BRIDG Basics

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

How did BRIDG get started? Four important streams of development came together CDISC: In early 2004, CDISC started constructing a Domain Analysis Model to support harmonization of their standards for clinical research as well as with the Health Level Seven (HL7) healthcare standard. NCI: In late 2004, NCI's Cancer Biomedical Informatics Grid (caBIG™) initiative joined the CDISC BRIDG efforts to construct a structured protocol representation for its Clinical Trials Management Systems (CTMS) Workspace, in order to further interoperability among clinical trials research in cancer. HL7: In 2005, the BRIDG model was adopted by the HL7 Regulated Clinical Research Information Management (RCRIM) Technical Committee as the RCRIM Domain Analysis Model. FDA: In 2007, the US Food and Drug Administration included BRIDG in their 5 year IT Plan as a foundation for several projects.

BRIDG Scope BRIDG Scope: Protocol-driven research and its associated regulatory artifacts, i.e. the data, organization, resources, rules, and processes involved in the formal assessment of the utility, impact, or other pharmacological, physiological, or psychological effects of a drug, procedure, process, subject characteristic, biologic, cosmetic, food or device on a human, animal, or other subject or substance plus all associated regulatory artifacts required for or derived from this effort, including data specifically associated with post-marketing adverse event reporting.

BRIDG Governance BRIDG Board of Directors BRIDG Semantic Coordination Committee

Current Governance of the BRIDG Model BRIDG Board of Directors FDA HL7 CDISC Academia NCI Pharma Industry BRIDG Board of Directors BRIDG Board of Directors Representation from the current stakeholders Helps to set priorities and identify resources Source: Doug Fridsma

BRIDG Board of Directors Appointed Members Charlie Mead NCI Bron Kisler CDISC Chuck Jaffe HL7 Jay Levine FDA At Large Members Term Expiration Becky Kush* 2011 John Speakman 2013 Jack Jones Cecil Lynch 2012 AbdulMalik Shakir Diane Wold Sub Dubman 7 * Chair

Current Organization of the BRIDG SCC CDISC caBIG HL7 FDA BRIDG Semantic Coordination Committee Semantic Coordination Committee (SCC) Responsible for ongoing model maintenance Harmonizes subdomain projects into the main model Source: Doug Fridsma

Semantic Coordination Committee (SCC) Name Affiliation Charlie Mead NCI / Booz & Company Steve Sandberg NCI / ScenPro, Inc. Mike Woodcock NCI / Mayo Clinic Smita Hastak Wendy Ver Hoef Becky Angeles Julie Evans CDISC Lloyd McKenzie NCI / Gordon Point Informatics 9 9

The BRIDG Model

Perspectives of BRIDG Canonical Perspective Domain Analysis Model (DAM), comprehensive UML model with packages for each sub-domain SME Perspectives Domain friendly business models, separate UML model for each sub-domain Adverse Event Common Protocol Representation Regulatory Study Conduct Ontological Perspective (Future) Model used for semantic validation and inferencing, several OWL-DL representations HL7 Perspective Formal binding to the HL7 RIM, central DMIM-like diagram with supporting diagrams, modeled in HL7 v3 graphical style

Perspectives of BRIDG Recognize and support the different types of BRIDG users Each perspective is intended for a different audience Each perspective is a representation of the same semantics

BRIDG Canonical Perspective Comprehensive Domain Analysis Model (DAM) Intended for information analysts Single UML model Modeled and managed in Enterprise Architect

BRIDG Canonical Perspective Model of Subject

BRIDG Comprehensive View – Canonical Perspective Common Protocol Representation Study Conduct Adverse Event Regulatory

BRIDG SME Perspective Domain-friendly layer Intended for the subject matter experts (also called business users or domain experts) Multiple UML models, one for each sub-domain Modeled and managed in Enterprise Architect Automatically generated from Canonical Perspective

BRIDG SME Perspective Adverse Event Sub-Domain Model of Subject

BRIDG HL7 Perspective RIM-based model Intended for message developers Modeled in HL7 proprietary modeling methodology and developed in Visio Single DMIM-like model Maps to UML-based model Manually generated from Canonical Perspective

BRIDG HL7 Perspective Model of Subject

BRIDG Semantic Perspective Several ontological representations OWL-DL format Intended for semantic validation and inferencing

BRIDG Semantic Perspective Model of Subject

BRIDG as a global, public standard CDISC Review and Comment Process resulted in BRIDG as a CDISC standard in January 2010 ISO Joint Initiative Council (JIC) Ballot Process – first round in May 2010 – BRIDG passed the ballot in both ISO and HL7 – next round starts in December 2010 ISO HL7 CDISC

(starting with most recent release) BRIDG Content – 1 (starting with most recent release) Release Project Stakeholder R3.0.3 Clinical Data Acquisition Standards Harmonization (CDASH) V1.1 CDISC Study Data Tabulation Model (SDTM) V3.1.2 Integrated Case Safety Report (ICSR) R2 FDA R3.0.2 caBIG® Central Clinical. Participant Registry (C3PR) v2.9 NCI Cancer Adverse Event Reporting System (caAERS) v2.2 Patient Study Calendar (PSC) v2.6 LabViewer v2.2 R3.0.1 Clinical Trials Registration and Results HL7 RCRIM R3.0 (Architecture Redesign only)

