BRIDG Model: A Comprehensive Information Model for Biomedical Research

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

2. CDISC Mission The mission of CDISC is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.

3. Future of CDISC Models Future Uniform CDISC Standard Harmonized with HL7 Operational Data Interchange & Archive: ODM, LAB Submission Data Interchange & Archive: SDTM, SEND, ADaM • Data Sources • Site CRFs • Laboratories • Contract • Research • Organizations • Development • Partners • Operational • Database • Study Data • Audit Trail • Metadata • Submission • Data • CRT/Domain Datasets • Analysis Datasets • Metadata Protocol ODM = Operational Data Model SDS = Submission Domain Standards LAB = Laboratory Data Model ADaM = Analysis Dataset Models SEND = Std. Exchg. Non-clinical Data Standard Protocol Representation and Terminology

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

5. CDISC Roadmap Timeline

6. CDISC Standards Harmonization Operational Data Interchange & Archive: ODM, LAB Submission Data Interchange & Archive: SDS, ADaM SEND • Data Sources • Site CRFs • Laboratories • Contract • Research • Organizations • Development • Partners • Operational • Database • Study Data • Audit Trail • Metadata • Submission • Data • CRT/Domain Datasets • Analysis Datasets • Metadata BRIDG: Harmonizing to THE CDISC Standard Protocol ODM = Operational Data Model/Std SDS = Submission Domain Standards LAB = Laboratory Data Model/Std ADaM = Analysis Data Models SEND = Standards for the Exchange of Non-Clinical Data

7. Why BRIDG?

8. Interchange vs Interoperability Syntax  StructureSemantics  Meaning • Main Entry: in·ter·op·er·a·bil·i·ty: ability of a system ... to use the parts or equipment of another systemSource: Merriam-Webster web site • interoperability: ability of two or more systems or components toexchange information and to predictably use the information that has been exchanged. • Source: IEEE Standard Computer Dictionary: A Compilation of IEEE Standard Computer Glossaries, IEEE, 1990] Semanticinteroperability Syntacticinteroperability (interchange) Source: Charles Mead, MD, HL7

9. Computerized doesn’t mean syntactic interoperability 6 1 5 2 3 4

10. Concept 1 Concept 2 “We need to sign off on the protocol by Friday” • “Protocol XYZ has enrolled 73 patients” Thing 1 Thing 2 Study Document Concept 3 Thing 3 “Per the protocol, you must be at least 18 to be enrolled” Plan Semantic interoperability: “Protocol” and the Semiotic Triangle Symbol “Protocol” Source: John Speakman/Charlie Mead

11. Semantic Interoperability • To understand the data being received you must know both: • The definition of each element of data, and its relationship with each of the other elements • you must have a semantic model of the data and • The terminology to be used to represent coded elements, including the definitions, and relationships within the terminology Source: HL7

12. The Pillars of (Semantic) InteroperabilityNecessary but not Sufficient • Common model across all domains-of-interest • The representation of clinical trials in BRIDG • Model grounded on robust data type specification • Common data elements (ISO 11179) in the cancer Data Standards Repository (caDSR) • Methodology for binding terms from concept-based terminologies • Enterprise Vocabulary Server, terminologies • A formally defined process for defining specific structures to be exchanged between machines, i.e. a “messaging standard” • HL7 and implementation specifications • CDISC standards development process • caBIG unified process/model driven architecture

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

14. So how did BRIDG get started? • Two important streams of development that have been brought together into a collaborative framework • CDISC – 2003, started constructing an analysis model to map ODM standards to HL7 • NCI – 2004, started caBIG initiative to construct a structured protocol representation and interoperability among clinical trials research in cancer

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

16. caBIG and the Development of Structured Protocol Representation • Spring 2004 – kick-off of the caBIG project • University of Pittsburgh award the contract to develop a structured protocol representation to support clinical trials

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

18. Current Organization of the BRIDG project FDA HL7 • BRIDG Advisory Board • Representation from the current stakeholders • Help to allocate priorities and identify resources • Assist with vetting the model in the various constituents • Technical Harmonization Group • Responsible for ongoing model maintenance • Developing shared harmonization processes • Multiple subdomain projects • Representation from pharmaceutical companies, technology companies, government agencies, and cancer centers CDISC caBIG NCI PhRMA BRIDG Advisory Board CDISC caBIG HL7 BRIDG Technical Harmonization Group

19. Study calendar (caBIG) BRIDG model EudraCT FastTrack Protocol Authoring & Trial Design SDTM (CDISC) SDTM (CDISC) CONSORT (cancerGRID) Protocol Registration CTOM (caBIG) WHO ODM (CDISC) JANUS (IBM) Clinical Trials Operations HL7 (M Walker) PDQ ClinicalTrials.gov SDTM (CDISC) Adverse Events JANUS (IBM) caAERS (caBIG) SDTM (CDISC) LabSpecification FDA (M. Walker) caBIG NCI Lab SIG (caBIG) HL7 (M Walker) eDCI Oracle CTLab std (CDISC) CDISC ODM BRIDG projects and contributors

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

21. Model organization • Dynamic View • Captures the business process decomposition of the lifecycle of clinical trials research

22. Behavioral Aspects of BRIDG

23. Behavioral Aspects of BRIDG Roles are defined in the swim lanes with examples drawn from discussions with the domain experts

24. Behavioral Aspects of BRIDG The activities are described in activity diagrams that can be drilled down to provide additional detail. These are linked to the static (logical) portions of the model

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

26. Current Classes in Core Elements

27. Harmonized BRIDG elements

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

29. Epoch Arm Arm segment Example: Dissimilar Arms Screen Run-In Treatment Follow-up Trt Phase 1 Trt Phase 2 Follow-up Screen Run-In Standard Care Follow-up Source: Diane Wold - GSK

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

31. CT Registration message

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

34. DCI Definition (aka CRF)

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

36. SDTM Class Diagram

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

38. caAERS

39. Harmonization

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

41. Models in the staging area

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

43. CTOM BRIDG - Implementation Independent Domain Analysis Model Implementation Specific Models caAERS • Lab SIG Model • Study Calendar SIG Model • Financial SIG Model

44. CTOM BRIDG - Implementation Independent Domain Analysis Model Implementation Specific Models caAERS • Lab SIG Model • Study Calendar SIG Model • Financial SIG Model

45. CTOM BRIDG - Implementation Independent Domain Analysis Model Implementation Specific Models caAERS • Lab SIG Model • Study Calendar SIG Model • Financial SIG Model

46. Harmonized BRIDG elements Observation Classes from CTOM and SDTM

47. CTOM and SDTM harmonization (work in progress)

48. Harmonizing attributes

49. Adding tags to provide semantic traceability (and notes)

50. Simple semantic can be tracked in tagged values