Slide 1 - caBIG

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					         BRIDG: A Shared Analysis
         Model of the Domain of
         Clinical Trials Research


      Douglas B. Fridsma, MD, PhD
    Center for Biomedical Informatics
University of Pittsburgh School of Medicine
What is BRIDG?


• An open community of stakeholders interested in
  developing standards for exchanging information
  about clinical trials
• 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
• The semantic foundation for application and message
  development in HL7, caBIG, and CDISC
  A Team Effort

Leadership and collaboration   Modeling Team
                               •   Christo Andonyadis
• Sue Dubman, NCI              •   Peter Abramovitsch
• Becky Kush, CDISC            •   Greg Anglin
• Linda Quade, Randy Levin,    •   Lisa Chatterjee
   Barbara Tardiff, HL7        •   Julie Evans
                               •   Douglas B Fridsma
• Charlie Mead, HL7            •   Smita Hastak
                               •   Ray Heimbuch
                               •   Charlie Mead
                               •   Joyce Niland
                               •   John Speakman
                               •   Cara Willoughby
                               •   Diane Wold

                               •   The Trial Design group in CDISC
Team Members (2)

•   Julie Evans           Current modeling team
•   Ed Helton                –   Christo Andonyadis
•   Pierre-Yves Lastic       –   Greg Anglin
•   Tony Friebel             –   Lisa Chatterjee
•   Don Kacher               –   Julie Evans
•   Barbara Tardiff          –   Douglas B Fridsma
•   Chuck Jaffe              –   Smita Hastak
•   Frank Newby              –   Joel Hoffman
•   Sally Cassels            –   Charlie Mead
•   Nitin Gupta              –   Joyce Niland
•   Landen Bain              –   John Speakman
•   Laura Altshuler          –   Cara Willoughby
•   Steve Ruberg,            –   Diane Wold
•   Elaine Job
•   Becky Kush
•   Sylvia Collins
•   Udo Siegman
•   David Hardison
•   David Iberson-Hurst
  BRIDG Development Philosophy

• 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
• Keep it generic, faithful, free of implementation specific formalisms,
  and supporting the requirements
• Model in the open
• Collaborate until it hurts
• If the tools and models don‟t work with reality – it is probably the
  tools and the models that need to change




                   With thanks to Dipak Kalra for discussion
The current stakeholders in BRIDG

 • Health Level Seven (HL7)
    – BRIDG is the domain analysis model (DAM) for HL7 RCRIM TC

 • Clinical Data Interchange Standards Consortium (CDISC)
    – Consortium of pharmaceutical companies
    – Develops standards for regulatory reporting and drug development
      submissions
    – Key participant in HL7

 • caBIG CTMS workspace and NCI
    – Has real needs for applications and interoperability standards
    – Funding the participation of cancer centers
    – Has created a focus for integrating various standards organizations
BRIDG organization


• BRIDG advisory board
   – Strategic direction with representation from all the
     stakeholders (CDISC, HL7, caBIG)
• Technical Harmonization group
   – Managing the technical process of harmonizing and
     mentoring subprojects
       • Small group of individuals charged with the technical aspects of
         harmonization
       • Have to make choices, but approval and vetting rests with
         stakeholders
cd Comprehensiv e Logical Model




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                Design Concepts::Masking

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       level:                                   Protocol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       objectOfMasking (set):                  Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       procedureToBreak:                         Control
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       unmaskTriggerEvent (set):


                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  HasSubElements
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  «Period»
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Design Concepts::Element

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    -    Children: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Protocol Concepts::DesignCharacteristic                          Protocol                                                                                                                                                                                                -    epochType: EpochTypes

   Name:                   Comprehensive Logical Model                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +     synopsis:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Configuration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Protocol                     +     type: test value domain = a,d,f,g
   Author:                 Fridsma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Concepts::                    +     summaryDescription:                                                                                                                                                                                                                   AbstractActivity                                                  hasScheduledEvents                                                              hasElements
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Scope                       +     summaryCode:                                                                                                                                                                                           Design Concepts::PlannedTask
   Version:                1.0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +     detailedMethodDescription:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     displayName: char[]
   Created:                7/22/2005 2:53:51 PM                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        +     detailedMethodCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Protocol                                                                                                                           -     whoPerforms: int
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     sequence: int
   Updated:                7/29/2005 2:33:32 PM                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Concepts::Bias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     procDefID: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     sourceText: char[]                                                                                                                SubjectEvent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Design Concepts::Arm
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      Protocol Concepts::StudyBackground(w hy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Design Concepts::ProtocolEv ent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    nameOfArm: char[]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    description: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -   parent: AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    hasElements                                                                                          -    plannedEnrollmentPerArm: char[]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    summaryOfPreviousFindings: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -   eventType: ScheduledEventType                                                  -    randomizationWeightForArn: int
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    summaryOfRisksAndBenefits: PSMDescription                           Protocol Concepts::StudyObligation                                                                                                                                                                                                                                                                                                                                                                                                              -   studyOffset: PSMInterval
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               1                                                                                                                                                                         -    associatedSchedules: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    justificationOfObjectives: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -   studyDayOrTime: char
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    justificationOfApproach: PSMDescription                            +   type: ENUMERATED
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    populationDescription: PSMDescription                              +   description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForEndpoints: PSMDescription                              +   commissioningParty:                                                                                                    Design Concepts::                                Protocol Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForDesign: PSMDescription                                 +   responsibleParty:                                                                                                       Randomization                                                                                                                                                                                                        taskAtEvent                               tasksPerformedThisSchedule
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Concurrency
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForMasking: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       minimumBlockSize:                                                                                                                                                                                                                                                                                            hasOngoingEvents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForControl: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForAnalysisApproach: PSMDescription                                                                                                                                              +       maximumBlockSize:


                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               1..*

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          +correlativeStudy 0..*                                                                                                                                                                                                                                                                            Design Concepts::Ev entTask                                                                                                                                                hasArms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Design Concepts::StudySchedule
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               BusinessObj ects::Study
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -   localFacilityType: LocalFacilityType                                                       -       Periods: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   startDate: Date                                +primaryStudy 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -   centralFacilitityType: CentralFacilitiyType                                                -       Tasks: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   endDate: Date                                                                                                                                                                                                                                                                                                                       -   eventID: OID                                                                                                                                       hasUnscheduledEvents
                                                                                                                                                                                                                                                                                                                                                                                                                                            BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -       TaskVisits: Set                                                                                                      SubjectEvent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 BusinessObj ects:                       +   type: PSMCodedConcept                                                                                                                                                                                                                                                                                                               -   taskID: OID
                                                                                                                                                                                                                                                                                                                                                                                                                                        ClinicalDev elopmentPlan                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                -       associatedArms: Set                                                               Design Concepts::UnscheduledEv ent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   :Amendment                            +   phase: PSMCodedConcept                                                                                                                                                                                                                                                                                                              -   purposes: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   randomizedIndicator: Text                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             -      eventType: UnscheduledEventType
                                                                                                                                                                                                                                                                                                                                                                                              -_DevelopmentPlan      *
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   SubjectType: PSMCodedConcept                                                                                                                                 BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Activ itySchedule (the "how ",
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      "w here", "w hen", "w ho")
                                                                                                                                                                                                                                                                                                                                                                                                           BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Protocol Concepts::StudyObj ectiv e(w hat)                                            +    description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                      IntegratedDev elopmentPlan
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     1                                                           +   description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +   intentCode: SET ENUMERATED
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +   objectiveType: ENUM{Primary,Secondary,Ancillary}                                                                                                                                                                                                       hasPurposes
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +   id: PSMID
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   «execution mode»                                                                                                                                                           Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                           *                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   StudyActiv ityRef
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Scheduled Sub Activities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   -      activityID: OID
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              0..*

