Genomics Reporting Implementation Guide, published by HL7 International / Clinical Genomics. This guide is not an authorized publication; it is the continuous build for version 3.0.1-SNAPSHOT built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/HL7/genomics-reporting/ and changes regularly. See the Directory of published versions

Pharmacogenomic Reporting

Building a Pharmacogenomic Report: An Example

This section provides a walk-through of mapping from an example Pharmacogenomics (PGx) report to FHIR using the structure definitions and guidance defined in this IG. The PGx report is represented as a Genomic Report. The related observations and other resources are available as links in the table at the bottom of this section. The JSON representation of this report can be found here.

A PGx report focuses on the impacts of a patient’s genetics to the behavior of medications, and can provide recommended adjustments to medication based on these impacts. The intention of this page is to provide a “User Guide”, based on a specific report example, highlighting how the defined profiles can be used together to encode important relations in PGx reporting. The report and images for this guide are built upon work done by the eMERGE (Electronic Medical Records and Genomics) program, funded by the National Human Genome Research Institute (NHGRI). The Clinical Genomics Working Group has worked closely with eMERGE to integrate community feedback from their initial mapping into this PGx user guide.

Ordering a Pharmacogenomic Test

In order to receive a PGx report, you must first order a PGx test. Genomic tests, like all laboratory tests, are ordered using the Service Request resource. The example report in this section is based on a pre-coordinated gene panel defined by the sequencing laboratory. As such, the “code” element on the PGx report aligns with a pre-coordinated “code” element on the corresponding ServiceRequest, though the laboratory may provide additional codes as well. Additional structure may be in scope for the report if additional “orderDetail” data are present in the Service Request or if supporting information such as current medications are available during generation. An overview of the general relationships involved in ordering a report and receiving the results can be found here.

<ServiceRequest xmlns="http://hl7.org/fhir">
 <id value="eMERGEServiceRequest"/>
 ...
 <intent value="order"/>
 <code>
   <coding>
     <system value="http://example.org/hgsc.bcm.edu/lab-test-codes/"/>
     <code value="emerge-seq-ngs-pnl"/>
   </coding>
 </code>
 <subject>
   <reference value="Patient/CGPatientExample01"/>
 </subject>
 <specimen>
   <reference value="Specimen/GenomicSpecimenExample01"/>
 </specimen>
</ServiceRequest>

How to use the Report Mapping Images

The guide is based on three figures. Figure 1 is an overview of the components of a PGx report. Figure 2 is a schema describing the use of the components from the HL7 Clinical Genomics WG Implementation Guide, and figure 3 is an example report with each element of the report mapped to the schema in figure 2. Use the numbers in each figure to find where the section/element goes. For example, #7 in figure 1 is information about the performing lab. In figure 2, #7 indicates an instance of the Organization Resource for the performer which would be a link through the performer element in the Genetics Diagnostic report. In figure 3, #7 indicates specific information about the performing lab found in the sample report. Thus, the specific performing lab information in figure 3 maps to an instance profile of Organization Resource linked to the Genetic Diagnostic report (#7 in figure 2).

In addition to the numbers, the colors in Figure 1 are intended to help guide the grouping of information in the report.

These images should provide you with a clear understanding of how the various FHIR PGx resources may be used when constructing a PGx report.

Example Schema for PGx Reporting

The Schema below depicts a “decomposition” of the PGx FHIR resources used to construct the example report. The color coding and numbers in the schema are mapped via the legend (image above) to the detailed PGx report shown in Figure #3.

This PGx report, like all genomic reporting, is packaged with the diagnostic report profile. It conveys metadata about the overall report via the genomic study profile and carries multiple “result” Observations. All of the observation findings may “hang” directly off of the Genomic Report.

All pharmacogenomic implications are intended to be communicated using components within the Therapeutic Implication profile. The Medication-assessed component of the Therapeutic Implication profile, is the place to communicate the medication whose implication is being described, including a place for the coded value of the medication. Because this is an international profile, no guidance is provided on the medication coding system to be used. Instead, the appropriate code system for the jurisdiction, can and should be used.

