Pharmacogenomic Medication Alerts and CDS Integration

For Pharmacogenomic use cases, results from genomic testing may indicate that certain treatments are contraindicated. For example, in CYP2C19 testing, it may be identified that a patient is a poor metaboliser of certain medications which require activation through the CYP2C19 enzyme. This includes Clopidogrel, meaning other antiplatelet therapy may need to be considered.

The UGR will not explicitly record prescribing implications for medications (as many could be affected by a gene variant), instead recording details of the genetic testing, such as genotype or phenotype, including metaboliser status, which is then assessed at the point of prescribing against the medication being considered, using applicable computable pharmacogenomic guidelines.

There are multiple resources which are relevant to proposed or prescribed medication alerts. However, each resource type has a different use case, as detailed below:

Purpose Resource Notes
Genomic fact Observation Used to record the information obtained directly from genomic testing, e.g. genotype, independent of any specific medication or clinical interpretation
Persistent patient warning or prescribing consideration Flag Used to highlight information which should be prominently visible across care settings, such as reduced efficacy, abnormal metaboliser status, or increased toxicity risk
Specific prescribing conflict DetectedIssue Result from a Clinical Decision Support service, which evaluated the underlying genomic finding against a concrete, proposed medication, using available clinical guidelines, at the point of prescription (likely embedded in external CDSS)
Actual adverse reaction AllergyIntolerance / AdverseEvent Recording of allergies or adverse reactions, generally post medication administration, to warn of effects. Generally recorded within the core patient/primary care record. MAY reference genotype as a contributing factor to adverse events

A snippet of a Flag resource for warning of a poor metaboliser status (impacting prescribing of clopidogrel) is provided below, with key elements populated. Usage of the Genomic finding itself is more future-proof as it can be applied to multiple drugs, as such direct drug related warnings will not be included within the UGR without clinical review. Instead the PGx result/flag SHOULD be taken into consideration alongside the rest of a patient's clinical circumstances and made available to CDSS, which in turn will alert or inform a prescriber:

{
  "resourceType": "Flag",
  "id": "Flag-Clopidogrel-Example",
  "extension": [
    {
      "url": "http://hl7.org/fhir/StructureDefinition/flag-detail",
      "valueReference": {
        "reference": "Observation/Observation-CYP2C19Metaboliser-Example",
        "display": "CYP2C19 poor metaboliser phenotype"
      }
    }
  ],
  "status": "active",
  "category": [
    {
      "coding": [
        {
          "system": "http://terminology.hl7.org/CodeSystem/flag-category",
          "code": "clinical",
          "display": "Clinical"
        }
      ]
    }
  ],

  "code": {
    "coding": [
      {
        "system": "http://snomed.info/sct",
        "code": "738786005",
        "display": "Cytochrome P450 family 2 subfamily C member 19 poor metabolizer"
      }
    ], 
    "text": "CYP2C19 poor metaboliser. Consider alternative antiplatelet therapy to Clopidogrel"
  },
  "subject": {
    "identifier": {
      "system": "https://fhir.nhs.uk/Id/nhs-number",
      "value": "9999999999"
    }
  },
  "period": {
    "start": "2026-07-27"
  },
  "author": {
    "identifier": {
      "system": "https://fhir.nhs.uk/Id/ods-organization-code",
      "value": "X26"
    }
  }
}

Flag lifecycle

Flag creation

A flag is created when the need for an alert on the patient record is identified. This may be at the point of reporting, where the genomic findings and implications are returned to the requesting clinician, or when the requesting clinician has reviewed the report and identified the need for an alert. Alternatively, this could be created when CDS identifies an issue at the point of prescribing (though this could equally be represented through a DetectedIssue resource).

Flag updating

The only updates to flags are expected to be setting a status of inactive, and adding of a period.end, though this is expected to be very rare, as the underlying genomic findings will remain the same, though implications may change as PGx guidance is updated. As such it is not expected that a Flag originating from genomic findings would naturally expire. Any organisation MAY update a Flag as part of routine care for a patient.

New Flags may be created to replace ones that are no longer valid or need to be superseded. Equally Flags may be withdrawn by marking them as entered-in-error, though this is expected to be rare.

CDS-Hooks

CDS-Hooks is a hook-based pattern for invoking decision support from within a clinician's workflow.
The API supports:

  • Synchronous, workflow-triggered CDS calls returning information and suggestions
  • Launching a user-facing SMART app when CDS requires additional interaction

When a triggering event occurs, CDS services receive workflow-specific context and service-specific data, (which may be provided through pre-fetch templates). The CDS service then return one or more "cards" containing information, suggestions, or links.

For pharmacogenomics (PGx) warnings, the FHIR resources provided as prefetched data to the CDS service are expected to correspond to the FHIR resources recorded in the UGR, following the mechanism defined in the CDS Hooks specification.