BRIDG Update January HL7 Working Group Meeting 15 January

BRIDG Technical Harmonization Committee (THC) Members Charlie Mead Smita Hastak Bron Kisler Steve Sandberg Becky Angeles Wendy Ver Hoef Lewis Frey 2

BRIDG Update Overall status BRIDG Vocabulary SDTM BRIDG Review Team Education 3

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, or device on a human, animal, or other biologic subject or substance plus all associated regulatory artifacts required for or derived from this effort.

BRIDG: Recent Significant Progress NCI is standardizing on the BRIDG as basis for semantic interoperability in the CTMS Workspace CDISC’s Trial Design and SDTM standard are now represented in BRIDG 5

Release 2.0 Plan – 1 Release 2.0 scheduled for April 2008 R2.0 new content: AE, C3PR (NCI’s Patient Registry) Full binding of all static attributes to HL7 V3 data types Candidate terminology lists/value sets (drawn from existing standards if possible) for all attributes bound to ‘coded concept descriptor’ data types Consolidation of ‘business process pillars’ in the model with guideline of > creating the RIM problem of ‘duplicitous attributes.’ 6

Release 2.0 Plan - 2 Introduction of formal business rules as class invariants using both free text and equivalent parsable OCL statements Representation of ‘player/scoper’ semantics Complete mapping of BRIDG Model static attributes to the HL7 RIM Test evaluation of strategy for incorporating BRIDG Model ‘sub- domains’ (e.g. cancer-specific semantics, TB semantics) using NCI’s CTOM Creation of more exemplary instance diagrams (e.g. AE content, SDTM IG, etc.) 7

Recent BRIDG Infrastructure Changes Current in-progress model available on Gforge site (access via Look on Gforge site for bug and enhancement trackers Look for BRIDG news on Gforge site Project mapping spreadsheets will be owned and maintained by project teams rather then the BRIDG THC. So, these spreadsheets will no longer be published with each release. BRIDG THC will publish the first mapping from BRIDG to RIM. 8

9 BRIDG Vocabulary

10 BRIDG 1.0 Vocabulary Oct-Nov / NCI EVS Team conducted thorough analysis of BRIDG 1.0 “Parent Classes” and “Attributes” and aligned with NCI Thesaurus concepts / definitions (256 items assessed) A few discrepancies were noted that needed to be resolved by BRIDG THC (e.g., Sex vs. Gender, Participant vs. Study Subject) BRIDG 1.0 has been loaded into caDSR

11 BRIDG 2.0 Vocabulary - 1 BRIDG 2.0 “Parent Classes” and “Attributes” need to be aligned with NCI Thesaurus concepts BRIDG 2.0 will include “vocabulary binding” for attributes with CD data types (approx. 400 value sets total) Categorize as…(1) CDISC developed; (2) NCI developed; (3) other known Controlled Vocabulary; or (4) needs to be developed

12 BRIDG 2.0 Vocabulary - 2 CDISC and NCI value sets identified to be aligned with BRIDG = 84; value sets still requiring work = 308 (Note: some value sets are shared across BRIDG attributes, such as targetSite) BRIDG 2.0, including vocabulary binding, to be released and implemented in caDSR in April NCI internal timelines require value sets to be defined at a faster pace than the current CDISC / RCRIM vocabulary process

SDTM BRIDG Mapping Report to RCRIM Diane Wold January 15, 2008

SDTM Harmonization with BRIDG Some UML modeling of SDTM in 2005 & 2006, but model quite different from BRIDG Release 1.0 During harmonization discussions summer 2007, we decided it would be more useful to map from the domain tables in the SDTMIG – SDTMIG contains content beyond SDTM itself – More accessible to SDTM users Did not include areas to be covered by other groups (e.g., AE, Trial Design) Mapping from SDTM to BRIDG is included in BRIDG Release 1.1

SDS Team Review of Mapping Goals – Check accuracy with a wider group of domain experts – Increase BRIDG knowledge in SDS Team Method – For each SDTMIG domain, build a UML class diagram including relevant classes – Use notes to show mappings – Record issues, questions, and comments

Status of Review Demography completed Lab completed – Chosen because it includes most SDTM Findings variables Vitals Signs completed (very similar to Lab) ECG, Physical Exam and Questionnaires being reviewed as a group – Chosen to cover remaining Findings variables – Comparisons to lab to ensure consistency, speed review Interventions not yet reviewed Events not yet reviewed – Since AE not mapped, review will be limited

Issues Identified by Review Corrections to mapping, many at datatype level – Example: COUNTRY mapped to “value” within AD datatype; should map to “country” Corrections to BRIDG – Example: StudyReferenceDateRange meant to represent SDTM RFSTDTC, but definition was inaccurate. Issues for SDS team – Example: SDTM IG allows two different uses for PEBODSYS, result of coding or pre-specified category; review group recommended eliminating the latter. Points to be clarified with other standards (Lab, RCRIM aECG) – Example: Is method of assay part of Lab model?

Review Team Benefits Appreciation of UML and of datatypes Disciplined modeling approach clarified areas of “gut level” uneasiness – Overloading of variables, such as PEORRES (can contain either an observation or an assessment as NORMAL) – Handling of assessments by different mechanisms in different domains (INTP a test in ECG but NORMAL a result in PE) Explaining issues to THC led us to better document how SDTM results variables are populated

Lab results flow LBORRES populated Are there units? Sponsor places original units In LBORRESU Is result numeric? Sponsor performs unit conversion Sponsor places converted measurement in LBSTRESC and LBSTRESN Original units = standard units? Sponsor copies LBORRES into LBSTRESC and LBSTRESN Sponsor places standard units in in LBSTRESU Is there a text standardization for this test? YES NO YES Sponsor performs standardization of text Sponsor places standardized text in LBSTRESC YES NO YES NO Assumption: a test cannot have both a text standardization and units. NO Sponsor copies LBORRES into LBSTRESC Sponsor copies LBORRES into LBSTRESC and LBSTRESN Assumption: for a test with units, the sponsor has identified units to standardize on

“Had we but known…” Starting with BRIDG might have avoided SDTM problems During development of Microbiology domain, we realized we were using “method” variable for both method of assay and method of specimen collection SDTM includes overloaded fields such as PEORRES and DSDECOD (COMPLETED or reason for non- completion) We were slow to realize that TESTCD may not uniquely identify a test. E.g., a lab test may also require specimen and method. This issue now requires metadata solutions.

Conclusions No show stoppers identified by review of SDTM mapping Any new SDTM domains developed must be mapped to BRIDG CDISC standards handle datatypes differently; issue needs to be addressed Use of BRIDG seems to be fulfilling promise of harmonizing standards, also improving their quality

BRIDG Education 23

Unified Modeling Language Used in the BRIDG model The industry-standard language for specifying, visualizing, constructing, and documenting the requirements of software systems The BRIDG model uses these UML diagrams: – Class diagrams – Activity diagrams – Instance 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 relationship multiplicity

The Pillars of Interoperability Necessary but not necessarily sufficient Common model across all domains of interest Foundation of rigorously defined data types Methodology for interfacing with controlled vocabularies Formal process and tools for defining interchange structures Source: Charlie Mead, MD, HL7

Foundation of rigorously defined data types Simple vs Complex Simple: Character, String, Text, Numeric

Datatypes: Simple vs Complex

R1 Important Content Concepts Planned, Scheduled, Performed Study ObservationResult vs. Assessment Analysis and Reporting

The BRIDG Backbone Classes Person Organization Material StudyProtocol Documentation Activity ActivityRelationship ObservationResult ObservationResultRelationship Assessment

A look at the model 32