CurrentColorado Rocky Mountain Health PlansPolicy CS149OH.F

Pharmacogenetic Panel Testing (for Ohio Only)

Governs pharmacogenetic multi-gene panel testing (five or more genes) and related molecular signature tests for members in Ohio; defines coverage stance, references InterQual criteria, and lists applicable procedure codes.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyPharmacogenetic Panel Testing (for Ohio Only)

Policy CodePolicy CS149OH.F

Change TypeDefinition and supporting information updated

Effective DateFeb 1, 2026

Next Review Date

Key ActionEvaluate requests for services and apply Ohio Administrative Code 5160-101 and InterQual CP criteria to determine medical necessity.

SourceLink

POLICY UPDATE CHANGES

Updated definition of 'Multi - Gene Panel' and updated Supporting Information sections (Description of Services, Clinical Evidence, FDA, and References) to reflect the most current information.

Ohio onlyApplies to

5+ genesMinimum genes

2026-02-01Policy revision

20%–49%Response benefit (range)

41%–78%

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Remission benefit (range)

Coverage Criteria and Evidence Summary

inv-01: Not Medically Necessary - Multi-Gene Panels

Covered when referencing clinical criteria sources and stating policy stance.

Not covered when all apply: Pharmacogenetic Multi-Gene Panels (five or more genes) are considered unproven and not medically necessary for any indication due to insufficient evidence of efficacy.five or more genes

Refer to InterQual CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response for medical necessity clinical coverage criteria.

inv-02: Not Medically Necessary - PrismRA

Specific test-level noncoverage statement and rationale.

PrismRA test: Use of the PrismRA molecular signature response classifier (MSRC) is unproven and not medically necessary for evaluating likelihood of inadequate response to anti-TNF therapies for rheumatoid arthritis due to insufficient evidence of efficacy and low overall evidence quality.

Studies report increased alignment of therapy with MSRC results but evidence is limited by nonrandomized design, potential bias, and limited racial diversity; insurance-related deviations from recommendations were reported.

inv-03: Evidence synthesis and applicability

Summary considerations drawn from the evidence base to inform applicability of pharmacogenomic testing.

Psychiatric indications with some supporting evidence: Randomized trials, systematic reviews, and meta-analyses report modest early improvements (commonly at 8–12 weeks) in response and remission for major depressive disorder when PGx-guided therapy includes CYP2C19 and CYP2D6; however, results are heterogeneous, often industry-funded, and not consistently durable at later time points.improvements reported at week 8–12 in multiple meta-analyses

Heterogeneity in panels, proprietary algorithms, trial design limitations, and limited generalizability are important caveats.

Actionable-phenotype subgroup effects: Some trials and subgroup analyses show greater benefit among individuals with actionable genotypes (e.g., CYP2C19/CYP2D6), but these subgroups are often small and may lack power to confirm effect sizes.~25% actionable results in some trial subgroups (PREPARE reporting actionable findings)

Subgroup findings may not generalize and require cautious interpretation.

The PrismRA® molecular signature response classifier (MSRC) is a combined biomarker panel that integrates gene expression features, serologic markers, and clinical metrics to predict the likelihood of nonresponse to anti‑TNF biologic/targeted synthetic DMARD therapy in rheumatoid arthritis. The policy states that use of the PrismRA test is unproven and not medically necessary for evaluating likelihood of inadequate response to anti‑TNF therapies because the published evidence is of very low quality and does not establish clinical efficacy or consistent clinical utility.

A Hayes Molecular Test Assessment (updated through 2025) concluded there is insufficient evidence of analytic and clinical validity to support use of the GeneSight Psychotropic panel in mental health disorders; Hayes rated the test as lacking adequate evidence. Consistent with that assessment, the policy highlights that tests without demonstrated analytic or clinical validity (GeneSight given as an example) are not supported, and providers should expect potential noncoverage when relying on those proprietary panel results alone.

