1. 1 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update JOINT RCRIM and CG Session CTLAB Message Pharmacogenomics Results Overview

2. 2 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update Joint RCRIM and CG AGENDA PGx History CTLAB Overview Overview of Genetic Variation Model Overview of Gene Expression Domain Analysis Model Next Steps PGx CTLAB Rel 2 Status and Normative path

3. 3 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update Pharmacogenomics History HL7 Clinical Genomics WG Established as a SIG in 2003 Includes members from clinical practice and clinical research Focus on V2 and V3 (Common Message Elements [CMET]) genetic and genomics data models V3 Genetic Models Single Gene (Genetic Locus) CMET Draft Standard for Trial Use – May 2005 (Revised May 2006) Multiple Gene (Genetic Loci) CMET Draft Standard for Trial Use – Jan 2007 Unified Full Genetic Variation CMET Draft Standard for Trial Use – Jan 2008 Normative – Jan 2010

4. 4 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update Pharmacogenomics History (cont.) Genetic Variation V2 message Developed for clinical practice to carry findings from a lab to a physician, genetic councilor, etc. Subset of full V3 model, focus on interpretive, not raw (sequence) data Genetic Variation V3 Reduced CMET Companion to V2 message HL7 Clinical Statement compliant (payload for O&O Lab) Gene Expression Model Intended for V2 and V3 implementation Domain Analysis Model balloted Sept 2009

5. 5 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update CTLAB Overview Based on CDISC LAB Model First CDISC model converted to HL7 Based on CDISC version 1.0.1, but fully implements version 1.1 Designed for bulk (daily, weekly, monthly) transmission of lab test results from a lab to a clinical trial sponsor HL7 History Passed DSTU Ballot in October 2003 Passed Normative Ballot in May 2005 Implementation Guide Balloted Jan 2006 ISO Standard in August 2007

6. 6 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update Genetic Variation Overview Presented by Amnon

7. 7 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update Pharmacogenomics Directions V3 Genetic Variation Updated IG for CMET by May 2010 Additions to Support Complex Disease Genotyping. Extend Domain Analysis Model for Genetic Variation, Date TBD V2 Genetic Variation Additions to Support Complex Disease Genotyping. Gene Expression V2 IG and V3 CMET expected by May 2010 Re-ballot enhanced GE DAM by May 2010 Specimen Handling Initial work started – mapping to NCI, LOINC and SNOMED

8. 8 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update CTLABR2 Structure and Status Based on CTLAB Version 1 Designed for bulk (daily, weekly, monthly) transmission of genetic testing results from a lab to a clinical trial sponsor Designed to carry genetic raw and low granularity data under an SDTM suite of domains (as with ECG data) Additions to Core Model Consent to Genotype Act Some Specimen Handling (Collected to DNA/RNA) Call for the Genetic Variation CMET(s) Passed First DSTU Ballot May 2006 Modified May 2007 for multigene CMET Tested with Drug Metabolism and Cancer Gene Data

9. 9 HL7 Jan 2010 Working Group MeetingsCTLAB Pharmacogenomics Update CTLABR2: Get to Normative Required Upgrade CMET Call for Normative Genetic Variation CMET Use genomic choice box currently consist of GV future includes GE Add Genetic Specific Content to BRIDG (CTLAB already there) Complete vocabulary development and binding for non-CMET elements Desirable Harmonize Specimen Handling with O&O Lab CMET Follow Ups Upgrade Implementation Guide Longer Term Upgrade for Gene Expression CMET(s) Upgrade for Microorganism Genotyping (Viral and Bacterial) Upgrade or clone/modify to allow animal subjects for CDISC SEND support