The content in this section may be significantly revised prior to the next ballot after initial use and feedback.

This section provides guidance for genomic reporting about the implication of a patient's genetics on the behavior of one or more medications. This includes making recommendations for medication adjustments. This portion of the implementation guide relies on the content in the General Genomic Reporting and Variant Reporting portions of this implementation guide. Pharmacogenomic reports supplement this information with a set of pharmacogenomic-specific implication profiles. Implementers of pharmacogenomic reporting may also be interested in the Somatic Reporting section of this implementation guide.

Communicating disease or tumor context

In general, treatments and medications have a set of indications for use which are not explicitly stated. However, if a pharmacogenomics statement has a specific context of a disease or a tumor use the component phenotypic-treatment-context to indicate the disease.

Pharmacogenomic-specific Genomic Implications

Figure 1: Pharmacogenomic Implications

(Profile links: Genomic Implication, Therapeutic Implication, Medication Recommendadtion)

There are two ways to communicate details about a medication whose implication is being described. The profile component medication-assessed is the place to communicate a simple code for the medication. If more detail about the medication is to be shared, use the extension also named medication-assessed. The extension can refer to a Medication or MedicationKnowledge resource. This might be used to share specific classification details if they are important as part of the implication being described. It is important to note that since there two ways to do this, implementers SHALL ensure consistent usage. If both the extension and component are used at the same time, they SHALL deliver the same medication code. Because this is an international profile, no guidance is provided on drug coding systems.

It is important to note there are also two ways to communicate details about non-medication therapies (e.g. altered diet, radiation therapy, surgery, etc.). The profile component therapy-assessed is the place to communicate a simple code for the therapy. If more detail about the therapy is to be shared, use the extension also named therapy-assessed. The extension can refer to a CarePlan, ResearchStudy, or PlanDefinition resource. It is important to note that since there two ways to do this, implementers SHALL ensure consistent usage. If both the extension and component are used at the same time, they SHALL deliver the same therapy code. Because this is an international profile, no guidance is provided on therapy coding systems.

The component predicted-therapeutic-implication lists one or more ramifications based on the presence of associated molecular finding(s), which may include:

• Alterations in drug metabolism (or pharmacokinetics) that determine the concentration of the drug, prodrug, and/or break-down products over time;
• Alterations in drug efficacy (or pharmacodynamics) that determine how effective a drug is at a given concentration;
• Alterations that alter the risk of adverse drug events, or other types of implications that indicate altered responsiveness to other types of therapies or eligibility for clinical trials;
• Other pharmacogenomic statements as necessary, by extending the valueSet.

Including Pharmacogenomic recommended actions

To associate a therapeutic implication instance with a recommendation (e.g. discontinuing a medication, altering dosage, choose alternative medication) use Medication Recommendation, Followup Recommendation, along with current medication if appropriate. Use related-artifact for supporting documents such as CPIC guidelines.

Medication Recommendation tasks link to therapeutic implications through reasonReference and are included in the report using the recommended-action extension. The therapeutic implications do not have a link to medication recommendations, so the revinclude search parameter can be used to find the therapeutic implication statements relevant to the recommendations.

Note: If multiple medications are used in medication assessed, the usage implication should describe the combined effect.

Note 2: Implementers may also be interested in the Somatic Reporting and Pharmacogenomics Reporting sections of this implementation guide.

Differentiating AND vs OR

There are several cases where it is necessary to differentiate 'AND' conditions (e.g. both drug X AND drug Y, in combination, are indicated in the presence of a variant) vs. 'OR' conditions (e.g. either drug X OR drug Y are indicated in the presence of a variant). This situation is not unique to genomic implications, and arises elsewhere within FHIR (e.g. FHIR Search) and outside of FHIR (e.g. Clinvar submission API condition set). To be consistent with other precedents:

Where diagnostic and therapeutic implications have fields with cardinality >1, the inclusion of multiple values within a field shall indicate an 'AND' condition. An 'OR' condition is represented by multiple observation instances.

See Genomic Implication for additional information.

Implication fields affected by this guidance include:

derivedFrom, evidence-level, phenotypic-treatment-context, medication-assessed, therapy-assessed, predicted-therapeutic-implication.