Routine use of multigene PGx panels to predict anthracycline chemotherapy‑induced cardiotoxicity is not supported by current evidence and requires further prospective validation before it can be considered clinically useful. Similarly, although some small trials and cohort studies have reported PGx‑guided improvements in postoperative pain management or reduced opioid consumption in selected high‑risk phenotypes, systematic reviews and Hayes evaluations conclude the overall evidence for routine PGx panel use in pain management and opioid therapy is very limited and insufficient to demonstrate consistent clinical benefit.

The policy identifies common scenarios where multigene PGx panels have been proposed — multimorbidity and polypharmacy, optimizing prescribing around cancer treatment to reduce toxicity, and identifying medication response or adverse reaction risks — but states that evidence is insufficient to support routine use of panels for these broad indications. For patients undergoing percutaneous coronary intervention (PCI), modeling and cohort data suggest panel testing could identify genotype‑guided prescribing opportunities beyond single‑gene (CYP2C19) testing, yet high‑quality outcome data proving patient benefit are lacking; therefore panels are not endorsed for routine use in these contexts.

The American Academy of Child and Adolescent Psychiatry (AACAP) recommends clinicians avoid using pharmacogenetic testing to select psychotropic medications for children and adolescents, noting limitations in existing studies (small samples, short follow‑up, conflicts of interest) and that PGx testing offers little meaningful information when multiple concurrent medications are used.

This policy is informational and must be applied consistent with the member’s governing benefit terms. Plan determinations of coverage are governed by applicable federal, state (Ohio Administrative Code), or contractual benefit requirements; in the event of a conflict those terms control. For clinical coverage decisions regarding pharmacogenomic testing for psychotropic medication response, the policy defers to InterQual® criteria as the primary source for medical necessity determinations.

Pharmacogenetic Multi‑Gene Panels that include five or more genes are explicitly considered unproven and not medically necessary for any indication in this policy due to insufficient evidence demonstrating clinical efficacy or improved patient outcomes.

Real‑world claims analyses and retrospective cohort studies have not demonstrated a clear improvement in clinical outcomes after routine multigene PGx panel testing. One large matched claims analysis observed no benefit and in some comparisons a higher event rate in tested patients, supporting the policy’s conclusion that routine panel testing lacks established real‑world outcome improvement.

Systematic reviews and Clinical Utility Evaluations (Hayes) report very limited evidence that PGx testing improves outcomes for opioid prescribing or predicts opioid dependence. While a small number of studies show benefit in individuals with high‑risk CYP2D6 phenotypes, overall evidence is insufficient to support routine multigene panel–based guidance for opioid therapy.

Clinical Indications and When Testing May Inform Care

inv-50: Use InterQual for psychotropic medication pharmacogenomic testing medical necessity determinations

Operational instruction for psychotropic medication PGx medical necessity determinations.

InterQual referral: Medical necessity determinations for pharmacogenomic testing to guide psychotropic medication selection and dosing should be evaluated using the InterQual CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response.

This policy defers to InterQual criteria for clinical coverage decision-making rather than providing positive coverage criteria within this document.

inv-51: Major depressive disorder and other psychiatric disorders where PGx-guided treatment may inform medication selection

Clinical context where PGx-guided treatment may be informative.

Major depressive disorder (MDD): PGx-guided prescribing has the strongest and most consistent supporting evidence for adults with MDD, showing modest early improvements in response/remission when CYP2C19 and CYP2D6 are included in testing panels.

