CurrentUnitedHealthcarePolicy CS149KS.02

Pharmacogenetic Panel Testing (for Kansas Only)

UnitedHealthcare medical policy (Kansas only) addressing coverage, definitions, evidence review, and applicable CPT/HCPCS codes for pharmacogenetic testing, with focus on multi-gene panels (>=5 genes) and specific proprietary tests. Includes state-specific referral to Kansas Medical Assistance Program and references to InterQual criteria.

Policy Summary

PayerUnitedHealthcare

PolicyPharmacogenetic Panel Testing (for Kansas Only)

Policy CodePolicy CS149KS.02

Change TypeClarified / Added / Removed

Effective DateMarch 1, 2026

Next Review Date

Key ActionFor Kansas members, providers must refer to the Kansas Medical Assistance Program Professional Fee-for-Service Provider Manual for medical necessity criteria and use InterQual® CP for non-state-specific pharmacogenetic testing determinations.

POLICY UPDATE CHANGES

Policy explicitly states it applies only to the state of Kansas and points to Kansas Medical Assistance Program for state-specific criteria.

Added instruction to refer to the InterQual® CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response for medical necessity clinical coverage criteria for pharmacogenetic testing.

Archived previous policy version CS149KS.01.

>=5Multi-Gene Panel gene count threshold (considered unproven)

14-40Range of genes in listed panels (examples)

State applicability (Kansas only)

mixedEvidence supportive status across indications

multipleIndications discussed (cardiovascular, anthracyclines, pain, RA, other)

Coverage Summary

This UnitedHealthcare medical policy applies only to the state of Kansas and addresses pharmacogenetic testing with emphasis on Multi-Gene Panel testing (pharmacogenetic panels). The policy states a policy-level negative coverage stance: the use of pharmacogenetic Multi-Gene Panels (five or more genes) for evaluation of drug-metabolizer status is unproven and not medically necessary for any indication due to insufficient evidence of efficacy. The policy also identifies the proprietary PrismRA® (MSRC) molecular signature test as unproven and not medically necessary for predicting inadequate response to anti-TNF therapies in rheumatoid arthritis. For state-specific medical necessity criteria providers are directed to the Kansas Medical Assistance Program Professional Fee-for-Service Provider Manual, and for non-state-specific pharmacogenetic medical necessity determinations the policy references InterQual® CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response. Key numeric thresholds: a Multi-Gene Panel is defined as testing of five or more genes (considered unproven), and CPT panel code 81418 requires testing of at least 6 genes including CYP2C19 and CYP2D6 with CYP2D6 duplication/deletion analysis.

Policy statistics and thresholds

Multi-Gene Panel gene count threshold>=5

Range of genes in listed panels14-40

State applicabilityKansas only

Evidence supportive statusmixed

Medical Necessity & Coverage Criteria

Coverage / Medical Necessity Statements

Policy-level coverage statements found in this part:

State applicability: This Medical Policy only applies to the state of Kansas.
State-specific coverage reference: For medical necessity clinical coverage criteria for gene analysis (genetic testing), refer to the Kansas Medical Assistance Program, Professional Fee-for-Service Provider Manual.
Non state-specific coverage reference (psychotropic PGx): For medical necessity clinical coverage criteria for pharmacogenetic testing, refer to the InterQual® CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response.
Policy History addition 03/01/2026

Coding

Listed Applicable Proprietary/Panel HCPCS (PLA) / CPT Codes referencedHCPCS|CPT

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, ADHD], genomic analysis panel, variant analysis of 15 genes, including deletion/duplication analysis of CYP2D6.
0347U	Drug metabolism or processing, whole blood or buccal specimen, DNA analysis, 16 gene report, with variant analysis and reported phenotypes.
0348U	Drug metabolism or processing, whole blood or buccal specimen, DNA analysis, 25 gene report, with variant analysis and reported phenotypes.
0349U	Drug metabolism or processing, 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, whole blood or buccal specimen, DNA analysis, 27 gene report, with variant analysis and reported phenotypes.
0392U	Drug metabolism [depression, anxiety, ADHD], gene-drug interactions, variant analysis of 16 genes, including deletion/duplication analysis of CYP2D6.
0411U	Psychiatry [e.g., depression, anxiety, ADHD], genomic analysis panel, variant analysis of 15 genes, including deletion/duplication analysis of CYP2D6.

