FHIR Genomics:What You Need to Know for

Project Implementations

® Health Level Seven and HL7 are registered trademarks of Health Level Seven International, registered with the United States Patent and Trademark Office.

Grant WoodIntermountain Precision GenomicsIntermountain Healthcare

Gil AlterovitzAssistant ProfessorHarvard Medical School/Boston Children's Hospital

® Health Level Seven and HL7 are registered trademarks of Health Level Seven International, registered with the United States Patent and Trademark Office.

2007, 2013 - Family Health History or Pedigree

model

2009 to 2013 - Genetic Variation model and

Cytogenetics model for laboratory reporting of

genetic test results to the EHR

2011 to 2013 - Clinical Document Architecture

(CDA) Genetic Test Results electronic document

2014 and beyond – Fast Health Information

Resource (FHIR) for both family health history

and genetic/genomic testing

HL7 Standards

Use Cases/Workflows Published: “HL7 Domain Analysis Model: Clinical Genomics”

Specimen Identification + Germline testing for biomarkers/mutations (usually inherited) + Tumor testing for biomarkers/mutations (somatic / tumor specific) +Pediatric Testing + Prenatal Testing + Infectious Disease Testing + Emerging Specimen scenarios + Microbiome analysis of the patient + Free-cell cell-free circulating tumor DNA (ctDNA) + Cell-free fetal DNA (cffDNA) + Clinical Sequencing – Germline Testing + Description of Primary Clinical Sequence Workflow – Germline Testing + Alternative Germline Workflows + Alternative Flow 1: Chart Review + Alternative Flow 2: New Genetic Knowledge + Alternative Flow 3: New Clinical Indication + Cancer Profiling – Somatic Testing + Description of Primary Clinical Sequence Workflow – Somatic Testing + Alternative Workflows – Somatic Testing + Alternate Workflow 1: Referral + Alternate Workflow 2: Pathologist Ordered Testing + Decision Making Tools – Family History and Drug Dosage Calculators + Public Health Reporting + Description of Public Health Reporting Scenario + Cancer Registry workflow + Clinical and Research Data Warehouses + Cytogenetic Marker identification via sequencing +Pharmacogenomics + Description of Scenario + Pharmacogenomics – Somatic Profiling + Pharmacogenomics – Germline + Primary Germline Pharmacogenomics Germline Testing Workflow + Alternate Germline Pharmacogenomic Workflow – Pharmacist Involvement + State & Regional Health Information Exchanges (HIE) + Human leukocyte antigen (HLA) Typing + Summary of Challenges + Background on NMDP + HML and HL7 + Additional Use Case Scenarios (from Sep 2016) + Bone Marrow Report + Rare/Undiagnosed Diseases+ Preimplantation Testing + Fetal Testing – Cell-free DNA-Based Noninvasive Prenatal Testing + Newborn Screening + Current Newborn Screening +Alternative Research-Based Newborn Screening + Newborn Genome and Targeted Panel Testing + Public Health Testing – Microbial

Published 2018

Some Key Use Cases

Pharmacogenomics

Precision Cancer

Family History

HLA Typing

NGS Assay Evaluation/Regulatory

Germline and somatic sequencing for drug selection, rejection, dosing

Somatic (tumor) sequencing for diagnosis/prognosis

disease risk using germline tests, family pedigree, and clinical data

Immunogenomic sequencing for organ matching, pharmacogenomics, etc.

Benchmarking NGS quality of vendor to “gold standard”

Potential next steps

• Implementation details for HL7 Domain

Analysis Model (DAM): Clinical Genomics

– Describe implementations of use cases

– FHIR Genomics code examples for supporting use

cases

FHIR Genomics Vision

Unified Clinical and Genomic Data Standard

Modern Technology

Workflow Ready

clinical data genomics (omics) precision medicine

web-friendly RESTful resource-based

queryable granular on-demand

The “Unified” FHIR Specification

PayorArtifacts

GenomicsArtifacts

EHR Clinical DataArtifacts

FHIR ArtifactsResources

+ Profiles + Extensions

PACSArtifacts

AdminArtifacts

Clinical Data

Clinical Data

SequencingLab

EHRSystem

Research Data

WarehouseAll of Us Cohort Program, etc.