Applicable Procedure and Billing Codes

Applicable CPT/PLA Codesmixed

0029U	Drug metabolism (adverse drug reactions and drug response), targeted sequence analysis (i.e., CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP4F2, SLCO1B1, VKORC1 and rs12777823).
0173U	Psychiatry (i.e., depression, anxiety), genomic analysis panel, includes variant analysis of 14 genes.
0175U	Psychiatry (e.g., depression, anxiety), genomic analysis panel, variant analysis of 15 genes.
0345U	Psychiatry (e.g., depression, anxiety, attention deficit hyperactivity disorder [ADHD]), genomic analysis panel, variant analysis of 15 genes, including deletion/duplication analysis of CYP2D6.
0347U	Drug metabolism or processing (multiple conditions), whole blood or buccal specimen, DNA analysis, 16 gene report, with variant analysis and reported phenotypes.
0348U	Drug metabolism or processing (multiple conditions), whole blood or buccal specimen, DNA analysis, 25 gene report, with variant analysis and reported phenotypes.
0349U	Drug metabolism or processing (multiple conditions), whole blood or buccal specimen, DNA analysis, 27 gene report, with variant analysis, including reported phenotypes and impacted gene-drug interactions.
0350U	Drug metabolism or processing (multiple conditions), whole blood or buccal specimen, DNA analysis, 27 gene report, with variant analysis and reported phenotypes.
0392U	Drug metabolism (depression, anxiety, attention deficit hyperactivity disorder [ADHD]), gene-drug interactions, variant analysis of 16 genes, including deletion/duplication analysis of CYP2D6.
0411U	Psychiatry (e.g., depression, anxiety, attention deficit hyperactivity disorder [ADHD]), genomic analysis panel, variant analysis of 15 genes, including deletion/duplication analysis of CYP2D6.

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Minimum genes for panel definition

Policy minimum panel size>= 5 genes (policy focuses on panels with five or more genes)

CPT 81418 requirementCPT 81418 specifies a genomic sequence analysis panel must include testing of at least 6 genes (including CYP2C19 and CYP2D6 with CYP2D6 duplication/deletion analysis)

Policy scope notePolicy is designed to address Multi‑Gene Panel testing that laboratories have developed to include five or more genes for proactive evaluation of drug response

Provider Requirements, Prior Authorization, and Documentation

Note

Medical necessity and governing benefit requirements

Application: Medical necessity evaluations for requests described as unproven or subject to coverage/quantity limits will be performed per Ohio Administrative Code 5160-101. Reviewers must reference federal, state (OAC), or contractual benefit terms; in case of conflict, those requirements govern.

Medical necessity evaluation per Ohio Administrative Code (OAC 5160-101).
Governing benefit requirements (federal/state/contractual) take precedence.

Note

Use InterQual for psychotropic PGx criteria

InterQual is the primary source for medical necessity criteria for pharmacogenomic testing related to psychotropic medications. When InterQual lacks applicable criteria, other UnitedHealthcare policies or utilization review guidelines approved by the Ohio Department of Medicaid may be used.

Use InterQual CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response.
Fallback to UHC policies/Guidelines only when InterQual is not applicable.

Member and Test Eligibility Considerations

Eligibility for pharmacogenetic testing should be considered in the context of clinical presentation and prior treatment history; many trials enrolled patients with prior inadequate response to multiple antidepressants, implying testing is often studied in difficult‑to‑treat populations. Targeted single‑gene testing (for example, CYP2C19 around PCI) is generally supported by stronger evidence and may be considered before ordering broader multigene panels.

When evaluating eligibility for testing related to chemotherapy toxicity, the policy highlights targeted germline pharmacogenetic tests — for example, DPYD, NUDT15, TPMT, and UGT1A1 — as tests with clearer associations to treatment‑related risk; these targeted tests differ from broader multigene panels and are the preferred approach where evidence supports use.

Other eligibility considerations and operational approaches include using centralized PGx evaluation units to triage requests and documenting prior medication trials, baseline symptom scores, and how test results would alter management. Ultimately, coverage and eligibility decisions must align with federal, state (OAC), and contractual plan terms.

Services Not Covered

Consistent with the coverage stance, the policy lists as not covered both multigene pharmacogenetic panels of five or more genes and the PrismRA molecular signature test, stating these interventions are unproven and not medically necessary for any indication.

The policy notes that tests lacking demonstrated analytic or clinical validity may be considered unsupported; the Hayes assessment of GeneSight is cited as an example where insufficient evidence was found to support clinical utility and where noncoverage or denial is possible.

Routine multigene PGx panel testing is not covered for prediction of chemotherapy‑induced cardiotoxicity (anthracyclines) and is not covered for routine use in pain management or opioid prescribing because current systematic reviews and evaluations conclude evidence is limited and insufficient to support routine panel‑based interventions in these settings.

