakeholders in the project and incorporation of
  harmonization branch changes.

Version 1
Version 2
BRIDG trunk
Version 1
V 1.1
V 1.2
V 1.3
Harmonization branch
CAERs development branch
caERs 1.1
caERs 1.2
eDCI development branch
eDCI 1.1
eDCI 1.2
eDCI 1.3
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How do I create an application based on BRIDG?
NCI
Version 2
Version 3
BRIDG trunk

• As a development branch matures, it can be merged
  with the harmonization branch (using
  master-replicas)
• The model then can be vetted with the
  stakeholders, and a release generated

V 1.3
V 1.3
V 1.3
Harmonization branch
CAERs development branch
caERs 1.2
caERs 1.3
caERs 1.4
eDCI development branch
eDCI 1.3
eDCI 1.2
eDCI 1.3
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HL7 Vetting Process (From RCRIM)
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How do I create an application based on BRIDG?
NCI
Version 3
BRIDG trunk
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How do I create an application based on BRIDG?
NCI
Version 3
BRIDG trunk

• A portion of the BRIDG model will need to be
  annotated and modified according to the HL7 HDF
  implementation specifications
• HL7 is an implementation, and so additional
  annotation and modification may be necessary to
  the model
• Realize that the HDF processes are currently
  underway, and will inform this process

Annotated model
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How do I create an application based on BRIDG?
NCI
Version 3
BRIDG trunk

• The output of the processes related to the
  semantic connector and UML loader will be used
  for application development

Annotated model
Semantic Connector
UML Loader
caCORE tools
Application
Application Module
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Other issues

• GREATLY simplified, but a lot of people are
  working on the processes
• NCICB with the processes around the UML loader
  and semantic connector
• HL7 with regard to using the model for message
  development
• BRIDG group working on processes that touch on
  BRIDG
• Input/outputs
• Versioning
• Harmonization
• Collaboration and coordination

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Technology and Processes

• Technology and process go hand-in-hand
• Features in EA for synchronization
• Features of CVS repository and gForge
• Vertical vs Horizontal project integration
• CVS vs subversion and branch-level access
  controls
• Tools can make collaboration easy or hard
• Shared tooling will allow collaboration to
  progress more quickly
• Sharing semantics requires multiple different
  tool listservs, discussion forums, conference
  calls, document exchanges, etc.
• Common places for collaboration are key to
  rapidly converging on consensus

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Whats necessary to make the BRIDG model happen?

• Competing prioritiescollaboration vs deadlines
• Not mutually exclusive, but requires
• Adequate resources to support collaboration and
  harmonization tasks
• A plan for circling back for elements and
  models not completely harmonized
• Benefit
• Rapid development and processes driven by real
  needs in the community

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BRIDG model
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Organization of BRIDG

• Dynamic aspects of domain
• Business process decomposition
• Driven by story boards and discussion
• Model principles
• Swimlanes become roles in the static model
• Objects link to static representations in model
• 8-12 activities per page is a goal
• Iterative process between storyboard and activity
  diagram

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Organization of BRIDG

• Areas in the model
• Supporting packages
• Background
• Resources
• Instance diagrams
• Staging Packages
• This is where models go that are waiting to be
  harmonized
• Core packages
• Shared classes
• Entities and Roles
• Activities and Participations

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SPR SIG Discussion

• Tasks that we need to do within the SPR SIG
• Review and vet components in BRIDG
• Prioritize, based on needs within the caBIG
  community
• Add missing definitions and semantics to model
  elements
• Support other SIG efforts to develop subproject
  models
• Other groups (ie CDISC) doing similar tasks?
• Review model best practices
• Do we have the expertise within our group to do
  these tasks?
• What resources do we need to move forward with
  the work?

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SPR SIG Discussion (II)

• Can we identify clear deliverables and review
  cycles to support the modeling effort?
• Are there specific topics not covered by other
  SIGs that we wish to add to the BRIDG model?
• Eligibility Criteria?
• Trial Design elements?
• Statistical Analysis?
• Protocol Authoring?
• Internal/external review and trial management?
• IRB, tracking, etc
• Where do we fit in the Clinical trials life-cycle
  management?

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Goals

• Development of a community derived priority list
• Develop plan for deliverables within that list
• link those to necessary resources and assign to
  individuals within the group