To associate a Therapeutic-implication instance with a proposed recommended action (e.g., discontinuing a medication, altering dosage, or “choose alternative medication”) one can use the Medication Recommendation, potentially with a MedicationStatement instance. Use RelatedArtifact in Therapeutic-implication to supply additional or supporting information, such as CPIC guidelines. In this report example, the text which explains the methodology of the test, was modeled using the PlanDefinition resource (#5 in the schema). The clinical genomics work group has not yet determined the value of providing a profile on PlanDefinition, and requests community feedback on encoding testing methodology details.

Creating the Example FHIR PGx Report

In the example used in this User Guide, the PGx results are based on diplotypes (star alleles), and the underlying variant observations, found in each relevant PGx gene that is covered by the PGx gene panel. These diplotypes are then used as a basis for relating PGx gene-drug knowledge implications. Note that there was also the choice in this use case, to derive Implication statements from one or more genotype Observations and not from variants directly.

Below is one of the therapeutic implications in the report:

<Observation xmlns="http://hl7.org/fhir">
...
 <extension url="http://hl7.org/fhir/StructureDefinition/workflow-relatedArtifact">
   <valueRelatedArtifact>
     <type value="citation"/>
     <url value="https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/"/>
   </valueRelatedArtifact>
 </extension>
 <code>
   <coding>
     <system value="http://hl7.org/fhir/uv/genomics-reporting/CodeSystem/tbd-codes-cs"/>
     <code value="therapeutic-implication"/>
   </coding>
 </code>
 <derivedFrom>
   <reference value="Observation/Pgx-geno-1002"/>
   <display value="CYP2C9*1/*1"/>
 </derivedFrom>
 <derivedFrom>
   <reference value="Observation/Pgx-geno-1003"/>
   <display value="VKORC1 rs9923231 C/T"/>
 </derivedFrom>
 <component>
   <code>
     <coding>
       <system value="http://loinc.org"/>
       <code value="51963-7"/>
     </coding>
   </code>
   <valueCodeableConcept>
     <coding>
       <system value="http://ncimeta.nci.nih.gov"/>
       <code value="C0043031"/>
       <display value="warfarin"/>
     </coding>
   </valueCodeableConcept>
 </component>
 <component>
   <code>
     <coding>
       <system value="http://hl7.org/fhir/uv/genomics-reporting/CodeSystem/tbd-codes-cs"/>
       <code value="therapeutic-implication"/>
     </coding>
   </code>
   <valueCodeableConcept>
     <system value="http://loinc.org"/>
     <code value="LA25391-6"/>
     <display value="Normal Metabolizer"/>
   </valueCodeableConcept>
 </component>
 <component>
   <code>
     <coding>
       <system value="http://hl7.org/fhir/uv/genomics-reporting/CodeSystem/tbd-codes-cs"/>
       <code value="conclusion-string"/>
     </coding>
   </code>
   <valueString value="This individual is homozygous for the normal allele for the CYP2C9 gene. Based on the genotype result, this patient is predicted to have normal CYP2C9 function. This individual is also heterozygous for the variant allele for the VKORC1 gene. Expression level of the VKORC1 gene is associated with warfarin sensitivity. Based on the genotype result, this patient is predicted to have medium sensitivity to warfarin."/>
 </component>
</Observation>

The following table contains additional information regarding the profiles used in mapping this example PGx report to FHIR, as well as individual example instances

This Artifact List provides a comprehensive listing of the FHIR artifacts defined as part of the Genomics Implementation Guide and may be helpful when developing the PGx report.

Mapping to eMERGE III FHIR Template

Notable changes from the eMERGE III FHIR Template docs include:

1. Scope - this example focuses on the PGx panel within the eMERGE report and does not include a separate diagnostic panel.
2. Extensions - the eMERGE ‘summary interpretation text extension’ is now supported through an Observation component. The eMERGE usage of the ‘report disclaimer text extension’ is not included in our example but is seen by the ‘X2’ label in the figures.
3. Medication Recommendation - the original eMERGE spec did not structure medication recommendation proposals, which were left in plain text comments.

For further information about the eMERGE Program, see: Pre-Print Journal Article: “Genomic Considerations for FHIR; eMERGE Implementation Lessons” and eMERGE Network Website.