National Standard for Clinical Care & Research

SMART Apps

Clinician & Patient

FHIRGenomic Data

Clinical Care

Research

SMART on FHIR SMART on FHIR

FHIRFHIR

Genomic Data

Genomic Data

Clinicogenomics

Pharmacogenomics

Cancer Genomics

Precision Medicine

…

FHIR Genomics and Connectathon Projects

Demonstrated the feasibility of integrating a cloud-based PGx CDS system with a

commercial EHR, leveraging FHIR and the new CDS-Hooks decision support standard

Extended the PGx CDS service - When the service is triggered by a medication order

in the EHR, it queries the genomic repository for variants in the related pharmacogene,

which are returned in FHIR Genomics format

Where the gene has been sequenced, the genomic repository will perform real-time

extraction of variants from VCF and feed them to a VCF-to-FHIR translator

The translator performs real-time conversion into corresponding FHIR objects within

the FHIR Diagnostic Report to be returned

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But, Piloting is different from Testing in Connectathons

Piloting features:

• Longer feedback loop/cycle time

• Enables real-world data/on-site testing

• Multiple levels of interaction and scoping

• Enables multiple industry stakeholders to work

together, give/receive feedback

Landscape of Adoption Programs and Iterative Genomics Standard Feedback

Genomics Standard, Use Cases, Tools, and Processes

Pre-production and transitioning to production

SMART/FHIR Genomics Pilots

FHIR Genomics Connectathons

Utilize standard Feedback to standard

Genetic Test: MolecularSequence + Codes

+ External Data

GenomicsProfiles/

IG

SMALL

kilobyte DNA or RNA or AAMolecularSequence

DiagnosticReport

FamilyMemberHistory

Observation

Full Sequence Source – eg, GA4GHBIGterabyte

Germline / Somatic

Genomics Reporting Implementation Guide

MolecularSequence1

ObservationGenotype

Observation

Haplotype2

Observation

Haplotype1

Observation

Variant2

Observation

Variant1

DiagnosticReport

Genomics Report

Multiple Observations: Genetic Findings, Implications, Interpretations, Regions Studied

MolecularSequence2

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General Genomic Reporting Guidance and examples for the general structure of genomic reports, how to report overall interpretations and how to report genotypes, haplotypes and different types of variants. This content will be leveraged by all genomic reporting implementations.

Sequenced variants Guidance on expressing information about variants gleaned from various sequencing approaches including direct sequencing, shotgun sequencing, array-based testing, etc.

Cytogenomic Reporting Guidance on expressing information gathered by [[cytogenomic - link TBD]] testing techniques including FISH tests, chromosomal analysis, etc.

Pharmacogenomic Reporting Additional guidance and examples related to genetic testing done for the purpose of assessing genetic variations' impact on the use of medications - both for oncology and for general patient treatment

Somatic Genomic Reporting Additional guidance related to genetic testing done on somatic (non-germline) tissues, including assessments of tumors

Genomic Profiling for Transplantation Additional guidance related to genetic testing done for transplant match assessments, including HLA typing

Implementation Guide – Major Topics

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SMART on FHIR with Genomics

Genomics Lab

EMR

FHIRGenomics

Data

FHIRDiagnostic

Order

OrderPanel orSequencing

1

2 ReturnData Results

3 Send Data to Clinicogenomic App

SMART on FHIRClinical + Genomics Data

Incremental Adoption

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+ Additional Genetic Information

+ Location/Quality Information

Genetics LabTest Results

+ Whole Sequence/Reads

+ Context

Observation + Codes

Observation IG Genomics Profiles

MolecularSequence Resource

+ Repository Reads

+ Family History/Other Resource Profiles

Traditional Labs

NGS Labs

Consortium for Agile Genomics -

Approach

• Engage organizations (e.g. industry, academia, and

NGOs, etc.) interested in integrating precision

medicine/genomics into their workflows.

• Leverage expertise in the DAM use cases to help foster

an ecosystem for FHIR implementations in precision

medicine/genomics with guiding principles and

implementation codes for those use cases.

• Serve as an umbrella for taking various pilot programs

and their pilot "graduates" to next steps

Example: Genomics Levels

Receive Basic Genetic Results

● Observation genomics profiles (dealing with interpretations)

Receive Basic Genetic Reports with Context

● Diagnostic Report genomics profile

● Observation genomics profiles (dealing with discrete variants)

● Family History genetics profile

Order Genetic Tests

● Service Request

● Specimen resource

Reference Detailed Sequence Information

● MolecularSequence resource

(Quality metrics and linking to raw information)

Advanced Precision Medicine Integration● Rest of Observation genomicsprofiles (including complex variants)

● Support for at least one other resource related to

precision medicine (e.g. NutritionOrder, RiskAssessment)

Level 1: Bronze

Level 2: Silver

Level 3: Gold

Level 4: Platinum

Level 5: Diamond

Now

Recruit industry partners

Undertake efficient collaboration

Share results with HL7 and other organizations

GA4GH Genomics Toolkit

HL7 partners with the Global Alliance for Genomics and Health

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Use cases

FHIR Genomics data and sharing

Industry is piloting FHIR Genomics

Moving forward to next steps

Summary

FHIR Genomics:What You Need to Know for

Project Implementations

Questions