ModifiedUnitedHealthcarePolicy CS149NM.F

Pharmacogenetic Panel Testing (for New Mexico Only)

This UnitedHealthcare medical policy governs coverage of pharmacogenetic multi-gene panel testing (five or more genes) and related molecular signature tests for members in New Mexico.

Policy Summary

PayerUnitedHealthcare

PolicyPharmacogenetic Panel Testing (for New Mexico Only)

Policy CodePolicy CS149NM.F

Change TypeDefinition updatedsupporting information refreshed

Effective Date01/01/2026

Next Review DateN/A

Key ActionCheck federal, state, and contractual benefit requirements and obtain prior authorization when required before ordering multigene PGx panels.

SourceLink

POLICY UPDATE CHANGES

Updated definition of 'Multi - Gene Panel'.

Updated Description of Services, Clinical Evidence, FDA, and References sections to reflect the most current information.

PrismRANamed test not medically necessary

>=5 genesDefinition threshold

21% vs 27.7%ADR reduction (PREPARE)

62.7%Clinically relevant variants

CS149NM.E

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Prior version archived

Coverage Criteria

Not Medically Necessary — Multi-Gene Panels

Coverage stance for pharmacogenetic multi-gene panels and related molecular signature tests

Not medically necessary — multi-gene panels: The use of pharmacogenetic Multi-Gene Panels (five or more genes) for the evaluation of drug-metabolizer status is unproven and not medically necessary for any indication due to insufficient evidence of efficacy.

Supported by Coverage Rationale.

Not Medically Necessary — PrismRA

Not medically necessary — PrismRA: The use of the PrismRA ® molecular signature test 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.

Supported by Coverage Rationale and Hayes assessment.

Indication-specific coverage rationale

Coverage stance varies by indication; evidence summarized below informs limits.

Cardiovascular: PGx panel testing including CYP2C19, CYP2C9, VKORC1, F5, F2, and MTHFR showed no real-world improvement in outcomes in a large retrospective claims cohort and therefore should not be considered generally clinically necessary for improving cardiovascular outcomes based on current evidence.

Billings et al. retrospective claims analysis indicated no improved outcomes and potential increased adverse events.

Anthracyclines (chemotherapy-induced cardiotoxicity): Routine use of PGx panel testing to assess risk of anthracycline-induced cardiotoxicity is not supported for routine clinical use; although multiple variants and predictive models were identified, the certainty of evidence is very low and further prospective, ethnically diverse validation and standardized panels are required before routine coverage.

Systematic review/meta-analysis identified candidate variants but concluded evidence certainty was very low and panels are not standardized.

Pain management: Multigene PGx panel testing for predicting opioid response, dependence, or improving pain outcomes has mixed evidence: some small RCTs and observational studies report benefits in select surgical and perioperative settings, but overall evidence is limited and heterogeneous; routine broad panel testing for pain management is not established as medically necessary.

Randomized trials (e.g., Kraus et al., Hamilton et al.) show mixed results; policy concludes insufficient evidence for general use.

The policy considers pharmacogenetic multi-gene panels (five or more genes) for evaluation of drug-metabolizer status to be not medically necessary for any indication due to insufficient evidence of efficacy. This exclusion applies broadly to panels meeting the policy definition of five or more genes and is supported by the Coverage Rationale that such use is unproven and lacks demonstrated clinical benefit.

Routine use of pharmacogenetic panel testing to assess risk of anthracycline-induced cardiotoxicity (chemotherapy-induced cardiotoxicity) is not supported by current evidence. Although systematic reviews and individual studies have identified candidate variants and predictive models with modest discriminatory performance, the certainty of evidence is very low and further prospective, ethnically diverse validation with long-term follow-up is required before routine clinical use can be recommended.

Routine multigene pharmacogenetic panel testing submitted for general pain management—intended to predict opioid response, side effects, dependence, or broadly improve pain outcomes—is not supported as safe or efficacious by the current peer-reviewed literature and is therefore excluded from routine coverage when used for non–indication-specific predictions.

The evidence is currently insufficient to support use of pharmacogenetic multigene panel testing to guide individualized therapies across broad indications such as multimorbidity, polypharmacy, cancer treatment toxicity, inflammatory bowel disease, or generalized prescribing. Published reviews and systematic evaluations report heterogeneity, limited high-quality trials, and a lack of robust clinical efficacy data to justify routine panel-based guidance for these diverse clinical scenarios.