                                                                                                                                                                                                                                                                                                                                                                                                                                                Protocol Concepts::StudyDocument                                                                                                                                  -source              1     1..*
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  objective                                  Protocol Concepts::Outcome
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   effectiveEndDate: DATETIME                                            BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Defined By
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1..* -    description: BRIDGDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   version:                                                              ProtocolDocument                                                                                                                                                                                                                                             Design Concepts::Ev entTaskPurpose                                                                    BasicTypes::StudyDatum
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    ranking: OutcomeRank
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   author: SET                                                                                                                                                                                                                                                                       as Measured By
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    associatedObjective: Set                                                                                 -   isBaseline: boolean                                                                                -    complete: bool
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   effectiveStartDate: DATETIME                                                                                                                                                                                                                                                                                                                                                                                                          -    value: Value
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    analyticMethods: Set                                                                                     -   purposeType: PurposeType                                                                                                                                                             Defined By
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   ID: SET PSMID                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    asMeasuredBy: Set                                                                                        -   associatedOutcome:                                                                                 -    timestamp: timestamp                   isKindOf                                                                                                                                                    «ODM:ItemDef»
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   documentID:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    outcomeVariable:                                                                                                                                                                                                -    itemOID:                                                                                                                                                                   kindOf                 Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   type: ENUMERATED = formal plus non...                               BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             «abstract»
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    threshold:                                                                                                                                                                                                                                                                                                                                                    Design                                                  PlannedInterv ention
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   description: PSMDescription                                         ClinicalStudyReport
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   title:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   status: PSMStatus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               StudyActivityDef
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   confidentialityCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BasicTypes::AnalysisVariableInst
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   businessProcessMode: PSMBusinessProcessMode                                                                                                                                                                                                                                                                                                                                                   associatedVariable
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            «ODM ItemData»                                             «ODM:ItemData»                         -    roleInAnalysis: RoleInAnalysisTypes                                                                                    kindOfActivityRelation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      Design Concepts::Observ ation                                    Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                         SubjectDatum
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               -   transactionType:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            CommunicationRecord
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   -   subjectID: int
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BasicTypes::StudyVariable

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -    OID: long
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  «ODM:ItemDef»
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -    Name: char
                                                                                                                                                                                                                                                                                                                                                                                                                                                     BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -    unitOfMeasureID: OID
                                                                                                                                                                                                                                                                                                                                                                                                                                                    SupplementalMaterial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       PlannedObserv ation
                                                                                                                                                                                                                                                                                                                                                                                                                +source 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    minValid:
                                                                                                                                                                                                                                                                                                                                                                                           Entities and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -    maxValid:
                                                                                                                                                                                                                                                                                                                                                                                                                                         +     type:
                                                                                                                                                                                                                                                                                                                                                                                              Roles::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             -    controlledName: ENUM
                                                                                                                                                                                                                                                                                                                                                                                                                  +target 0..*           +     description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                         ResearchProgram                                                                                                                                                                                                                                                                                                                                                                                                                                          «ODM ItemData»                          «ODM:ItemData»
                                                                                                                                                                                                                                                                                                                                                                                                                                         +     version:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Design Concepts::                      Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                         +    type:                                      +     ID: SET PSMID
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               BasicTypes::RIMActiv ityRelationship                                                                                                                                                                                                                                               DiagnosticImage                       TreatmentConfirmed

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     relationshipCode: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     sequenceNumber: NUMBER
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     pauseCriterion:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     checkpointCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     splitCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     joinCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     negationIndicator: BOOLEAN
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     conjunctionCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                 Entities and Roles::
                                                                                                                                                                                                                                                                                                                                                                                                                                         Study                                                                                                                                                                                                                                                 restates Objective
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Statistical Concepts::StatisticalConceptArea                                                                                          Statistical Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       BusinessObj ects::                                                                                                                                                                 StatisticalAnalysisSet
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                -     evaluableSubjectDefinition: char                                           hasAnalysisSets
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           *          *                                                                                                                                                              StatisticalAnalysisPlan
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                -     intentToTreatPopulation: char                                                                                       +     description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                             1..*                                                                                                                                                                                                                                                                                                                               -     clinicallyMeaningfulDifference: char                                                                                -     scopeType: AnalysisScopeTypes
                               Entities and Roles::Place                                        Entities and Roles::Entity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -     proceduresForMissingData: char
                           +       gpsText:                                                                                                                                                                                                                                                                                                                                                                                              1                                                                                                                                                                                                                                                                                                                                      -     statSoftware: char
                                                                                  +   instantiationType: ENUM {Placeholder, Actual}                                                                                                   Entities and Roles::Role                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     BasicTypes::ActActRelation
                           -       mobileInd: boolean                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -     methodForMinimizingBias: char                                                                                                                      hasCriteria
                                                                                  +   id: SET <PSMID>
                           -       addr:                                                                                            1                                                                                   * +                                                                                                                                                                   Entities and Roles::Activ ityRoleRelationship                                                                                                                                                                                                                                                                                                                                     -     subjectReplacementStrategy: char                                                                                                                                                                                                              -   description: BRIDGDescription
                                                                                  +   name: string                                                                                                                            id:
                           -       directionsText:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          hasHypotheses                       -     randAndStratificationProcedures: char                                                                                                                                                                                                         -   relationQualifier: BRIDGCodedConcept
                                                                                  +   code: PSMCodedConcept                                                                                                               +   code: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                          +    relationshipCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    -   mode: PSMBusinessProcessMode
                           -       positionText:                                  +   quantity: int                                                                                                                       +   name:
                                                                                                                                                                                                                                                                                                                                                                                          +    sequenceNumber: NUMBER                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               -   effectiveTime: BRIDGInterval
                                                                                  +   description: PSMDescription                                                                                                         +   status:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Statistical Concepts::AnalysisSetCriterion
                                                                                                                                                                                                                                                                                                                                                                                          +    negationIndicator: BOOLEAN                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           +   priorityNumber: NUMBER
                                                                                  +   statusCode: BRIDGStatus                       1                                                                                     +   effectiveStartDate:
                                                                                                                                                                                                                                                                                                                                                                                          +    time: TimingSpecification                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -           description: char                                                                                 -   negationRule: AbstractRule
                                                                                  +   existenceTime: BRIDGInterval                                                                                                        +   effectiveEndDate:
                                                                                                                                                                                                                                                                                                                                                                                          +    contactMediumCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     -           subgroupVariable: StudyDatum                                                                      -   detail: char
                                                                                  +   riskCode: PSMCodedConcept                                                                                                           +   geographicAddress:                             1                                                                                                          * +    targetRoleAwarenessCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                               -           sequence: int                                                                                     -   sourceAct: AbstractActivity
                    Entities and Roles::Organization                              +   handlingCode: PSMCodedConcept                                                                                                       +   electronicCommAddr:
                                                                                                                                                                                                                                                                                                                                                                                          +    signatureCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       -   destAct: AbstractActivity
                                                                                  +   contactInformation: SET <PSMContactAddr>                                                                                            +   certificate/licenseText:
                                                                                                                                                                                                                                                                                                                                                                                          +    signature: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            -   sequence: int
                   +   geographicAddress:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Statistical Concepts::HypothesisTest
                                                                                                                                                                                                                                                                                                                                                                                          +    slotReservationIndicator: BOOLEAN
                   +   electronicCommAddr:
                                                                                                                                                                                                                                                                                                                                                                                          +    substitionConditionCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +   «property» relationQualifier() : PSMCodedConcept
                   +   standardIndustryClassCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               +   significanceLevel: double
                                                                                                                                                                                                                                                                                                                                                                                          +    id: PSMID                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +   «property» sourceAct() : AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                +   lowerRejectionRegion: int
                                                                                                                                                                                                                                                                                                                                                                                          +    status: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                        hasAnalysisSets
                                                                                                                                                                                                                                                 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +   upperRejectionRegion: int                                                                                                                                                                                                                                                       +   «property» destAct() : AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                           1..*                                                                                                                                                                                                                                                                                 +   testStatistic:                                                       hasAnalyses
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Statistical Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                +   comparisonType: AnalyticComparisonTypes
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       SampleSizeCalculation
                                                                        Entities and Roles::Liv ingEntity                 Entities and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          #   associatedSummaryVariables:
                                                                                                                         Roles::Material                                                                                                                                                                           Entities and Roles::Employee                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           +       clinicalJustification: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -source
                                                                       +   birthTime:
                                                                                                                                                                                                                                                                                                            +      jobCode: PSMCodedConcept                                                                                                                                                                                                      activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +target activity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             kindOfActRelation
                                                                       +   sex:                                          +   formCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -source
                                                                       +   deceasedInd: boolean                                                                                                                                                                                                                                                                                                                                                                            activity                                                                AbstractActivity
                                                                       +   deceasedTime:                                                                                                                                                                                                                                                                                                                                                                                                  1                                                                                                                                                                                                                                                                                                             kindOfAnalysis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BasicTypes::RIMActivity
                                                                       -   multipleBirthInd: boolean                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             kindOfAnalysis
                                                                       -   multipleBirthOrderNumber: int                                                                                                                                                                                                                                                                                                                                                                                      +      businessProcessMode: PSMBusinessProcessMode                                                                                                                                                                                                                                                        -_StatisticalAnalysisSet      *
                                                                       -   organDonorInd: boolean                                                                                                                                                                                                                                                                                                                                                                                             +      code: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                         Statistical Concepts::
                                                                                                                                                                                                                                                                                            Entities and Roles::Patient
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Statistical Concepts::Hypothesis                                                                                                                                                                            StatisticalAssumption                                                                                        BasicTypes::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      derivationExpression: TEXT
                                                                                                                                                                                                                                                                                            +   confidentialityCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            AbstractRule
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      status: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                  AbstractActivity                                                            +     description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    +TerminatingActivity 1..*                                                                                                                                                    +   statement: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      availabilityTime: TimingSpecification                                                                                                                                                                                                                                               -_Hypothesis                                                                                                                                                                                                                                                     -     isExclusive: bool
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -   associatedObjective:                                                                       Statistical Concepts::Analysis
                                                                                                                  Entities and Roles::          OProtocolStructure::                                                                                                                                                                                                                                                                                                                          +      priorityCode: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       *                                                                                         -   clinicallySignificantDiff: char                     *
                                                                                                                 ManufacturedMaterial            ElectronicSystem                                                                                                                                                                                                                                                                                                                             +      confidentialityCode: PSMCodedConcept                                                                                                                                                                                                                                                                     +    description: PSMDescription                                                                                                                                                                                                            +     run() : bool
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      repeatNumber: rangeOfIntegers               +EndEvent 1                                                                                                                                                                                                                                                  +    analysisType: Set{AnalysisTypes}
                                                                                                             -     lotNumberText: string                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Protocol Concepts::StudyObj ectiv eRelationship                                                                                                                                                                                                                                                                     hasAssumptions
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      interruptibleIndicator: BOOLEAN                                                                                                                                                                                                                                                      hasAnalyses         +    analysisRole:
                                                                                                             -     expirationTime:                                                                                                                                                                                                                                                                                                                                                            +      uncertaintyCode: CodedConcept                                                                                                                                                                                                                                                                            +    rationaleForAnalysisApproach: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   +StartEvent 1                                                               +    type: PSMCodedConcept
                                                                                                             -     stabilityTime:                                                                                                                                                                                                                                                                                                                                                             +      reasonCode: PSMCodedConcept                                                                                                                                                                                                                                                                              #    associatedStrategy:
                                                                                                                                                                                                                                                                                  Entities and Roles::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              #    associatedHypotheses:                                                    hasModel                              Statistical Concepts::StatisticalModel
                                                                                                                                                                                                                                                                                         Access
                           Entities and Roles::Person
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    +FirstActivity 1..*
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      +           description: PSMDescription                                                                                implements          Implements           implements
                       +        geographicAddress:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             hasChildAnalyses                                                                                                         #           outputStatistic: StudyVariable
                       -        maritalStatusCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           computations: Set
                       -        educationLevelCode:
                                                                    Entities and Roles::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  hasStrategy                                                                 -           assumptions: Set
                       +        raceCode:
                       -        disabilityCode:                    NonPersonLiv ingEntity
                       -        livingArrangementCdoe:
                                                                   +   strain:
                       +        electronicCommAddr:
                                                                   -   genderStatusCode:                          Entities and Roles::Dev ice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  hasComputations
                       -        religiousAffiliationCode:
                       +        ethnicGroupCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             *                                                                                                                                                                                                                                                     Statistical Concepts::                                                                                                                                                             «implementationClass»            «implementationClass»                       «implementationClass»
                                                                                                         -       manufacturerModelName:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Design Concepts::                BusinessObj ects::                          Design Concepts::
                                                                                                         -       softwareName:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   SequentialAnalysisStrategy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          TemporalRule                     BusinessRule                               ClinicalDecision
                                                                                                         -       localRemoteControlStateCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      alphaSpendingFunction:
                                                                                                         -       alertLevelCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Statistical Concepts::Computation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      timingFunction:
                                                                                                         -       lastCalibrationTime:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      analysis:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      trialAdjustmentRule:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   +IsContainedIn               +sourceActivity 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         1..* +targetActivity                                                                                                                                                                                                                                                                                                                                                                                         -           algorithm: char
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           input: AbstractStatisticalParameter
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           output: AbstractStatisticalParameter