1–10 of 22

1/3

No procedure/drug CPT/HCPCS/ICD codes provided in this partmixed

No codes listed

Referenced external criteria (InterQual)mixed

No codes listed

Provider Actions & Requirements

Documentation Required

State-specific coverage reference

Kansas providers must refer to the Kansas Medical Assistance Program Professional Fee-for-Service Provider Manual for medical necessity clinical coverage criteria for gene analysis (genetic testing).

Documentation Required

InterQual criteria reference

Refer to InterQual® CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response for non-state-specific medical necessity clinical coverage criteria for pharmacogenetic testing.

Background, Evidence Summary & Definitions

Pharmacogenetics (also called pharmacogenomics) evaluates how genetic variation affects individual medication response, including efficacy and adverse effects. When testing targets a specific drug, single-gene tests (or a small number of genes, e.g., 2–3 for warfarin) are commonly used; laboratories have developed multigene panels to assess responses across many drugs. This policy focuses on evidence for multi-gene panel testing (panels of five or more genes) and reviews the clinical data across psychiatric and cardiovascular indications (among others) to determine whether multi-gene panel testing demonstrates sufficient clinical utility.

Study/Source	Key finding
PREPARE trial (Swen et al., 2023)	12‑gene open-label cluster RCT showed reduced overall adverse drug reactions with PGx‑guided treatment (21.5% vs 28.6%; OR 0.70, p=0.0075); limited generalizability (97.7% European ancestry)
Lingaratnam et al. (2024) meta‑analysis	PGx‑guided cancer/supportive care treatments associated with lower absolute severe adverse events (16% vs 34%; RR 0.72, p=0.006)
PREPARE psychiatry subgroup reports (Skokou et al., 2024)	Among psychiatric participants genotyped with 12‑gene panel, actionable CYP2C19/CYP2D6 phenotypes showed fewer ADRs (≈34% fewer) and fewer hospitalizations in PGx‑guided arm versus control; analysis limited to CYP2C19/CYP2D6
Ratner et al. (2022) - PCI cohort simulation	In 215 PCI patients, 66.5% had ≥1 prescription with actionable PGx recommendations; simulation projected 26.5 genotype‑guided prescribing opportunities per 100 PCI patients
Rouby et al. (2020) - PCI cohort and MarketScan simulation	UF PCI cohort: 77% had ≥1 actionable phenotype (5 genes); projected genotype‑guided prescribing opportunities of 39% at 1 year and 52% at 5 years in MarketScan simulation
Billings et al. (2018) - real‑world cardiovascular claims	Retrospective matched cohort (11,060 tested vs 178,096 controls) found no improved outcomes; tested group more likely to experience stroke/PE/DVT/composite event
David et al. (2021) - systematic review/meta‑analysis	Meta‑analysis found PGx testing led to medication changes more often (4/5 studies) and reduced all‑cause hospitalization in PGx arm, but evidence heterogeneous
Guided/GUIDED/PRIME Care and other psychiatric RCTs (e.g., Oslin et al. 2022, Greden et al. 2019)	Several RCTs show modest early improvements in response/remission and increased medication congruence with PGx guidance; many trials limited by risk of bias, lack of blinding, or heterogeneity
CPIC guideline (Bousman et al., 2023)	Provides actionable gene‑drug dosing guidance for specific genes (CYP2D6, CYP2C19, CYP2B6) for SSRIs/tricyclics but does not endorse multi‑gene panels (≥5 genes)
PrismRA / MSRC evidence (Curtis, Strand, Mellors, Hayes assessments)	PrismRA shows analytic/clinical validity in nonrandomized cohorts and decision‑impact studies but evidence rated very low quality with potential bias; clinical utility not proven

Definitions:

Multi-Gene Panel: Genetic tests that use next-generation sequencing to test multiple genes simultaneously; also called multigene test, multiple-gene panel test, and multiple-gene test.

PGx: Pharmacogenetic testing; genetic testing to guide medication selection/dosing based on gene–drug interactions.

PrismRA / MSRC: Molecular signature response classifier (Scipher Medicine) intended to predict non-response to anti‑TNF therapy in rheumatoid arthritis.

Pharmacogenetic (PGx) multi-gene panel: Genetic testing that assesses multiple genes simultaneously to inform medication selection or dosing; the document notes lack of CPIC recommendations for panels including five or more genes.

Revision History

2026-03-01material_changeLatest

2026-03-01removed

Archived previous policy version CS149KS.01 (Supporting Information change documented 03/01/2026).

clarification

Policy explicitly states it applies only to the state of Kansas and directs providers to the Kansas Medical Assistance Program Professional Fee-for-Service Provider Manual for state-specific medical necessity criteria; policy also includes a negative coverage statement that multi-gene panels (five or more genes) and the PrismRA® test are unproven and not medically necessary.