The American Academy of Child and Adolescent Psychiatry (AACAP) advises clinicians to avoid the use of pharmacogenetic testing to select psychotropic medications in children and adolescents, citing limitations in available studies, potential conflicts of interest, small sample sizes, and insufficient evidence when multiple medications are used concurrently.

The PrismRA® molecular signature test (MSRC) for predicting inadequate response to anti‑TNF therapies in rheumatoid arthritis is considered not medically necessary. The policy states that PrismRA is unproven for routine clinical use; independent assessments (Hayes) and the published literature identify a very‑low–quality body of evidence and call for larger, independent studies before PrismRA can be considered to have established clinical utility.

Use of multigene pharmacogenetic testing for cardiac disease lacks high‑quality studies demonstrating improved clinical outcomes. A large retrospective claims analysis found no improvement in real‑world outcomes and, in fact, observed higher rates of certain adverse events in the tested cohort, indicating that routine panel use for cardiovascular outcome improvement is not supported by current evidence.

Pharmacogenetic (PGx) panel testing is not medically necessary when used routinely to improve cardiovascular outcomes, for broad pain‑management prediction without indication‑specific supporting evidence, or to replace established rheumatoid arthritis treatment decision pathways (for example, substituting PrismRA results for established stepwise DMARD/biologic selection) given the limited and inconsistent evidence of clinical utility.

Assessments of the PrismRA test note substantial limitations in the evidence base, including changes in test versioning, small and potentially biased studies, and methodological constraints. A Hayes Molecular Test Assessment rated the body of evidence as very low quality and concluded that additional larger, independent studies are needed before PrismRA can be considered to have proven clinical utility.

Covered Indications and Contexts

General pharmacogenetic testing for drug response or adverse effects

Covered when ALL of the following are met:

General pharmacogenetic testing for drug response or adverse effects: Policy addresses pharmacogenetic testing generally but deems multi-gene panels (five or more genes) unproven and not medically necessary.>=5 genes

Multi-Gene Panels are defined in this policy as tests including five or more genes; targeted single-gene or small multi-gene (eg, warfarin 2-3 genes) testing are conceptually distinct and considered separately in clinical guidance.

Select psychiatric conditions where PGx-guided therapy may be used

Contexts where PGx-guided psychiatric prescribing has been studied; evidence is mixed and often focuses on two key pharmacogenes.

Select psychiatric conditions: PGx-guided therapy may be considered for select psychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, anxiety) to reduce adverse drug reactions or to improve early response/remission, primarily when testing includes CYP2C19 and CYP2D6 and is applied in patients starting or switching therapy or with prior inadequate response.

Not Covered Services

Not covered under this policy are pharmacogenetic multi‑gene panels (five or more genes) for evaluation of drug‑metabolizer status and the PrismRA® molecular signature test for RA anti‑TNF response. Routine panel testing for anthracycline cardiotoxicity, broad pain‑management applications, cardiovascular outcome improvement, and other generalized indications is also not covered due to insufficient, low‑certainty, or inconsistent evidence.

Routine PGx panel testing for predicting chemotherapy‑induced cardiotoxicity is not covered. Systematic reviews and pediatric studies identify candidate variants and some predictive models, but overall certainty is very low and there is a need for prospective, ethnically diverse validation before clinical coverage can be considered.

Routine broad multigene pharmacogenetic panel testing submitted for general pain‑management prediction, cardiovascular outcome improvement, or to guide first‑line biologic selection in rheumatoid arthritis (in lieu of standard treatment algorithms) is not covered because high‑quality evidence demonstrating improved outcomes is lacking.

Use of PGx multigene panel testing for broad clinical indications—such as multimorbidity, polypharmacy, and general prescribing decisions—remains not covered because current literature does not substantiate clinical efficacy or system‑level benefit in these settings.

No existing Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provide recommendations for the routine use of multigene panels that include five or more genes. Guideline variability and the lack of panel‑specific recommendations contribute to the policy decision not to cover broad multigene PGx panels.

Coding

Applicable PLA/RA codes (selection)mixed

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 )

Applicable CPT/PLA/MP codesmixed

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 , reported as impact of gene-drug interaction for each drug.
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.
0419U	Neuropsychiatry (e.g., depression, anxiety), genomic sequence analysis panel, variant analysis of 13 genes, saliva or buccal swab, report of each gene phenotype.