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +contains 1                +generates 0..*
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  +passedTo

                                                                                                                                                                                                                                                                                                                                                                                                                                                                    OProtocolStructure::                             OProtocolStructure::                                                                                                                                                                                                                                                                                                                                                                                                                           hasSchedules
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  ResponsibilityAssignment                           Activ ityDeriv edData
                                                                                                                                                                                                                                                                                                                                                                                                                                                       1




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Plans::Protocol/Plan                                               BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        SiteSubj ectManagementProj ectPlan




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1..*

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          SiteStudyManagementProj ectPlan

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   SponsorStudyManagementProj ectPlan
                                                                                                  BasicTypes::BRIDGInterv al                                         OStudy Design and Data Collection::
                                                                                                                                                                                                                                                                                       BusinessObj ects:
                           BasicTypes::BRIDGBusinessProcessMode                                                                                                        OBRIDGDeriv ationExpression
                                                                                        -   startTime: timestamp                                                                                                                                                                               :
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             1 1..*
                                                                                        +   endTime: timestamp                                             +     type: ENUM{transformation, selection}                                                                                 RegulatoryRecord
                       +       modeValue: ENUM {Plan, Execute}
                                                                                                                                                           +     rule: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              BusinessObj ects::Inv estigatorRecruitmentPlan
                                                                                                                                                           +     id: PSMID
                                                                                                                                                           +     name: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 ClinicalTrialMaterialPlans


                                                                                                                                                                                                                                                                    BusinessObj ects::
                                                                                                                                                                OStudy Design and Data Collection::OBRIDGTransition                                              RandomizationAssignment                  BusinessObj ects::               BusinessObj ects::Guide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         BusinessObj ects::
                                                                                                     BasicTypes::BRIDGID                                                                                                                                                                                  EnrollmentRecord                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            DataMonitoringCommitteePlan
                                                                                                                                                            +    criterion: RULE                                                                                 +    randomizationCode:
                                                                                            +   source: Text                                                +    eventName: TEXT                                                                                 +    subjectID:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 BusinessObj ects::BiospecimenPlan
                                                                                            +   version: Text                                                                                                                                                    +    assignmentDateTime:
                                                                                            +   value: Text



                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     DataManagementPlan
                                                                                                                                                                                    BasicTypes::BRIDGAnalysisVariable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            BusinessObj ects::AssayProcedures
                                                                                                BasicTypes::BRIDGCodedConcept
                                                                                                                                                           +     name: TEXT
                                                                                            -   code: TEXT                                                                                                                                                              BusinessObj ects::
                                                                                                                                                           +     value:
                                                                                            -   codeSystem:                                                                                                                                                       FinalRandomizationAssignment
                                                                                                                                                           +     controlledName: PSMCodedConcept
                                                                                            -   codeSystemName: TEXT                                       +     businessProcessMode: PSMBusinessProcessMode                                                                                                                      BusinessObj ects::
                                                                                            -   codeSystemVersion: NUMBER                                                                                                                                                                                                              Waiv er
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BusinessObj ects::
                                                                                            -   displayName: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Adv erseEv entPlan
                                                                                            -   originalText: TEXT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     BusinessObj ects::
                                                                                            -   translation: SET{PSMCodedConcept}                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       ContingencyPlan
                                                                                                                                                                                                                                      Protocol Concepts::Constraint
                                                                                                                                                                                                                                                                                                                OStudy Design and Data Collection::
                                                                                                                                                                                                                                                                                                                  OEncounterDefinitionList--???