BRIDG Content - 2 Release Project Stakeholder R2.2 CDISC HL7 Message Study Design (partial) FDA CDISC HL7 Message Study Participation R2.1 Clinical Trial Registry (COPPA, ct.gov, WHO, PRV1.0) CDISC, NCI Protocol Abstraction (COPPA – Correlations, Organizations, People and Protocol Abstraction) NCI R2.0 Adverse Events CDISC, NCI, NIH, US Federal Gov’t, FDA Player / Scoper for Person and Org NCI, CDISC Patient Registry (C3PR) R1.1 Study Data Tabulation Model (SDTM) CDISC Trial Design Model R1.0 Regulated Product Submission (RPS) FDA/HL7 RCRIM Patient Study Calendar (PSC) Clinical Trial Object Model (CTOM) caXchange/LabHub NCI/HL7RCRIM TC/CDISC

A Bit More About the Canonical and SME Perspectives

Unified Modeling Language Used in the BRIDG model via a modeling tool called Enterprise Architect The industry-standard language for specifying, visualizing, constructing, and documenting the requirements of software systems The BRIDG model uses these UML diagrams: Class diagrams Instance diagrams State transition diagrams

UML Class Diagrams class – a concept of primary importance the domain-of-interest, depicted as a rectangle labeled with the concept’s name attribute (including datatype specification) – a descriptive feature of a class, depicted as being contained within the class relationship – one of several types of “lines” between classes

Class diagram example class attribute data type relationship multiplicity data type

BRIDG Class: StudyProtocolVersion

BRIDG Class Definition: StudyProtocolVersion

Definition of designConfigurationCode attribute

Instance Diagrams “Instances” of class diagrams use sample data values to illustrate specific representational constructs

Part of an Instance Diagram

State Transition Diagrams A State Transition Diagram illustrates how an element (often a Class) can move between states, classifying its behavior according to transition triggers and constraining guards. Also called State Machine Diagrams or State Charts

State Transition Diagram – Study Subject

Important Components of a Release The Model UML Based Model in Enterprise Architect Model Sub-Domains and Comprehensive View RIM Based Model Users Guide and Release Notes Change Lists Mapping Spreadsheet

User’s Guide

User’s Guide Section 1: Guide to the Reader Section 2: Executive Summary Section 3: The BRIDG Project and BRIDG Model Section 4: The BRIDG Model: General Considerations and Representational Conventions Section 5: Model Content Section 6: Glossary Section 7: Appendix

Release Notes Table of Contents 1 Executive Summary 1.1 BRIDG ISO Joint Initiative Council (JIC) Ballot 1.2 BRIDG Definition 1.3 BRIDG Project Stakeholders 1.4 BRIDG Project Goals 1.5 Definition of BRIDG Model Domain of Interest 2 What’s New in Release 3.0.1 2.1 General changes in Release 3.0.1 2.2 Detailed Change Lists for Release 3.0.1 3 Files in R3.0.1 Package 3.1 UML-Based Models 3.2 RIM-based Models 3.3 Report of Comprehensive UML-Based Model 3.4 XMI of Comprehensive UML-Based Model 3.5 Release Notes (this file) 3.6 User’s Guide 3.7 BRIDG Domain Analysis Static Model Style Guide 3.8 BRIDG CDISC Comment Resolution Spreadsheet 4 Known Issues

UML-based Model: Mappings to Source Projects Enterprise Architect

UML-Based Model Mappings to Source Projects RTF Report methodCode public :CD A coded value specifying the technique that is used to perform the procedure.For example, for a specimen collection, finger stick, veni puncture, Abdominal/ ascites effusion, Biopsy, Bronchial alveolar lavage (BAL), etc.For example, if procedure is cholecystectomy the method could be open or laparoscopic. Map:CTOM = 'SpecimenAcquisition.methodCode' Map:Lab = 'SpecimenCollection.method' Map:SDTM IG = 'EG.EGMETHOD' Map:SDTM IG = 'LB.LBMETHOD'

Foundation of rigorously defined data types Simple vs Abstract Simple: Character, String, Text, Numeric BRIDG uses ISO 21090 data type specification

Datatypes: Complex ISO 21090: Healthcare Data Types ST = String CD = Concept Descriptor (Coded Concept) DSET = unordered collection, unique values ED = Encapsulated data URG = Uncertain Range RTO = Ratio II = Instance Identifier Some CD properties: displayName originalText code codeSystemName codeSystemVersion valueSet And more

Interfacing with Controlled Vocabularies Plans to move BRIDG semantics into a controlled environment such as NCI’s EVS / caDSR BRIDG controlled vocabulary should integrate with existing stakeholder vocabulary

Project Team involves BRIDG SCC early What’s the Process? Project Team develops Domain Analysis Model, mapping spreadsheet, valid value lists Project Team involves BRIDG SCC early Reps from project team meet with SCC to harmonize the project model into the BRIDG Updated BRIDG Domain Analysis Model is created The project to BRIDG mapping spreadsheet needs to be maintained

A Look at the Model in Enterprise Architect How to get to the version for review: http://www.cdisc.org/contentmgr/showdetails.php/id/1938 How to get to the model on the internet www.bridgmodel.org The gForge site: Release Files News Bug and enhancement trackers Work in progress in Subversion

www.bridgmodel.org

A Look at the Model in Enterprise Architect How to open the model and look at basic components Project Browser Views Class diagrams State Transition Diagrams Instance diagrams

Enterprise Architect – Project Browser

Project Browser - Views

Protocol Representation View

Comprehensive View

Project Browser – State Transition Diagrams

Project Browser – Instance Diagrams