The PrismRA evidence base has been assessed as very low quality overall by independent review (Hayes), and the policy states that PrismRA and broader multigene PGx panels lack sufficient high‑quality evidence to support clinical use — a rationale for noncoverage of these tests.

No current CPIC guidelines or other reviewed clinical practice guidelines provide recommendations supporting the routine use of multigene panels that include testing of five or more genes. The absence of guideline recommendations for broad panels is cited as a factor in considering such panels not covered.

Background and Definitions

Pharmacogenetics studies how genetic variation affects medication response. Single‑gene tests (for example, CYP2C19 or CYP2D6) can inform dosing or drug selection for specific medications where evidence and guidelines exist, whereas broader multigene panels (defined in this policy as tests of five or more genes) attempt to provide broader prescribing guidance but currently lack consistent evidence of clinical utility for most indications.

Multi‑Gene Panel (definition & NGS context)

DefinitionMulti‑Gene Panel: genetic tests that typically use next‑generation sequencing to test multiple genes simultaneously; also called multigene test or multiple‑gene panel test (NCI Dictionary, 2025)

Typical technology/contextOften implemented using next‑generation sequencing (NGS) approaches to analyze multiple pharmacogenes simultaneously

Policy focusThis policy addresses Multi‑Gene Panels that include five or more genes to proactively evaluate possible drug responses

Combinatorial pharmacogenetic (PGx) test

Policy Revision History

2026-02-01definition_updateLatest

Updated definition of 'Multi - Gene Panel' and revised Supporting Information (Description of Services, Clinical Evidence, FDA, References); archived prior policy version CS149OH.E.

2026-02-01evidence_summary_updateLatest

Policy updated supporting information and evidence synthesis sections to reflect recent systematic reviews, meta-analyses, RCTs, and cohort/simulation studies addressing PGx testing and PrismRA/MSRC evidence; changes summarize recent findings on psychiatric indications, PCI contexts, and limitations of current multigene panels.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyPharmacogenetic Panel Testing (for Ohio Only)

Policy CodePolicy CS149OH.F

Change TypeDefinition and supporting information updated

Effective DateFeb 1, 2026

Next Review Date

Key ActionEvaluate requests for services and apply Ohio Administrative Code 5160-101 and InterQual CP criteria to determine medical necessity.

SourceLink

On This Page

Cardiovascular/PCI context: Cohort and simulation studies indicate that multigene PGx testing could identify genotype-guided prescribing opportunities in a meaningful fraction of PCI patients, yet direct high-quality randomized outcome data demonstrating improved clinical endpoints are limited.simulated opportunities ~26.5 per 100 PCI patients; projected genotype-guided prescribing 32%–52% over follow-up

Targeted CYP2C19 testing around PCI has the strongest evidence base among cardiovascular applications; panel-based approaches remain investigational for improving outcomes.

Adverse drug reaction reduction trials: Cluster-randomized trials of focused multigene panels (example: PREPARE 12-gene panel) have demonstrated reduced incidence of clinically significant ADRs in trial settings, supporting potential safety benefits, though generalizability across populations and settings is limited.PREPARE showed reduced ADRs (OR 0.70) in trial population

Ancestry differences, setting heterogeneity, and trial conduct may limit applicability to routine U.S. clinical practice.

Chemotherapy toxicity and targeted germline testing: Large genomic cohort analyses indicate clinically relevant actionable variants in genes such as DPYD, NUDT15, TPMT, and UGT1A1 that are associated with chemotherapy toxicity risk, supporting targeted single-gene or small-panel testing in oncology contexts rather than routine broad multigene panel use.high prevalence of actionable variants in focused cancer cohorts (e.g., 62.7% in subset analyses)

Prospective validation and integration with treatment protocols are needed before broad panel deployment for chemotherapy toxicity prediction.

improvement often observed at 8–12 weeks

Trials frequently enrolled individuals with prior inadequate response to medications (difficult-to-treat populations); applicability to first-line treatment is less certain.