                                         BasicTypes::BRIDGStatus                                                                                                            BasicTypes::BRIDGContactAddr                                                                                                     +     listOfDataCollectionInstruments:
                                                                                «abstraction»                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        BusinessObj ects::
                               +     effectiveEndDate:                                                                                                     +     type: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Subj ectRecruitmentPlan
                                                                                                                                                                                                                                                                                                                                                                  Protocol Concepts::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           BusinessObj ects::SafetyMonitoringPlan
                               +     effectiveStartDate:                                                                                                   +     effectiveTime: BRIDGInterval
                                                                                                                                                                                                                                                                                                                                                                       Variance
                               +     statusValue:                                                                                                          +     usage: PSMCodedConcept                                                                               Protocol Concepts::
                                                                                                                                                                                                                              Protocol Concepts::
                                                                                                                                                                                                                               EligibilityCriterion                   ExclusionCriterion




                                                                                                                                                                                                                                                                                                     BusinessObj ects:
                                                                                                                                                                                                                                                                                                     :ProtocolRev iew
                                                                                                                                                                                                                                                                                                                                            Protocol Concepts::
                                                                                                                                                                                                                                                                                                     +   date:                                   Milestone
                                                                                                                                                                                                                                                                                                     +   result:
cd Comprehensiv e Logical Model




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                Design Concepts::Masking




                                                                                                                                                                                                                                                                                                                                                                        Clinical Trial Design
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       level:                                   Protocol
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       objectOfMasking (set):                  Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       procedureToBreak:                         Control
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       unmaskTriggerEvent (set):


                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  HasSubElements
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  «Period»
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Design Concepts::Element

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    -    Children: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Protocol Concepts::DesignCharacteristic                          Protocol                                                                                                                                                                                                -    epochType: EpochTypes

   Name:                   Comprehensive Logical Model                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +     synopsis:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Configuration
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Protocol                     +     type: test value domain = a,d,f,g




                                                                                                                                  Protocol Authoring
   Author:                 Fridsma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Concepts::                    +     summaryDescription:                                                                                                                                                                                                                   AbstractActivity                                                  hasScheduledEvents                                                              hasElements
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Scope                       +     summaryCode:                                                                                                                                                                                           Design Concepts::PlannedTask
   Version:                1.0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +     detailedMethodDescription:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     displayName: char[]
   Created:                7/22/2005 2:53:51 PM                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        +     detailedMethodCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Protocol                                                                                                                           -     whoPerforms: int
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     sequence: int
   Updated:                7/29/2005 2:33:32 PM                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Concepts::Bias
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     procDefID: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -     sourceText: char[]                                                                                                                SubjectEvent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 Design Concepts::Arm
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      Protocol Concepts::StudyBackground(w hy)                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Design Concepts::ProtocolEv ent




                                                                                                                                  and Documentation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    nameOfArm: char[]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    description: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -   parent: AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    hasElements                                                                                          -    plannedEnrollmentPerArm: char[]
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    summaryOfPreviousFindings: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -   eventType: ScheduledEventType                                                  -    randomizationWeightForArn: int
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    summaryOfRisksAndBenefits: PSMDescription                           Protocol Concepts::StudyObligation                                                                                                                                                                                                                                                                                                                                                                                                              -   studyOffset: PSMInterval
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               1                                                                                                                                                                         -    associatedSchedules: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    justificationOfObjectives: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -   studyDayOrTime: char
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    justificationOfApproach: PSMDescription                            +   type: ENUMERATED
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    populationDescription: PSMDescription                              +   description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForEndpoints: PSMDescription                              +   commissioningParty:                                                                                                    Design Concepts::                                Protocol Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForDesign: PSMDescription                                 +   responsibleParty:                                                                                                       Randomization                                                                                                                                                                                                        taskAtEvent                               tasksPerformedThisSchedule
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Concurrency
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForMasking: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +       minimumBlockSize:                                                                                                                                                                                                                                                                                            hasOngoingEvents
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForControl: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +    rationaleForAnalysisApproach: PSMDescription                                                                                                                                              +       maximumBlockSize:


                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               1..*

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          +correlativeStudy 0..*                                                                                                                                                                                                                                                                            Design Concepts::Ev entTask                                                                                                                                                hasArms
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Design Concepts::StudySchedule
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               BusinessObj ects::Study
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -   localFacilityType: LocalFacilityType                                                       -       Periods: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   startDate: Date                                +primaryStudy 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -   centralFacilitityType: CentralFacilitiyType                                                -       Tasks: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   endDate: Date                                                                                                                                                                                                                                                                                                                       -   eventID: OID                                                                                                                                       hasUnscheduledEvents
                                                                                                                                                                                                                                                                                                                                                                                                                                            BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -       TaskVisits: Set                                                                                                      SubjectEvent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 BusinessObj ects:                       +   type: PSMCodedConcept                                                                                                                                                                                                                                                                                                               -   taskID: OID
                                                                                                                                                                                                                                                                                                                                                                                                                                        ClinicalDev elopmentPlan                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                -       associatedArms: Set                                                               Design Concepts::UnscheduledEv ent
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   :Amendment                            +   phase: PSMCodedConcept                                                                                                                                                                                                                                                                                                              -   purposes: Set
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   randomizedIndicator: Text                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             -      eventType: UnscheduledEventType
                                                                                                                                                                                                                                                                                                                                                                                              -_DevelopmentPlan      *
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +   SubjectType: PSMCodedConcept                                                                                                                                 BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Activ itySchedule (the "how ",
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      "w here", "w hen", "w ho")
                                                                                                                                                                                                                                                                                                                                                                                                           BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          Protocol Concepts::StudyObj ectiv e(w hat)                                            +    description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                      IntegratedDev elopmentPlan
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     1                                                           +   description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +   intentCode: SET ENUMERATED
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +   objectiveType: ENUM{Primary,Secondary,Ancillary}                                                                                                                                                                                                       hasPurposes
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +   id: PSMID
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   «execution mode»                                                                                                                                                           Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                           *                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   StudyActiv ityRef




                                                 Clinical Trial
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               Scheduled Sub Activities
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   -      activityID: OID
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              0..*

                                                                                                                                                                                                                                                                                                                                                                                                                                                Protocol Concepts::StudyDocument                                                                                                                                  -source              1     1..*
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  objective                                  Protocol Concepts::Outcome
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   effectiveEndDate: DATETIME                                            BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Defined By
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    1..* -    description: BRIDGDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   version:                                                              ProtocolDocument                                                                                                                                                                                                                                             Design Concepts::Ev entTaskPurpose                                                                    BasicTypes::StudyDatum
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    ranking: OutcomeRank
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   author: SET                                                                                                                                                                                                                                                                       as Measured By
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    associatedObjective: Set                                                                                 -   isBaseline: boolean                                                                                -    complete: bool
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   effectiveStartDate: DATETIME                                                                                                                                                                                                                                                                                                                                                                                                          -    value: Value
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    analyticMethods: Set                                                                                     -   purposeType: PurposeType                                                                                                                                                             Defined By




                                                 Registration
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   ID: SET PSMID                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    asMeasuredBy: Set                                                                                        -   associatedOutcome:                                                                                 -    timestamp: timestamp                   isKindOf                                                                                                                                                    «ODM:ItemDef»
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   documentID:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    outcomeVariable:                                                                                                                                                                                                -    itemOID:                                                                                                                                                                   kindOf                 Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   type: ENUMERATED = formal plus non...                               BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             «abstract»
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    threshold:                                                                                                                                                                                                                                                                                                                                                    Design                                                  PlannedInterv ention
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   description: PSMDescription                                         ClinicalStudyReport
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   title:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   status: PSMStatus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               StudyActivityDef
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   confidentialityCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BasicTypes::AnalysisVariableInst
                                                                                                                                                                                                                                                                                                                                                                                                                                    +   businessProcessMode: PSMBusinessProcessMode                                                                                                                                                                                                                                                                                                                                                   associatedVariable
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            «ODM ItemData»                                             «ODM:ItemData»                         -    roleInAnalysis: RoleInAnalysisTypes                                                                                    kindOfActivityRelation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      Design Concepts::Observ ation                                    Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                         SubjectDatum
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               -   transactionType:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            CommunicationRecord
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   -   subjectID: int
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BasicTypes::StudyVariable

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -    OID: long
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  «ODM:ItemDef»
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -    Name: char
                                                                                                                                                                                                                                                                                                                                                                                                                                                     BusinessObj ects::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  -    unitOfMeasureID: OID
                                                                                                                                                                                                                                                                                                                                                                                                                                                    SupplementalMaterial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       PlannedObserv ation
                                                                                                                                                                                                                                                                                                                                                                                                                +source 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         -    minValid:
                                                                                                                                                                                                                                                                                                                                                                                           Entities and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -    maxValid:
                                                                                                                                                                                                                                                                                                                                                                                                                                         +     type:
                                                                                                                                                                                                                                                                                                                                                                                              Roles::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             -    controlledName: ENUM
                                                                                                                                                                                                                                                                                                                                                                                                                  +target 0..*           +     description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                         ResearchProgram                                                                                                                                                                                                                                                                                                                                                                                                                                          «ODM ItemData»                          «ODM:ItemData»
                                                                                                                                                                                                                                                                                                                                                                                                                                         +     version:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Design Concepts::                      Design Concepts::
                                                                                                                                                                                                                                                                                                                                                                                         +    type:                                      +     ID: SET PSMID
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               BasicTypes::RIMActiv ityRelationship                                                                                                                                                                                                                                               DiagnosticImage                       TreatmentConfirmed