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Minimum gene count for covered panels (policy context)

Policy multi-gene panel thresholdPolicy defines Multi-Gene Panels as tests that include five or more genes (panels of five or more genes).

CPT 81418 minimum gene countCPT 81418 requires genomic sequence analysis panel to include testing of at least 6 genes, including CYP2C19 and CYP2D6 with CYP2D6 duplication/deletion analysis.

Policy scope noteThis medical policy is designed to address Multi-Gene Panel testing, which laboratories have developed to include five or more genes to evaluate responses to many drugs.

Provider Actions and Operational Notes

Billing Rule

Applicable codes — reference

The following list of applicable procedure codes is provided for reference only. Inclusion of a code does not imply coverage, reimbursement, or guarantee of payment. Providers should reference federal, state, and contractual benefit terms and any other applicable rules before billing or requesting authorization.

Applicable codes listed for reference — inclusion does not imply coverage or payment.
Providers must follow contractual, federal, and state requirements when submitting claims.

Prior Authorization

Coverage/authorization can limit use of PrismRA results

Use of PrismRA (MSRC) results to guide treatment may be limited by payer coverage and authorization decisions. When coverage or prior authorization is denied or restricted, clinicians may be unable to align prescribing with PrismRA recommendations.

Definitions

Multi-Gene Panel definition

DefinitionGenetic tests that typically use next-generation sequencing to test multiple genes simultaneously; also called multigene test, multiple-gene panel test, and multiple-gene test.

Typical platformsOften performed using next-generation sequencing (NGS) platforms and may report metabolizer status or variant-level results depending on panel design.

Policy emphasisPolicy focuses on Multi-Gene Panel testing that includes five or more genes and addresses clinical utility and coverage considerations for such panels.

Actionable phenotype

DefinitionA genotype-based metabolic phenotype (e.g., for CYP2C19 or CYP2D6) for which treatment recommendations or alternative dosing/medication choices exist and were used to guide therapy in trials.

Clinical relevance

Eligibility Requirements

No top‑level eligibility requirement nodes are defined in this policy.

Background

Pharmacogenetics evaluates how genetic variation affects medication response and adverse effects. Targeted testing typically analyzes a single gene (or a few genes for specific drug contexts), whereas multi‑gene panels test multiple genes simultaneously—often five or more—and aim to inform drug selection or dosing across multiple medications. This policy focuses on evidence and coverage for multigene PGx panels and related molecular signature tests.

Provider Coding & Billing Notes

Note

Billing Rule

Coding reference: code inclusion is informational only

The policy provides an applicable codes list for reference; inclusion of a code does not imply coverage or guarantee payment — verify coverage and billing with the member's plan.

Listing of a code in this policy does not imply the service is covered or not covered; benefit coverage is determined by federal, state, or contractual requirements.
Providers should reference plan benefit documents and payer instructions for billing and prior authorization.

Policy Revision History

2026-01-01policy_revisionLatest

Updated definition of 'Multi - Gene Panel' and refreshed supporting sections (Description of Services, Clinical Evidence, FDA, and References); previous policy version CS149NM.E archived.

This revision includes updates to references and supporting information; new and updated references are listed in the policy revision segment. Review the References and Policy History sections for details on updated citations and the effective date of this revision.

Policy Summary

PayerUnitedHealthcare

PolicyPharmacogenetic Panel Testing (for New Mexico Only)

Policy CodePolicy CS149NM.F

Change TypeDefinition updatedsupporting information refreshed

Effective Date01/01/2026

Next Review DateN/A

Key ActionCheck federal, state, and contractual benefit requirements and obtain prior authorization when required before ordering multigene PGx panels.

SourceLink

On This Page

Rheumatoid arthritis (PrismRA): PrismRA (MSRC) has limited and low-quality supporting evidence; available studies do not establish sufficient clinical utility to guide first-line biologic/targeted DMARD selection and additional larger independent studies are needed before routine coverage can be recommended.

Policy cites limited body of evidence and Hayes assessment of very low quality.

RCTs and meta-analyses report modest early benefits and reduced ADRs but heterogeneous methods and risk of bias limit conclusions; targeted testing is emphasized.

Assessment of risk for anthracycline-induced cardiotoxicity in pediatric and AYA cancer patients as a research/experimental approach

Anthracycline cardiotoxicity risk assessment: Assessment of risk for anthracycline-induced cardiotoxicity using PGx panels is investigational: studies identified candidate risk and protective variants and combined clinical-genetic models show improved discrimination versus clinical data alone, but evidence certainty is very low and panels lack standardization; routine clinical use is not supported pending prospective validation.

