Clinical Genomics Work Group (HL7) Mukesh Sharma Washington University in St. Louis June 16, 2011

Agenda Clinical Genomics Work Group WG Meeting Ballot Cycle Overview of Activities Omics Domain Analysis Model Gene Expression DAM Genetic Test Report (GTR) Implementation Guide Cytogenetics LOINC Codes Canonical Pedigree project Future Activities Useful Links

The HL7 Clinical Genomics (CG) Work Group Established as a SIG in 2003 Mission This group supports the HL7 mission to create and promote its standards by enabling the communication between interested parties of the clinical and personalized genomic data. The focus of clinical genomics work is the personalization (differences in individual's genome) of the genomic data and the linking to relevant clinical information. This Work Group will facilitate the development of common standards for clinical research information management across a variety of organizations -- including national and international government agencies and regulatory bodies, private research efforts, and sponsored research -- and thus the availability of safe and effective therapies by improving the processes and efficiencies associated with regulated clinical research

CG Work Group Leadership (Co-Chairs) Joyce Hernandez Merck & Co. Inc. Kevin Hughes MD Partners HealthCare System, Inc. Amnon Shabo, PhD IBM Mollie Ullman-Cullere Dana-Farber Cancer Institute

Formal Relationships with Other HL7 Groups CG Work Group coordinates with a large number of other Work Groups in order to accomplish its mission. Strongest relationships are with Orders and Observation Clinical Statement Clinical Decision Support Regulated Clinical Research Information Management Patient Care Electronic Health Records Modeling and Methodology Structured Documents

WG meetings/Balloting Cycles 3 times annually January, May, September meetings (past meetings) January 17–22, 2010 meeting at Pointe Hilton Squaw Peak, Phoenix, AZ May 17-20, 2010 meeting at Windsor Barra Hotel and Congressos, Rio De Janerio, Brazil October 3-8, 2010 meeting at Cambridge, MA January 9-14, Cliftons Meeting and Training Center, Sydney, Australia May 15-20, Lake Buena Vista, FL meetings (future meetings) September 11-16, San Diego, CA

Clinical genomics Work Group Meeting June, 2011 Update

8 Normative DSTU Informative v3:  Family History (Pedigree) Topic  Genetic Variations Topic  Gene Expression Topic  CMETs defined by the Domain v2: v2 Implementation Guides * The IG “Genetic Test Result Reporting to EHR” is modeled after the HL7 Version Implementation Guide: Orders And Observations; Interoperable Laboratory Result Reporting To EHR (US Realm), Release 1 CDA:  A CDA Implementation Guide for Genetic Testing Reports Common:  Domain Analysis Models for the various topics  A Domain Information Model (v3) describing the common semantics  Semantic alignment among the various specs Three Tracks: Overview of Activities

Mission and Charter Update Group is reviewed and updated its Mission and Charter Updated text is available at Updates to keep up with changes and include other Omics technology To emphasize on the genomic data generated for an individual. To emphasize on the need to achieve common semantics across the clinical and research domains.

Model presentations The workgroup invited speakers to present the following model. BRIDG Model LS DAM v 2.2 Model These models will inform the future modeling activities by the group.

Omics Domain Analysis Model Project Scope This is the -OMICS Domain Analysis Model project. This model will be used to develop our informational requirements for CMETs that support several –omics technology or specialty areas such as genetic variation, gene expression, proteomics, viral genetics, cytogenetics etc. Project Need Our initial DAM was part of the Gene Expression CMET project. During our initial modeling efforts we recognized the need to add a "generic" layer to our model that would represent concepts that are common to multiple –omics technologies as well as allow integration of clinical results. By including these classes it will facilitate extension of the model to support other technologies. Project Approval Approved by both Steering Division and the Technical Steering Committee (TSC) in February, 2011 Models will be located in HL7 GFORGE, meeting minutes and other supporting documents in HL7 WIKI. GFORGE: Wiki:

Gene Expression DAM May, 2010 Ballot Reconciliation Negatives from : CDISC, NCI, FDA and Siemens Received 16 Negatives and 30 Affirmative votes during ballot including negative comments from IRWG. The response to comments is available at - (Document links at the bottom of the page) Response to IRWG comments- This has resulted in participation of some HL7 team members with NCI's Generic Assay project. HL7 CG team will review results in a conference call with our NCI colleagues with HL7 CG team. It is felt that bringing the model into HL7 and tailoring it's use within the -omics DAM to support processes needed by the HL7 CG team will address the ballot points. We will revisit the points in the summarized comments and word document to inform the revision of the -omics DAM.

Genetic Test Report (GTR) Implementation Guide The Clinical Genomics and Structured Documents Work Groups jointly developed a CDA Implementation Guide (IG) for genetic testing reports. The GTR IG was balloted as Draft Standard for Trial Use in October, 2010 Ballot comments were addresssed by group from last ballot. Balloted as Draft Standard for Trial Use in May 2011 meeting. The updated IG is available at PT_R1_O2_2011MAY.pdf PT_R1_O2_2011MAY.pdf

Cytogenetics LOINC Codes Background CG has a Genetic Variation Implementation Guide that covers genetic mutations located within a gene. Need to report larger genetic changes found in cytogenetic testing. Develop LOINC codes for representing cytogenetics test results Develop prototype V2 interface based on the LOINC panel structure In Intermountain Healthcare’s DEV environment Potentially real/live interface between ARUP Laboratories and Intermountain Healthcare

Cytogenetics LOINC Codes Status The LOINC codes for cytogenetics result reporting that were officially submitted for approval by LOINC were included in the latest LOINC database, version 2.34, released on Dec. 29, Three panels (total 43 codes) Chromosome Analysis G Banded Panel Chromosome Analysis FISH Panel Chromosome Analysis Microarray Copy Number Change Panel Additional 11 codes Drafting HL7 V2 Implementation Guide for Cytogenetics Sample messages, etc. Detailed data models and associated terminology are created in Intermountain Healthcare’s development environment Developed cytogenetics section of the CDA Genetic Test Report (GTR)

Canonical Pedigree project Technical Steering Committee approved its project scope statement in January Project is intended to improve adoption of the standard V3 pedigree message. It has three aspects: Reference Pedigrees: Provide reference pedigree messages with corresponding text descriptions of the family history. Intended to be a resource for family history collection software verification. Interoperability Testing: The internal storage of a pedigree is up to the host system. Furthermore, some interoperability standards want to represent a pedigree using alternate formats (e.g. CCD, vMR, clinical statements, etc.). The canonical pedigree project shall provide test guidance to verify that host systems and alternate formats are able to accurately maintain the relationships in the reference pedigrees. If full fidelity cannot be maintained, the guidance will help quantify the lost of fidelity. Clinical Power: Many systems provide support only for simplified family histories. For example, they will capture that there were two instances of aunts with breast cancer. That simplified perspective is in contrast with one that maintains maternal vs. paternal line, the number of available aunts and clinical details such as age of onset. The intent behind this facet of CPP is to quantify the clinical benefits of improving the granularity of family and clinical histories.

Future Activities Specimen CMET: Update to Specimen CMET in order to represent CG use cases. Omics DAM: Review LSDAM and create Omics DAM by leveraging LS DAM components. Gene Expression CMET update Specimen CMET and LSDAM comparison: Review additions for suggestions to LSDAM.

Useful links HL7.org HL 7 Wiki Clinical Genomics Wiki HL7 Standards HL7v3 Ballot Site ICR (IRWG) comments on CG Gene Expression DAM Clinical genomics Oct 2010 Meeting Slides ations

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