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     relationshipCode: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     sequenceNumber: NUMBER
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     pauseCriterion:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     checkpointCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     splitCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     joinCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     negationIndicator: BOOLEAN
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +     conjunctionCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                 Entities and Roles::
                                                                                                                                                                                                                                                                                                                                                                                                                                         Study                                                                                                                                                                                                                                                 restates Objective
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Statistical Concepts::StatisticalConceptArea                                                                                          Statistical Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       BusinessObj ects::                                                                                                                                                                 StatisticalAnalysisSet
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                -     evaluableSubjectDefinition: char                                           hasAnalysisSets
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           *          *                                                                                                                                                              StatisticalAnalysisPlan
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                -     intentToTreatPopulation: char                                                                                       +     description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                             1..*                                                                                                                                                                                                                                                                                                                               -     clinicallyMeaningfulDifference: char                                                                                -     scopeType: AnalysisScopeTypes
                               Entities and Roles::Place                                        Entities and Roles::Entity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -     proceduresForMissingData: char
                           +       gpsText:                                                                                                                                                                                                                                                                                                                                                                                              1                                                                                                                                                                                                                                                                                                                                      -     statSoftware: char
                                                                                  +   instantiationType: ENUM {Placeholder, Actual}                                                                                                   Entities and Roles::Role                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     BasicTypes::ActActRelation
                           -       mobileInd: boolean                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -     methodForMinimizingBias: char                                                                                                                      hasCriteria
                                                                                  +   id: SET <PSMID>
                           -       addr:                                                                                            1                                                                                   * +                                                                                                                                                                   Entities and Roles::Activ ityRoleRelationship                                                                                                                                                                                                                                                                                                                                     -     subjectReplacementStrategy: char                                                                                                                                                                                                              -   description: BRIDGDescription
                                                                                  +   name: string                                                                                                                            id:
                           -       directionsText:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          hasHypotheses                       -     randAndStratificationProcedures: char                                                                                                                                                                                                         -   relationQualifier: BRIDGCodedConcept
                                                                                  +   code: PSMCodedConcept                                                                                                               +   code: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                          +    relationshipCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    -   mode: PSMBusinessProcessMode
                           -       positionText:                                  +   quantity: int                                                                                                                       +   name:
                                                                                                                                                                                                                                                                                                                                                                                          +    sequenceNumber: NUMBER                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               -   effectiveTime: BRIDGInterval
                                                                                  +   description: PSMDescription                                                                                                         +   status:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Statistical Concepts::AnalysisSetCriterion
                                                                                                                                                                                                                                                                                                                                                                                          +    negationIndicator: BOOLEAN                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           +   priorityNumber: NUMBER
                                                                                  +   statusCode: BRIDGStatus                       1                                                                                     +   effectiveStartDate:
                                                                                                                                                                                                                                                                                                                                                                                          +    time: TimingSpecification                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              -           description: char                                                                                 -   negationRule: AbstractRule
                                                                                  +   existenceTime: BRIDGInterval                                                                                                        +   effectiveEndDate:
                                                                                                                                                                                                                                                                                                                                                                                          +    contactMediumCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     -           subgroupVariable: StudyDatum                                                                      -   detail: char
                                                                                  +   riskCode: PSMCodedConcept                                                                                                           +   geographicAddress:                             1                                                                                                          * +    targetRoleAwarenessCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                               -           sequence: int                                                                                     -   sourceAct: AbstractActivity
                    Entities and Roles::Organization                              +   handlingCode: PSMCodedConcept                                                                                                       +   electronicCommAddr:
                                                                                                                                                                                                                                                                                                                                                                                          +    signatureCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       -   destAct: AbstractActivity
                                                                                  +   contactInformation: SET <PSMContactAddr>                                                                                            +   certificate/licenseText:
                                                                                                                                                                                                                                                                                                                                                                                          +    signature: PSMDescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            -   sequence: int
                   +   geographicAddress:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Statistical Concepts::HypothesisTest
                                                                                                                                                                                                                                                                                                                                                                                          +    slotReservationIndicator: BOOLEAN
                   +   electronicCommAddr:
                                                                                                                                                                                                                                                                                                                                                                                          +    substitionConditionCode: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             +   «property» relationQualifier() : PSMCodedConcept
                   +   standardIndustryClassCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               +   significanceLevel: double
                                                                                                                                                                                                                                                                                                                                                                                          +    id: PSMID                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +   «property» sourceAct() : AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                +   lowerRejectionRegion: int
                                                                                                                                                                                                                                                                                                                                                                                          +    status: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                        hasAnalysisSets
                                                                                                                                                                                                                                                 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +   upperRejectionRegion: int                                                                                                                                                                                                                                                       +   «property» destAct() : AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                           1..*                                                                                                                                                                                                                                                                                 +   testStatistic:                                                       hasAnalyses
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Statistical Concepts::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                +   comparisonType: AnalyticComparisonTypes
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       SampleSizeCalculation
                                                                        Entities and Roles::Liv ingEntity                 Entities and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          #   associatedSummaryVariables:
                                                                                                                         Roles::Material                                                                                                                                                                           Entities and Roles::Employee                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           +       clinicalJustification: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -source
                                                                       +   birthTime:
                                                                                                                                                                                                                                                                                                            +      jobCode: PSMCodedConcept                                                                                                                                                                                                      activity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 +target activity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             kindOfActRelation
                                                                       +   sex:                                          +   formCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                           -source
                                                                       +   deceasedInd: boolean                                                                                                                                                                                                                                                                                                                                                                            activity                                                                AbstractActivity
                                                                       +   deceasedTime:                                                                                                                                                                                                                                                                                                                                                                                                  1                                                                                                                                                                                                                                                                                                             kindOfAnalysis
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BasicTypes::RIMActivity
                                                                       -   multipleBirthInd: boolean                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             kindOfAnalysis
                                                                       -   multipleBirthOrderNumber: int                                                                                                                                                                                                                                                                                                                                                                                      +      businessProcessMode: PSMBusinessProcessMode                                                                                                                                                                                                                                                        -_StatisticalAnalysisSet      *
                                                                       -   organDonorInd: boolean                                                                                                                                                                                                                                                                                                                                                                                             +      code: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                         Statistical Concepts::
                                                                                                                                                                                                                                                                                            Entities and Roles::Patient
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Statistical Concepts::Hypothesis                                                                                                                                                                            StatisticalAssumption                                                                                        BasicTypes::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      derivationExpression: TEXT
                                                                                                                                                                                                                                                                                            +   confidentialityCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            AbstractRule
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      status: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                  AbstractActivity                                                            +     description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    +TerminatingActivity 1..*                                                                                                                                                    +   statement: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      availabilityTime: TimingSpecification                                                                                                                                                                                                                                               -_Hypothesis                                                                                                                                                                                                                                                     -     isExclusive: bool
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 -   associatedObjective:                                                                       Statistical Concepts::Analysis
                                                                                                                  Entities and Roles::          OProtocolStructure::                                                                                                                                                                                                                                                                                                                          +      priorityCode: PSMCodedConcept
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       *                                                                                         -   clinicallySignificantDiff: char                     *
                                                                                                                 ManufacturedMaterial            ElectronicSystem                                                                                                                                                                                                                                                                                                                             +      confidentialityCode: PSMCodedConcept                                                                                                                                                                                                                                                                     +    description: PSMDescription                                                                                                                                                                                                            +     run() : bool
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      repeatNumber: rangeOfIntegers               +EndEvent 1                                                                                                                                                                                                                                                  +    analysisType: Set{AnalysisTypes}
                                                                                                             -     lotNumberText: string                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           Protocol Concepts::StudyObj ectiv eRelationship                                                                                                                                                                                                                                                                     hasAssumptions
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              +      interruptibleIndicator: BOOLEAN                                                                                                                                                                                                                                                      hasAnalyses         +    analysisRole:
                                                                                                             -     expirationTime:                                                                                                                                                                                                                                                                                                                                                            +      uncertaintyCode: CodedConcept                                                                                                                                                                                                                                                                            +    rationaleForAnalysisApproach: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   +StartEvent 1                                                               +    type: PSMCodedConcept
                                                                                                             -     stabilityTime:                                                                                                                                                                                                                                                                                                                                                             +      reasonCode: PSMCodedConcept                                                                                                                                                                                                                                                                              #    associatedStrategy:
                                                                                                                                                                                                                                                                                  Entities and Roles::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              #    associatedHypotheses:                                                    hasModel                              Statistical Concepts::StatisticalModel
                                                                                                                                                                                                                                                                                         Access
                           Entities and Roles::Person
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    +FirstActivity 1..*
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      +           description: PSMDescription                                                                                implements          Implements           implements
                       +        geographicAddress:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             hasChildAnalyses                                                                                                         #           outputStatistic: StudyVariable
                       -        maritalStatusCode:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           computations: Set
                       -        educationLevelCode:
                                                                    Entities and Roles::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  hasStrategy                                                                 -           assumptions: Set
                       +        raceCode:
                       -        disabilityCode:                    NonPersonLiv ingEntity
                       -        livingArrangementCdoe:
                                                                   +   strain:
                       +        electronicCommAddr:
                                                                   -   genderStatusCode:                          Entities and Roles::Dev ice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  hasComputations
                       -        religiousAffiliationCode:
                       +        ethnicGroupCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             *                                                                                                                                                                                                                                                     Statistical Concepts::                                                                                                                                                             «implementationClass»            «implementationClass»                       «implementationClass»
                                                                                                         -       manufacturerModelName:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Design Concepts::                BusinessObj ects::                          Design Concepts::
                                                                                                         -       softwareName:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   SequentialAnalysisStrategy
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          TemporalRule                     BusinessRule                               ClinicalDecision
                                                                                                         -       localRemoteControlStateCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   AbstractActivity
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      alphaSpendingFunction:
                                                                                                         -       alertLevelCode:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    Statistical Concepts::Computation
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      timingFunction:
                                                                                                         -       lastCalibrationTime:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      analysis:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           description: PSMDescription
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            +      trialAdjustmentRule:
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   +IsContainedIn               +sourceActivity 1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         1..* +targetActivity                                                                                                                                                                                                                                                                                                                                                                                         -           algorithm: char
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           input: AbstractStatisticalParameter
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      -           output: AbstractStatisticalParameter