Supported by 2025 systematic review and pediatric studies showing low certainty and need for diverse prospective validation.

PGx-guided perioperative or postoperative pain management in selected surgical populations in research or pilot settings

Perioperative/postoperative pain management (research settings): PGx-guided perioperative or postoperative pain management has been evaluated in small randomized trials with mixed results; while some studies report reduced opioid consumption or improved pain scores in tailored groups, evidence is insufficient to support routine coverage outside research or pilot programs.

Examples include small RCTs in TKA and total joint replacement with conflicting outcomes.

PGx panel-guided prescribing to reduce adverse drug reactions in patients receiving medications with known gene-drug interactions (evidence: PREPARE trial)

Panel-guided ADR reduction (PREPARE and similar): PGx panel-guided prescribing may reduce adverse drug reactions in populations receiving medications with known gene-drug interactions; implementation studies (eg, PREPARE 12-gene panel) and meta-analyses report reduced ADR incidence in some settings, supporting targeted application when gene–drug evidence exists.

Evidence varies by population and drug; benefits observed primarily for ADR reduction rather than definitive efficacy gains.

Consider PGx testing to inform selection or dosing when specific gene–drug evidence exists (e.g., CYP2D6/CYP2C19; HLA alleles; CPIC pairs)

Targeted gene testing when specific evidence exists: Consider PGx testing to inform selection or dosing when specific gene–drug evidence exists (for example, CYP2D6 and CYP2C19 for antidepressants; HLA-A and HLA-B for carbamazepine/oxcarbazepine) and when authoritative guidance (eg, CPIC, ISPG, NCCN) supports interpretation and clinical action.

Professional organizations recommend targeted testing for actionable gene–drug pairs rather than broad combinatorial panels.

PGx-guided prescribing may be useful to reduce hospitalizations and increase medication changes per meta-analysis evidence

Impact on hospitalizations and medication changes: Meta-analysis evidence suggests PGx-guided prescribing may increase medication changes and reduce all-cause hospitalizations in some studies, indicating potential system-level benefits though gaps remain for broader implementation and long-term outcomes.

David et al. 2021 meta-analysis found increased medication changes and reduced hospitalizations in PGx arms.

Various clinical contexts where pharmacogenomic guidance has been studied

Clinical contexts studied: Pharmacogenomic guidance has been studied across various clinical contexts including major depressive disorder, schizophrenia, cancer pharmacogenomics, pain management, rheumatoid arthritis, and cardiovascular interventions; evidence quality and applicability vary by indication and test type.

Supported by randomized trials, systematic reviews, and implementation studies cited in references.

Document any payer denials or coverage restrictions when reporting treatment decisions influenced by PrismRA results.
Consider alternative evidence-based treatment pathways when PrismRA-directed therapies are not covered.

Prior Authorization

Centralized review / clinical appropriateness may be required

Institutions may require centralized review of PGx test requests to determine clinical appropriateness before testing is performed. Centralized review programs can triage tests into categories based on intended use and evidence of clinical utility.

Ordering providers may need to submit a recommendation and request to a centralized testing unit for review.
Tests may be categorized (e.g., preemptive actionable markers; drugs with well-defined protocols; drugs without well-defined protocols) to guide approval decisions.

Documentation Required

Check benefit requirements before authorization

Before submitting a request for PGx testing or prior authorization, check the member's plan benefit terms and any applicable federal or state mandates. In the event of conflict, federal, state, or contractual requirements govern.

Confirm whether the member's plan requires prior authorization for multigene PGx panels or PrismRA testing.
Document alignment with benefit terms when submitting clinical rationale and prior authorization requests.

Denial Risk

Denial risk for multi-gene panels

Pharmacogenetic multi-gene panels that include five or more genes are considered unproven and not medically necessary for evaluation of drug-metabolizer status in this policy and therefore carry a high risk of denial.

Multi-gene panels (≥5 genes) for routine drug-metabolizer evaluation are likely to be denied.
Provide strong clinical justification and reference to plan-specific exceptions if seeking authorization for a multi-gene panel.

Denial Risk

Denial risk for PrismRA

The PrismRA molecular signature test is considered unproven and not medically necessary for evaluating likelihood of inadequate response to anti-TNF therapies for rheumatoid arthritis under this policy and therefore may be denied.