Policy Summary

PayerUnitedHealthcare

PolicyPharmacogenetic Panel Testing (for Kansas Only)

Policy CodePolicy CS149KS.02

Change TypeClarified / Added / Removed

Effective DateMarch 1, 2026

Next Review Date

On This Page

Multi-gene panels (>=5 genes) not medically necessary: 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.Multi-Gene Panel = five or more genes

Policy-level negative stance on multi-gene panels (>=5 genes).

PrismRA not medically necessary: 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.

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General evidence-based coverage considerations

Coverage determinations reference evidence strength by indication; panel testing supported only where evidence demonstrates clinical utility:

Cardiac conditions / cardiac interventions: PGx testing has potential opportunities (PCI studies show actionable prescribing opportunities), but additional high-quality studies needed to establish clinical utility.
Ratner et al. (2022); Rouby et al. (2020)
Anthracycline-induced cardiotoxicity (CIC): Routine use of PGx panel testing for CIC risk assessment is not supported by current evidence; further prospective studies with long-term follow-up required.
Yang et al. (2021); Stafford et al. (2024); Sági et al. (2018)
Pain management: Evidence for multi-gene PGx panel testing to predict response, side effects, dependence, or improve outcomes is evolving but currently insufficient and not broadly supported as safe or efficacious.
Multiple RCTs and reviews with mixed results (Kraus 2024; Agulló 2023; Hamilton 2022; Rodriguez 2021; Hayes evaluations)
Rheumatoid arthritis (PrismRA/MSRC): Evidence is limited and of very low quality; PrismRA has preliminary analytic/clinical validity but requires larger independent studies; clinical utility not proven.
Hayes assessment D2; Curtis et al.; Mellors et al.
Other multi-gene PGx panel uses: Uses for multimorbidity, polypharmacy, cancer treatment toxicity, IBD, and general prescribing have insufficient evidence for routine use; some trials/meta-analyses show reduced adverse events but additional robust/diverse studies required.
PREPARE, Lingaratnam meta-analysis, David et al., O'Shea review

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Coverage Rationale / Non State-Specific Criteria

Policy modified to direct use of external InterQual criteria for medical necessity determination:

Refer to InterQual for psychotropic PGx medical necessity: Refer to InterQual® CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response for medical necessity clinical coverage criteria for pharmacogenetic testing.
This instruction was added 03/01/2026 per Policy History

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Clinical evidence summary (informational criteria / limitations)

Evidence and guideline context summarized; no explicit internal coverage criteria for multi-gene panels (>=5 genes) provided in this part:

Systematic reviews and trials show mixed evidence; some trials/meta-analyses suggest increased medication changes and possible reduced all-cause hospitalization but heterogeneity and limited high-quality long-term data prevent generalized conclusions.
David et al.; O'Shea et al.; PREPARE; meta-analyses
CPIC guidance limited to single genes: CPIC provides actionable gene-drug guidance for specific single genes (e.g., CYP2D6, CYP2C19, CYP2B6) but does not provide recommendations specific to multi-gene panels including five or more genes.
CPIC guidance 2023 notes no recommendations for panels >=5 genes
Professional society positions: Professional societies (ACR, EULAR, ISPG, NCCN, STRIPE) generally note potential utility for specific gene-drug pairs and research gaps; many guidelines do not address panel testing or recommend routine multi-gene panel use.
ACR, EULAR, ISPG, NCCN, STRIPE conclusions

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Documentation Required

Use evidence to justify PGx panel testing

Document the clinical rationale and cite indication-specific evidence when ordering multi-gene PGx panel testing. Note that current evidence does not support routine panel testing for certain indications including assessment of anthracycline-induced cardiotoxicity and broad/general pain management.

Prior Authorization

Prior authorization implication (implicit)

Prior authorization may be required and testing may be denied when ordered for indications that lack sufficient evidence of clinical utility unless adequate justification and supporting evidence are provided.

Routine chronic non-cancer pain (CNCP) panel testing
General multimorbidity or broad, preemptive multi-gene panels without indication-specific justification

Documentation Required

Use InterQual criteria for psychotropic PGx testing determinations

Providers and reviewers must use InterQual® CP: Molecular Diagnostics, Pharmacogenomic Testing for Psychotropic Medication Drug Response when assessing medical necessity for pharmacogenetic testing related to psychotropic medication response.

Documentation Required

Apply federal/state/contractual benefit terms

When determining coverage, check applicable federal, state, or contractual benefit plan requirements because those terms govern in the event of any conflict with this policy.