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         +contains 1                +generates 0..*
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  +passedTo

                                                                                                                                                                                                                                                                                                                                                                                                                                                                    OProtocolStructure::                             OProtocolStructure::                                                                                                                                                                                                                                                                                                                                                                                                                           hasSchedules
                                                                                                                                                                                                                                                                                                                                                                                                                                                                  ResponsibilityAssignment                           Activ ityDeriv edData
                                                                                                                                                                                                                                                                                                                                                                                                                                                       1




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              Plans::Protocol/Plan                                               BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        SiteSubj ectManagementProj ectPlan




                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Protocol activities and                                                                                                                                                                                                                                                                                                                                                                                                                  BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          1
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              1..*



                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          SiteStudyManagementProj ectPlan




                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Safety monitoring (AE)
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   SponsorStudyManagementProj ectPlan
                                                                                                  BasicTypes::BRIDGInterv al                                         OStudy Design and Data Collection::
                                                                                                                                                                                                                                                                                       BusinessObj ects:
                           BasicTypes::BRIDGBusinessProcessMode                                                                                                        OBRIDGDeriv ationExpression
                                                                                        -   startTime: timestamp                                                                                                                                                                               :
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             1 1..*
                                                                                        +   endTime: timestamp                                             +     type: ENUM{transformation, selection}                                                                                 RegulatoryRecord
                       +       modeValue: ENUM {Plan, Execute}
                                                                                                                                                           +     rule: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              BusinessObj ects::Inv estigatorRecruitmentPlan
                                                                                                                                                           +     id: PSMID
                                                                                                                                                           +     name: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     BusinessObj ects::
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 ClinicalTrialMaterialPlans


                                                                                                                                                                                                                                                                    BusinessObj ects::
                                                                                                                                                                OStudy Design and Data Collection::OBRIDGTransition                                              RandomizationAssignment                  BusinessObj ects::               BusinessObj ects::Guide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         BusinessObj ects::
                                                                                                     BasicTypes::BRIDGID                                                                                                                                                                                  EnrollmentRecord                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            DataMonitoringCommitteePlan
                                                                                                                                                            +    criterion: RULE                                                                                 +    randomizationCode:
                                                                                            +   source: Text                                                +    eventName: TEXT                                                                                 +    subjectID:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 BusinessObj ects::BiospecimenPlan
                                                                                            +   version: Text                                                                                                                                                    +    assignmentDateTime:
                                                                                            +   value: Text



                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      BusinessObj ects::




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Structured
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     DataManagementPlan
                                                                                                                                                                                    BasicTypes::BRIDGAnalysisVariable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            BusinessObj ects::AssayProcedures
                                                                                                BasicTypes::BRIDGCodedConcept
                                                                                                                                                           +     name: TEXT
                                                                                            -   code: TEXT                                                                                                                                                              BusinessObj ects::
                                                                                                                                                           +     value:
                                                                                            -   codeSystem:                                                                                                                                                       FinalRandomizationAssignment
                                                                                                                                                           +     controlledName: PSMCodedConcept
                                                                                            -   codeSystemName: TEXT                                       +     businessProcessMode: PSMBusinessProcessMode                                                                                                                      BusinessObj ects::
                                                                                            -   codeSystemVersion: NUMBER                                                                                                                                                                                                              Waiv er
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  BusinessObj ects::
                                                                                            -   displayName: TEXT
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  Adv erseEv entPlan
                                                                                            -   originalText: TEXT




                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Eligibility
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       BusinessObj ects::




                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       Statistical Analysis
                                                                                            -   translation: SET{PSMCodedConcept}                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       ContingencyPlan
                                                                                                                                                                                                                                      Protocol Concepts::Constraint
                                                                                                                                                                                                                                                                                                                OStudy Design and Data Collection::
                                                                                                                                                                                                                                                                                                                  OEncounterDefinitionList--???

                                         BasicTypes::BRIDGStatus                                                                                                            BasicTypes::BRIDGContactAddr                                                                                                     +     listOfDataCollectionInstruments:
                                                                                «abstraction»                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        BusinessObj ects::
                               +     effectiveEndDate:                                                                                                     +     type: PSMCodedConcept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             Subj ectRecruitmentPlan
                                                                                                                                                                                                                                                                                                                                                                  Protocol Concepts::                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           BusinessObj ects::SafetyMonitoringPlan
                               +     effectiveStartDate:                                                                                                   +     effectiveTime: BRIDGInterval
                                                                                                                                                                                                                                                                                                                                                                       Variance




                                                                                                                                                                                                                                                                                                                                                                                                                                                                     Determination
                               +     statusValue:                                                                                                          +     usage: PSMCodedConcept                                                                               Protocol Concepts::
                                                                                                                                                                                                                              Protocol Concepts::
                                                                                                                                                                                                                               EligibilityCriterion                   ExclusionCriterion




                                                                                                                                                                                                                                                                                                     BusinessObj ects:
                                                                                                                                                                                                                                                                                                     :ProtocolRev iew
                                                                                                                                                                                                                                                                                                                                            Protocol Concepts::
                                                                                                                                                                                                                                                                                                     +   date:                                   Milestone
                                                                                                                                                                                                                                                                                                     +   result:
Active Subprojects
– Trial design (Diane Wold, GSK and Peter Abramowitch,
  Fasttrack)
   • CDISC trial design subcommittee has moved their work into
     enterprise architect and UML modeling to speed the development
     efforts
   • Update the model every 2 weeks with results of teleconference
– Statistical design (Greg Anglin, Lilly)
– eDCI subproject (Don Kacher, Oracle, Christo Andonyadis,
  NCICB)
   • General purpose HL7 message to describe a data capture
     instrument, or case report form. Using HL7 “early adopter”
     mechanisms.
   • Actively using gForge documents, forums, webpages, and CVS
     repository
Active Subprojects