Authorization requests for PrismRA should include robust supporting evidence; expect denials consistent with policy language.
If approved by contract or state/federal mandate, document the basis for exception when submitting claims.

Note

Risk signal from claims-based outcomes

Claims-based analyses have raised safety and outcomes concerns in real-world settings; one large retrospective claims study showed higher incidence of stroke, pulmonary embolism, and deep vein thrombosis among PGx-tested patients versus matched controls.

Be aware that real-world claims analyses have not uniformly demonstrated improved outcomes and may show safety signals.
Document clinical rationale and anticipated benefit when seeking authorization to help address concerns raised by claims-data signals.

Denial Risk

Cardiovascular PGx denial risk

Evidence for cardiovascular PGx panel testing is limited and real-world analyses have not demonstrated clear outcome benefits; this lack of demonstrated clinical utility may result in denial of multigene cardiovascular PGx panels.

Prior authorization for cardiovascular PGx panels is often required; expect scrutiny or denial in absence of strong clinical evidence.
Consider targeted testing (e.g., CYP2C19 for antiplatelet therapy) rather than broad panels when clinically appropriate and supported by guidelines.

Note

Insurance coverage may prevent test-directed prescribing

Concerns about insurance coverage were a common reason clinicians reported for not aligning treatment with MSRC/PrismRA test recommendations; lack of coverage can prevent test-directed prescribing.

When MSRC/PrismRA is not covered, document alternative treatment chosen and the insurance rationale provided.
Discuss potential coverage barriers with patients when ordering tests that may not be covered.

Documentation Required

Documentation of genotype reports and prescribing alignment

Document genotype/phenotype reports and clearly record whether prescribing aligned with PGx recommendations. Include the specific genes/variants tested, test date, laboratory, and how results informed therapeutic decisions.

Include in the medical record: test report, date, laboratory, genes/variants tested, interpretation (phenotype), and clinician rationale for adherence or nonadherence to recommendations.
If not aligned with recommendations, document reason (e.g., insurance denial, step therapy, clinical contraindication).

Documentation Required

Example: centralized test request and approval documentation

Provide example documentation used in centralized review programs: ordering provider recommendation, clinical indication, category assigned by the testing unit (A/B/C), review outcome, and rationale for approval or denial.

Example fields: patient demographics, therapeutic question, requested marker/panel, category (A/B/C), testing unit assessment, approval decision, and any recommended dosing or monitoring changes.
Retain centralized unit correspondence in the chart to support medical necessity determinations.

Documentation Required

Program-based documentation of clinical appropriateness

Programs that implemented centralized review documented clinical appropriateness by categorizing test requests and retaining approval logs and outcome measures. Implementing similar documentation practices supports defensible coverage requests and quality monitoring.

Maintain a record of test approval rates, categories of tests requested, and clinical impact (e.g., percent with dose adjustment).
Use program-based documentation to demonstrate clinical utility when seeking payer exceptions.

Documentation Required

Reference governing benefit terms

When deciding coverage or submitting authorization requests, reference the member's federal, state, and contractual benefit terms. In the event of conflict between this policy and plan-specific terms, the plan terms govern.

Cite plan-specific language and any applicable mandates when requesting exceptions to standard policy positions.
Document the alignment of the requested service with benefit terms in the authorization submission.

Note

Typical clinical context for PGx testing

Typical clinical contexts for PGx testing include patients initiating or switching antidepressant therapy and those with prior inadequate response or adverse reaction to medications. Many trials enrolled patients with previous inadequate response to therapy rather than treatment-naïve populations.

Consider PGx testing primarily for individuals with prior inadequate response or intolerance to standard therapies where gene-drug pairs are actionable.
Avoid routine preemptive broad-panel testing in unselected populations unless supported by clinical need and benefit coverage.

Step Therapy

RA step therapy note

For rheumatoid arthritis, established treatment algorithms typically recommend anti-TNF agents as first-line biologics for many patients. PrismRA seeks to predict nonresponse to anti-TNF therapy, but insurers may require step-therapy adherence before covering alternative biologics.

Document prior DMARD use and failure per insurer step-therapy requirements when requesting authorization for non–TNF-targeted therapies.
If seeking coverage based on PrismRA results, include prior therapy history and specific clinical rationale.

Step Therapy

Insurer step-therapy may restrict implementation

Insurer-imposed step-therapy requirements may restrict implementation of test-guided prescribing even when test results suggest an alternative therapy. Authorization requests should address any required prior therapies and provide documentation of step-therapy failures when applicable.