Other psychiatric disorders: Evidence for anxiety, bipolar disorder, and psychotic disorders is more limited and heterogeneous; some small trials and systematic reviews report possible benefit but methodological limitations warrant cautious interpretation.small trials with fewer than 300 individuals often nonblinded

ISPG and CPIC support CYP2C19/CYP2D6 testing for antidepressant/antipsychotic dosing, but overall guideline support for broad multigene panels is limited.

inv-52: Individuals undergoing PCI — potential PGx-guided prescribing opportunities

Context for PGx testing surrounding percutaneous coronary intervention (PCI).

PCI patient opportunities: Modeling and cohort analyses suggest multigene PGx testing could identify genotype-guided prescribing opportunities for a substantial proportion of PCI patients, but evidence demonstrating improved clinical outcomes from panel-based testing is limited and further high-quality studies are required.simulated opportunities ~26.5 per 100 PCI patients; projected genotype-guided prescribing 32%–52% over follow-up

Targeted CYP2C19 testing has stronger direct evidence for antiplatelet therapy guidance than broad panels.

inv-53: Genotype-guided antiplatelet therapy around PCI — targeted CYP2C19 testing evidence base

Evidence focus for antiplatelet therapy decisions around PCI.

Genotype-guided antiplatelet therapy: Targeted CYP2C19 testing to guide antiplatelet selection around PCI has the most direct evidence base; panel-based testing at the time of PCI could identify additional prescribing opportunities but lacks definitive high-quality outcome data.

Consider targeted single-gene CYP2C19 testing as the primary evidence-supported approach for antiplatelet decision-making.

inv-54: Use of a 12-gene PGx panel to reduce adverse drug reactions — PREPARE trial context

Trial evidence on use of a focused multigene panel to reduce adverse drug reactions (ADRs).

PREPARE 12-gene panel findings: The PREPARE cluster-randomized trial of a 12-gene PGx panel demonstrated a reduction in clinically significant ADRs in the trial population, supporting potential safety benefits of targeted multigene panels under trial conditions.reduction in ADR incidence (OR 0.70) in trial population

Generalisability may be limited by differences in ancestry, healthcare settings, and trial conduct.

inv-55: Use of PrismRA/MSRC to guide b/tsDMARD selection in rheumatoid arthritis — evidence and limitations

Evidence and limitations regarding use of PrismRA/MSRC to direct b/tsDMARD selection in RA.

PrismRA/MSRC-guided RA therapy evidence: Cohort studies report that PrismRA/MSRC results often align with clinician treatment selection and that MSRC-guided therapy was associated with improved short-term outcomes; however, evidence quality is limited by nonrandomized design, potential conflicts of interest, limited racial diversity, and lack of randomized controlled confirmation.MSRC nonresponse signature seen in ~59% of tested RA cohort; MSRC-aligned treatment provided in ~70%

Insurance-related barriers commonly explained deviations from test recommendations in studies; overall evidence rated very low quality for broad clinical adoption.

inv-56: Targeted germline PGx testing (DPYD, NUDT15, TPMT, UGT1A1) for chemotherapy toxicity risk

Targeted germline PGx testing for chemotherapy toxicity risk.

Oncology-focused targeted PGx testing: Targeted germline testing of DPYD, NUDT15, TPMT, and UGT1A1 identifies variants associated with increased risk of toxicity from specific chemotherapeutic agents and supportive drugs, supporting use of focused testing to inform dosing or alternative therapy choices in oncology patients.high prevalence of actionable variants in focused cancer cohorts (e.g., 62.7% in subset analyses)

Large retrospective genomic analyses support clinical relevance, but prospective validation and integration into care pathways are recommended.

inv-57: Consider PGx testing for pain management toxicity/response concerns per NCCN adult cancer pain guidance

Situations when PGx testing may be considered for pain management.

Pain management with toxicity or inadequate response concerns: Per NCCN adult cancer pain guidance, consider PGx testing before or during pain treatment when concerns exist about toxicity or lack of analgesic response; small trials suggest potential benefit in selected postoperative and analgesic-prescribing contexts.clinical concern for toxicity or treatment failure

Routine use of broad multigene panels for pain management is not supported by sufficient evidence; targeted gene tests (e.g., CYP2D6) are more established for specific drug decisions.

inv-58: Use of CYP2D6 and CYP2C19 genotyping for antidepressant/antipsychotic dosing (CPIC/ISPG supported)

Guideline-supported gene-specific genotyping to inform psychotropic medication prescribing.