•   Clinical Registry message (Lakshmi Grama)
     – Development of an HL7 message for registering a clinical trial in a clinical
       trial repository
          • Eudract (europe)
          • Clinicaltrials.gov, PDQ
          • Traditional HL7 project development (not early adopter)
•   Adverse events (Joyce Niland, COH)
     – First significant submodel to be harmonized
     – Will lead to both application development and message specification
•   Harmonization branch and maintenance
     – New concepts/classes/definitions added from CTOM (Smita Hastak,
       ScenPro)
     – Cleaning up the model and definitions

•   Moving away from strict HL7 RIM classes – an emphasis on clarity in
    describing the domain
   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 for
      regulated clinical research TC (RCRIM)
    – BRIDG will serve as an integrator for CDISC message harmonization
    – Development of a clinical trials reference implementation based on BRIDG
      (CTOM, caAERS)
    – Establishing both organizational and procedures to maintain and grow the
      model

• This model will serve as the semantic foundation for data interchange
  specifications in HL7, CDISC, the NCI, and the clinical trials space of
  caBIG
Rich semantics captured in BRIDG

• CDISC glossary of terms
• Semantics and examples at the class and attribute
  level
• Datatypes help to clarify the semantics around the
  classes and attributes
Current Priorities

Static Structures
• Cleaning up the current model to make it more accessible to both
   domain experts and technical experts
• Development of a harmonizable analysis model of the CDISC SDTM
   (submission data tabular model)
• Harmonization of adverse events model from CoH, harmonization with
   HL7 Patient Safety SIG UML model(s)

Dynamic Structures
• Defining the Dynamic models at present
• Harmonize with COH dynamic models
• Linking dynamic structures to static structures

Developing processes to support collaboration, input into BRIDG and use
  of BRIDG
Work with Training Group to develop BRIDG educational
  “bootcamp” for domain and technical experts
Existing Standards Harmonization


Existing DMIM                               • Process A
                                               – Harmonize existing HL7
           A
                                                 DMIM for regulated clinical
                                                 research
                BRIDG model                 • Process B
                                               – “extract” domain knowledge
                                                 from existing messages and
           C                          C          systems into formal UML
                                                 models
UML submodel              UML submodel      • Process C
                                               – Harmonize and merge UML
                                                 models into BRIDG
           B                          B
                                      \

 Existing HL7             Existing object
  message                     model
New Message and Application Development


• Process D                      HL7 message                 UML loader
                                  generation                Semantic Cntr
   – Generate a “release” of
     BRIDG for formal
     requirements traceability
     with vetting within            DMIM                   Annotated UML
                                                               model
     stakeholder organizations
• Process E                                E                            F

   – HL7 message generation
     using HL7 mechanisms               BRIDG model release version X

• Process F
   – caBIG application                                      D
     development with
     annotation, semantic                       BRIDG model
     connector, UML loader
Tools to Support the People Process


• www.BRIDGproject.org
  – Open source
  – Used for projects like firefox and mozilla
  – Bug and feature tracking
  – Discussion forums
  – Source control with CVS check-in/check-out
  – Project administration
  – Email and listservs with notification of code, discussion
    group, or document changes
  – Ability to link and synchronize CVS repositories across sites
Working with VCDE


• The need for coded concepts and terminology within
  BRIDG
   – Can show some examples of these in the model
• Semantic harmonization at the analysis level
   – The difficulty of mapping ODM with RIM at the
     implementation level (CDISC experience)
• Integration at the implementation level requires
  terminology and vocabulary. However, to get there,
  you need to have shared semantics at the analysis
  level.
   – If the semantics are different at the analysis level, then they
     will map into different CDEs and terminologies at the
     implementation level.
Two places that we need VCDE


• Input into the model
   – make it easier to be consistent with existing standards (ie,
     HL7 datatypes?)
• Output from the model
•     (into semantic connector, UML loader, HL7
  message specifications, etc)
•     How do we construct good models that capture
  the domain expertise and can be used to drive
  application and message interchange development?
Discussion questions

• How do we work with VCDE ?
   –   Identification of best of breed coded concepts (SNOMED, etc)
   –   Development of new enumerated lists and code sets
   –   Setting Priorities for development?
   –   Best practice for model and terminology development
   –   How do we work with groups outside of caBIG?
        • HL7 defined value sets? caBIG defined value sets? Others?
• Input into the model
   – How do we develop “harmonizable models”?

• Output from the model
   – How do analysis models flow into caBIG tools?
   – Constrained models
Douglas B. Fridsma
fridsma@cbmi.pitt.edu
www.BRIDGproject.org
The goal: Constructing
Harmonizable Models

• “Semantically robust static and dynamic
  representations of the problem to be solved
  described in an implementation-independent
  way.”
Static Portions of the Model


  – *UML class diagram
     •   *Documentation of each class and all attributes
     •   *Bound to data types
     •   Candidate terminologies identified
     •   Other attribute value sets
     •   OCL business rules (could be structured text with OCL
         equivalence) For example, person class and credit card
         class – the person class might have a gender (MF) and the
         credit card class would have Mr/Mrs, there needs to be a
         rule that helps to disambiguate how the credit card class
         would manage this.
Dynamic Portions of the Model


•   *Process flow
•   *story boards
•   *Scenarios
•   *Use cases
•   *Text UML activity diagrams
•   *Links to static structures
•   Interaction diagrams (?)
•   Sequence diagrams
•   Collaboration diagrams (UML 2.0)
Examples


  –   Model A with entities and roles combined
  –   Model B with separation across moods
  –   Study as higher-level concept
  –   Protocol as higher-level concept
Interchange Standards:
Long-term Desired Outcomes



 • A holistic approach to standards, facilitating data
   interchange from sites through regulatory submission,
   utilizing XML
 • Standards for data acquisition supporting the population of a
   cross-trial warehouse within FDA
 • HL7-CDISC models harmonized to yield value for both
   clinical research and healthcare – sharing of information
   between EMR and clinical trials
 • Global adoption of CDISC data standards


                    CDISC Meeting with FDA Commissioner, April 2003
    Biomedical Research Integrated Domain Group
    (BRIDG) Model
•   A domain analysis model that reflects the domain space of clinical/biomedical
    research using language domain experts comprehend
•   Follows the HL7 Development Framework (HDF); led by HL7 RIM expert
•   Initiated in January 2004 by CDISC Board
•   Developed through numerous modeling and vetting sessions with domain
    experts from CDISC, FDA, and NCI/NIH
•   Is being „adopted‟ by the HL7 Regulated Clinical Research Information
    Management (RCRIM) Technical Committee and implemented at NCI
•   Now posted on an open website: www.bridgproject.org
•   A means of „bridging‟ together the clinical research standards within CDISC
    and between CDISC and HL7 (towards interoperability)
•   Has also „bridged‟ organizations
  CDISC and HL7:
  Why BRIDG?


                       Domain Anaysis Model or Problem Space Model (a la HDF)
Level of Abstraction




                                                        RIM


                                ODM
The BRIDG Model



•   What is it? A collaborative effort between CDISC, HL7, caBIGTM, NCI,
    FDA, and Industry to produce one common, shared data exchange
    standard
•   Vision: Create a domain analysis model for the clinical research domain
    to harmonize clinical research standards among each other and to
    harmonize standards between clinical research and healthcare
•   Key Goal: Define a structured computable protocol representation that
    supports the entire life-cycle of clinical trials protocol to achieve syntactic
    and semantic interoperability
Why BRIDG?



• Reduce costs; eliminate duplication of effort
• Facilitate data sharing
• Help to speed delivery of innovative solutions to the patient
  based on research
• Improve the efficiency and timeliness of data reporting
• Enhance patient safety during clinical trials
• Improve the shared care of patients
“Protocol” and the Semiotic Triangle


          Concept 1                                         Concept 2
      “We need to sign off on                           “Protocol XYZ has enrolled
      the protocol by Friday”                                  73 patients”




Thing 1                              Symbol                              Thing 2
Document                        “Protocol”                               Study



           Concept 3
                                                           Thing 3
    “Per the protocol, you must be
       at least 18 to be enrolled”                           Plan

                   Source: John Speakman/Charlie Mead
    The Communication Pyramid:
    Communicating complexity is HARD

•   How do you link the people who know about clinical domain (domain experts)
    with the technology implementers who will develop tools to support clinical
    work so that we have semantic interoperability?