When step therapy is required, include documentation of prior medication trials, durations, and outcomes in the authorization packet.
Request exceptions only when clearly supported by clinical evidence and plan terms.

Note

Prefer targeted gene testing over broad panel use

Professional guidance and evidence summaries generally favor targeted gene testing for specific actionable gene–drug pairs over broad combinatorial panels for routine care. Targeted testing reduces unnecessary findings and aligns more closely with guideline-supported actions.

Prefer single-gene or small targeted panels (e.g., CYP2C19 for clopidogrel, CYP2D6/CYP2C19 for certain antidepressants) when clinically indicated and supported by guidelines.
Reserve broad multigene panels for situations with clear, documented potential clinical benefit and plan approval.

Actionable phenotypes were used in psychiatric PGx studies (e.g., PREPARE) where CYP2C19/CYP2D6 phenotypes were linked to reduced adverse drug reactions and hospitalizations in a subset with actionable genotypes.

Implication for testingPresence of an actionable phenotype may prompt medication selection or dosing changes consistent with guideline-based recommendations (when evidence supports such actions).

Anthracycline-induced cardiotoxicity (ACT)

DefinitionCardiac dysfunction (including reduced ejection fraction or heart failure) that can occur during or years after treatment with anthracycline chemotherapy.

Genetic associationsMultiple variants (e.g., ABCC2 rs8187710, ETFB rs79338777, GPR35 rs12468485, HNMT rs17583889, UGT1A6 rs17863783) and others have been associated with ACT in systematic reviews and cohort studies.

Evidence certaintyAlthough PGx models combining genetic and clinical data improved predictive accuracy (AUC 0.67–0.87), certainty is very low and further diverse prospective validation is required before routine clinical use.

PGx-guided prescribing

DefinitionUsing pharmacogenetic test results (e.g., CYP2D6 phenotypes, OPRM1 genotypes) to select or dose medications with the intent to improve efficacy or reduce adverse events.

Clinical pathwayPGx-guided prescribing may involve pharmacist or clinician review of genotype results and application of CPIC or other guideline-based dosing or selection recommendations.

Evidence contextRandomized trials and meta-analyses show mixed results across indications; targeted gene–drug pairs (e.g., CYP2C19/CYP2D6 for antidepressants) have stronger support than broad panels.

PrismRA / MSRC

DescriptionPrismRA (MSRC) is a molecular signature response classifier combining gene expression features, serologic markers (anti-CCP), and clinical metrics (sex, BMI, patient disease assessment) to predict likelihood of inadequate response to anti-TNF therapies in RA.

Panel compositionPrismRA evaluates 23 assessments including 19 gene expression features plus anticyclic citrullinated protein and three clinical metrics.

Evidence stanceCurrent evidence is limited; additional larger independent studies are needed before PrismRA can be considered to have proven clinical utility for guiding biologic selection.

Pharmacogenetic (PGx) multigene panel

DefinitionA laboratory test that assesses multiple genetic variants across genes involved in drug response, often including five or more genes; panel composition and analytic platforms vary by vendor.

Typical useIntended to inform medication selection or dosing across multiple therapeutic areas by reporting metabolizer status or gene-drug interactions.

Panel variabilityPanel sizes in cited studies range widely (e.g., 12-gene PREPARE panel to implementations using 180 SNP arrays), and panels frequently include CYP family genes and other pharmacogenes.

Multi - Gene Panel (policy update)

Definition updatePolicy language indicates the definition of 'Multi - Gene Panel' was updated in the 01/01/2026 revision; exact revised wording is provided in the Policy History/Revision Information.

Revision noteSupporting sections (Description of Services, Clinical Evidence, FDA, References) were updated alongside the definition change and previous version CS149NM.E was archived.

Effective dateUpdated definition and supporting information effective 01/01/2026.

Pharmacogenetic testing

DefinitionMultigene pharmacogenetic testing performed to guide medication selection, dosing, or predict adverse events across several genes and drug classes; often used in research, implementation, or targeted clinical contexts.

Clinical examplesPGx multigene testing has been studied in psychiatry (antidepressants, antipsychotics), pain management (opioids, NSAIDs), perioperative settings, and oncology supportive care.

Panel composition noteStudies referenced used panels from 8 to 40+ genes (examples include 12-gene PREPARE panel and 16–25 gene panels in pain and perioperative trials).