CYP2D6 and CYP2C19 genotyping for psychotropics: CPIC and ISPG statements support use of CYP2D6 and CYP2C19 genotyping to inform selection and dosing of many antidepressant and antipsychotic medications; targeted single-gene results should be used to guide therapy when applicable.use per CPIC/ISPG gene-drug recommendations

This supports targeted testing rather than routine broad multigene panels for psychotropic medication management.

Prior Authorization

Prior authorization — plan verification recommended

Prior authorization: the policy text does not specify a statewide prior authorization process. However, for routine multigene pharmacogenomic (PGx) panel testing (panels with ≥5 genes) insurers commonly require prior authorization due to evolving evidence and utilization concerns. Providers should check the member's benefit plan for any plan-specific prior authorization requirements before ordering.

Prior authorization not specified in this policy text — confirm on a plan-by-plan basis.
Prior authorization likely required for routine multigene PGx panels (≥5 genes).

Documentation Required

Centralized PGx unit triage and approval (implementation example)

Centralized triage and approval by a pharmacogenetics unit is an implementation example that may be used to evaluate clinical usefulness of requested PGx tests. In that model (La Paz), ordering providers submit requests and a centralized unit reviews appropriateness by category and approves only tests judged clinically useful.

Triage and approval by centralized PGx unit (La Paz example).
Approval required by centralized PGx unit for tests judged clinically useful; many requests may be declined.

Denial Risk

Denial risk — multigene panels and specific proprietary tests

Not medically necessary: multigene pharmacogenetic panels (five or more genes) are considered unproven and not medically necessary for any indication due to insufficient evidence. Specific proprietary tests such as PrismRA for predicting anti‑TNF nonresponse in rheumatoid arthritis are also considered unproven and not medically necessary.

Not medically necessary: multigene PGx panels (≥5 genes).
Not medically necessary: PrismRA molecular signature test for anti‑TNF response in RA.

Step Therapy

Insurance, prior authorization, and step-therapy impacts

Insurance and step-therapy considerations can affect whether providers follow PGx or MSRC recommendations. Studies and cohort reports note insurance coverage concerns and potential insurer step-therapy requirements; when payers impose step-therapy or coverage limits it may prevent alignment of prescribed therapy with test recommendations.

Insurance/prior authorization considerations are a common barrier to following PGx/MSRC recommendations.
Step-therapy context in trials: many RCTs and cohorts enroll participants after prior inadequate responses or in settings where insurer step-therapy was not accounted for.
Step-therapy impacts: insurer-driven sequences may alter clinical utility and modeling assumptions.

Documentation Required

Provider documentation and claims support

When a PGx or MSRC test is performed, document the test result, the medication chosen, and whether the treatment aligned with the test recommendation (congruent vs incongruent). For claims review and medical necessity adjudication, include supporting documentation such as clinical rationale for testing, prior medication history, prior inadequate responses, and dates of assessments.

Record test result and whether therapy aligned with MSRC/PGx results.
Suggested documentation elements: prior medication trials and failures, assessment timepoints (e.g., weeks 4, 8, 12, 24), clinical outcome measures (PHQ‑9, HAMD‑17, ACR responses).
Supporting documentation for claims review: clinical notes, medication lists, insurer correspondence, prior authorization approvals/denials.

Note

Prefer targeted gene testing over routine multigene panels

Favor targeted single-gene testing when high-quality evidence and actionable guidance exist (for example, CYP2C19 for antiplatelet therapy) before ordering broader multigene panels. Targeted test results may suffice to guide therapy per CPIC guidance and are less likely to be subject to medical necessity denial.

Favor targeted gene testing (e.g., CYP2C19) before broad panels when evidence/guidelines support it.
Use targeted gene results to guide therapy in accordance with CPIC recommendations.