•   The Problem Space (Domain Space)
     – A structured way to describe and document the information requirements of a
       particular area of interest
     – “What”
     – Discovered through Analysis
•   The Solution Space (Implementation/Technical Space)
     – “How”
     – Discovered through Design
     – One Problem  Many Solutions

•   The domain analysis model BRIDG is a bridge between domain experts and
    technical experts
The Communication Pyramid

                    BRIDG model

                   Non-standard Graphics


                     ad hoc Drawings


                  Structured Documents

                  Free-text Documents
                           `
                     Discussions


  Communication                Source: Charlie Mead, MD, HL7
         The BRIDG model update:
          How do I get involved?



Douglas B. Fridsma, MD, PhD
Center for Biomedical Informatics
Center for Pathology and Oncology Informatics
University of Pittsburgh
Update on activities since last meeting


• New URL for the BRIDG project
   – www.BRIDGproject.org
• Active participation from CDISC, pharmaceutical
  companies (GSK, Lilly, others), and industry
  (Fasttrack, Digital Infuzion, Oracle), caBIG (COH,
  UPMC, MSKCC, and others)
   – Committing real resources and time to the effort
   – A true collaboration with the various stakeholders in the
     effort
Technology


  – Still working on access control, roles, and supplemental tools
    to assist in the development effort
      • CVS repository – open up the process to other SIG and project
        leads, while protecting the “trunk” of the CVS tree
          – CVS_ACL vs subversion vs. other
      • Parallel HTML pages to augment those in gForge for individual
        subprojects
          – Sig and project maintained
      • PHP and wiki features to integrate into gForge for collaborative
        authoring of the model
          – Novel methods of disseminating the model
          – Trackers, Web pages, and downloads
      • Supporting subproject development with mailing lists, document
        management, and CVS access (TDM, eDCI)
Processes


• caBIG – testing subproject coordination and
  harmonization processes with eDCI, and TDM. Will
  harmonize caERS when it is ready.
• HL7 – multiple proposals about how to use BRIDG
  for message specification.
   – Harmonization of existing message specifications
   – Model management project at HL7
   – Development of new messages
• CDISC – harmonization of glossary with vocabulary
  and definitions in the model
Ways to participate


• HTML view of the model
   – www.bridgproject.org/model
   – Updated ever 110-14 days – represents the current active model
• Trackers
   – Modeled after HL7 Harmonization forms
   – Useful for smaller comments, definitions, suggestions
• Download the model from the CVS repository or file release
   – file release
   – CVS repository
• DBMS implementation (pending and testing)
• Active model development in subprojects
     How do I create an application based on
     BRIDG?

                             • We have checked in the
BRIDG trunk   Version 1
                               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.
     How do I create an application based on
     BRIDG?

                                    • The Harmonization branch is
BRIDG trunk     Version 1
                                      similar to a “bug fix” – it
                                      allows developers to break
                                      the model, fix things that
Harmonization   Version 1   V 1.1
branch
                                      need to be changed, and
                                      maintain versioning control
                                      while they do it.
     How do I create an application based on
     BRIDG?

                                       • When a team begins a new
BRIDG trunk     Version 1
                                         project to develop a
                                         message or application, they
                                         would check out the most
Harmonization   Version 1   V 1.1
branch
                                         recent version of the model
                                         that is currently developed.
                                         Typically this is the
                                         Harmonization branch.



eDCI
development                 eDCI 1.1
branch
     How do I create an application based on
     BRIDG?

                                                   • New projects will begin
BRIDG trunk     Version 1
                                                     in the same way –
                                                     checking out the current
                                                     version of the model
Harmonization   Version 1   V 1.1        V 1.2
branch
                                                     from the harmonization
                                                     branch
                                                   • We now have three
CAERs
                                       caERs 1.1
                                                     versions of the model,
development
branch                                               all working in parallel.
                                                   • Although EA helps with
                                                     synchronizing models,
eDCI
development                 eDCI 1.1    eDCI 1.2
                                                     there is no substitute for
branch                                               good coordination and
                                                     collaboration.
Support for subprojects


• Developing php-based webpages that can be
  maintained and customized by subproject leads
   – Limitation in gForge with project and subproject descriptions
• Developing less error-prone CVS access controls
   – check-in to CVS grants root access to the entire CVS tree
       • Subproject leads need flexibility in organizing the CVS tree to fit
         their needs
       • CVS root needs to be protected from inadvertent “check-in”
• Parallel constructs with documents, webpages, cvs
  repository, etc
   – TROVE map is too high-level, but need an “ontology” to help
     organize and find information on the gForge site.
   – Improved search capabilities?
     How do I create an application based on
     BRIDG?

                                                  • Development can continue
BRIDG trunk     Version 1
                                                    on both of these branches,
                                                    using the “master-replica”
                                                    features of Enterprise
Harmonization   Version 1   V 1.1      V 1.2
branch
                                                    Architect


CAERs
development
branch


eDCI
development                 eDCI 1.1   eDCI 1.2
branch
     How do I create an application based on
     BRIDG?


BRIDG trunk     Version 1                          Version 2   •   New projects will
                                                                   repeat the process of
                                                                   checkout, modeling,
                                                                   etc.
Harmonization   Version 1   V 1.1        V 1.2      V 1.3      •   As the development
branch                                                             continues, there will
                                                                   be periodic new
                                                                   “releases” of the
CAERs                                                              model.
development                            caERs 1.1 caERs 1.2     •    The arrow from
branch                                                             version 1 to version
                                                                   two represents some
                                                                   “vetting” of the model
                                                                   from stakeholders in
eDCI                                                               the project and
development                 eDCI 1.1    eDCI 1.2    eDCI 1.3       incorporation of
branch                                                             harmonization
                                                                   branch changes.
     How do I create an application based on
     BRIDG?

                • As a development
BRIDG trunk                                  Version 2                 Version 3
                  branch matures, it can
                  be merged with the
                  harmonization branch
Harmonization                                 V 1.3        V 1.3        V 1.3
branch
                  (using master-replicas)
                • The model then can be
                  “vetted” with the
CAERs
                  stakeholders, and a       caERs 1.2    caERs 1.3    caERs 1.4
development
branch            release generated


eDCI
development                                   eDCI 1.3     eDCI 1.2    eDCI 1.3
branch
                       Name:      ModelManagementProposal
                       Package:   ModelManagementProposal
                       Version:   1.0
                       Author:    Fridsma


HL7 Model management processes for vetting
 Readers (level 1)


                            Suggest model
                         modification or addition




                                    [Analysis
                                    incomplete]


                                                                                         [NO vote]
                            Create proposed
                         modification or addition
Modelers (level 2)




                             [Harmonization Incomplete]



                     [Analysis Complete]
Stewards (level 3)




                         Harmonize modification                                 Accept modification
                               proposal                                                               Check modification into
                                                     [Harmonization complete]       proposal                  CVS




                                                                                                                     [YES vote]
munity (RCRIM)




                                                                                                                modification consensus
     How do I create an application based on
     BRIDG?


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

                             • A portion of the BRIDG
BRIDG trunk   Version 3
                               model will need to be
                               annotated and modified for
              Annotated        the constraints of the
                model          semantic connector and
                               UML loader
                                – Future releases may accept
                                  a broader range of
                                  relationships
     How do I create an application based on
     BRIDG?

                                        • The output of the processes
BRIDG trunk   Version 3
                                          related to the semantic
                                          connector and UML loader
              Annotated                   will be used for application
                model                     development


caCORE        Semantic       UML
tools         Connector     Loader




Application
Module                    Application
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
   – Adopters/developers trying to figure out what it means for
     them
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
• The best way to move forward is to start seeing what
  works, (and what doesn‟t) and have the flexibility to
  adapt to new requirements to the process and
  technology
Current ongoing project

•   eDCI message
     – Participants: Oracle, caBIG, CDISC and others
     – developing an HL7 message that describes electronic data collection
       instruments (case report forms)
•   Clinical Trial Registration message project
     – Participants: caBIG, CDISC, HL7, Eudract, clinicaltrials.gov, PDQ
     – Developing a clinical trial registration message
•   Adverse events application development
     – Participants: caBIG, COH
     – Developing an adverse events reporting system
•   Trial Design modeling
     – Participants: caBIG, CDISC, FastTrack, others
     – Extending the trial design portions of the model in BRIDG
•   Statistical modeling extensions
     – Participants: CDISC, Eli Lilly, other pharma, FastTrack
     – Extending the statistical modeling portions of the model
Clinical Research Back Office: The
motivation for integration




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posted:7/23/2011
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