DefinitionCombinatorial PGx test: a proprietary algorithmic panel that combines genotype results from multiple genes into an integrated recommendation (example: proprietary algorithms used in some psychiatry trials)

Clinical use noteProprietary combinatorial tests were used in RCTs (e.g., GUIDED, NeuroIDgenetix) to generate treatment recommendations, but algorithms and included genes vary across products

Interpretation cautionHeterogeneity of panels and proprietary scoring limits comparability and generalizability of results

Actionable phenotype

DefinitionActionable phenotype: a genotype (e.g., CYP2C19 or CYP2D6 metabolizer status) that indicates altered drug metabolism and leads to an actionable prescribing recommendation

Example impactIn PREPARE and other studies, participants with actionable phenotypes had fewer adverse drug reactions or provided opportunities for genotype‑guided prescribing

Prevalence noteActionable phenotypes are common in studied cohorts (e.g., ~25% actionable in PREPARE psychiatric subgroup; 77% had at least one actionable phenotype in a PCI cohort for five genes)

CPIC A/B drugs — definition & relevance

DefinitionCPIC A/B drugs: medications for which the Clinical Pharmacogenetics Implementation Consortium issues level A or B recommendations to guide prescribing based on genotype

RelevanceCPIC A/B drugs are commonly referenced in cohort and simulation studies (e.g., PCI analyses) as targets where genotype information may change therapy

Guideline originCPIC produces evidence‑based, peer‑reviewed, updatable gene/drug clinical practice guidelines to translate genetic results into prescribing decisions

PrismRA / Molecular Signature Response Classifier (MSRC)

DefinitionPrismRA / MSRC: a molecular signature response classifier (PrismRA by Scipher Medicine) combining gene expression features, serologic markers, and clinical metrics to predict likelihood of nonresponse to anti‑TNF therapies in rheumatoid arthritis

ComponentsPrismRA evaluates 23 assessments including 19 gene expression features, anticyclic citrullinated protein, and three clinical metrics (sex, BMI, patient disease assessment)

Evidence noteCurrent evidence for PrismRA is limited; larger independent studies with stronger designs are needed to establish clinical utility

PGx multigene panel example — 12‑gene PREPARE

Example panelPREPARE trial used a 12‑gene PGx multigene panel to guide treatment and reported reduced adverse drug reactions in the trial population

ContextAlthough 12 genes were assayed, PREPARE analyses of psychiatric subgroup focused on CYP2C19 and CYP2D6 for psychiatric drug metabolism

Generalizability notePREPARE showed reduced ADRs overall, but applicability may be limited by population differences and heterogeneity across settings

CPIC — consortium definition and role

DefinitionCPIC: Clinical Pharmacogenetics Implementation Consortium — international consortium producing evidence‑based, peer‑reviewed, updatable gene/drug guidelines to translate genetic results into actionable prescribing decisions

RoleCPIC guidelines summarize the effect of genotypes (e.g., CYP2D6, CYP2C19, CYP2B6) on dosing, efficacy, and tolerability and are cited as implementation resources

EndorsementsCPIC guidelines are indexed in PubMed and endorsed by professional societies (e.g., ASHP), and serve as a key resource for translating genotype to prescribing actions

PharmArray (La Paz implementation example)

PharmArray examplePharmArray: a 180‑SNP pharmacogenetic panel used in the La Paz University Hospital implementation to test multiple PGx markers

Implementation modelLa Paz used a centralized PGx testing unit to triage orders and approved tests based on clinical category (A/B/C), with 600 of 2,539 requests approved

Program outcomesIn the approved subgroup, 32% had a molecular profile that impacted drug therapy and 58% of those had a dose adjustment

Multi‑Gene Panel — updated definition (revisions)

Updated definition documentedPolicy revision (02/01/2026) updated the definition of 'Multi - Gene Panel' to reflect current information (per Policy History)

Policy focusDocumented definition clarifies the policy targets Multi‑Gene Panels (five or more genes) for coverage considerations

Supporting information updatedSupporting sections (Description of Services, Clinical Evidence, FDA, References) were updated alongside the definition in the revision