CurrentUnitedHealthcarePolicy 2026T0587X

Pharmacogenetic Panel Testing

UnitedHealthcare Commercial and Individual Exchange medical policy governing the use of pharmacogenetic multi-gene panels (≥5 genes) and the PrismRA molecular signature test for evaluating drug-metabolizer status and predicting anti-TNF response in rheumatoid arthritis.

Policy Summary

PayerUnitedHealthcare

PolicyPharmacogenetic Panel Testing

Policy CodePolicy 2026T0587X

Change TypeTemplate Update (shared policy creation)

Effective DateJanuary 1, 2026

Next Review Date

Key ActionDo not submit claims for pharmacogenetic multi-gene panel tests (≥5 genes) for evaluation of drug-metabolizer status as they are considered unproven and not medically necessary under this policy; if submitted, documentation should justify clinical utility and supporting evidence.

POLICY UPDATE CHANGES

01/01/2026 Template Update: Created shared policy version to support application to Oxford plan membership and archived previous policy version 2025T0587W and LABORATORY 023.23.

Not coveredPolicy Position - Multi-Gene Panels

Not coveredPolicy Position - PrismRA

10+Genes referenced across studies

1Policy history entries

Coverage Summary

Policy 2026T0587X (effective January 1, 2026) applies to UnitedHealthcare Commercial and Individual Exchange plans and states that pharmacogenetic Multi-Gene Panels (defined here as tests of five or more genes) for evaluation of drug-metabolizer status are unproven and not medically necessary due to insufficient evidence of efficacy. The policy also finds the PrismRA molecular signature test to predict anti‑TNF nonresponse in rheumatoid arthritis to be unproven and not medically necessary for evaluating likelihood of inadequate response to anti‑TNF therapies.

Key quick facts

Policy Position - Multi-Gene PanelsNot covered / Unproven (multi-gene panels ≥5 genes)

Policy Position - PrismRANot covered / Unproven for predicting anti-TNF nonresponse in RA

PrismRA threshold>= 11.8 (used to identify high/very-high likelihood of poor response/nonresponse to anti-TNF)

ACR50 threshold>= 50% improvement used as primary clinical response endpoint

Genes referenced across studies10+

Medical‑Necessity Criteria

Coverage Rationale - Multi-Gene Panels

Covered when ALL of the following are met:

{

"operator":"all",

"children":[

{"text":"Multi-Gene Panel: Genetic tests that typically use next-generation sequencing to test multiple genes simultaneously; also called multigene test, multiple-gene panel test, and multiple-gene test (National Cancer Institute Dictionary of Genetics Terms, 2025)."},

{"text":"Use: Multi-Gene Panels (five or more genes) proposed for the evaluation of drug-metabolizer status."},

Determination: 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.

Policy note: Multi-Gene Panels include tests that report metabolizer status and gene-drug interactions across multiple medications; single-gene or targeted multi-gene testing for specific drug-gene pairs (e.g., CYP2C19 for clopidogrel) are evaluated separately.

]

}

Coverage Rationale - PrismRA

Covered when ALL of the following are met:

{

"operator":"all",

"children":[

{"text":"Test: PrismRA® molecular signature test."},

{"text":"Use: PrismRA is proposed for evaluating likelihood of inadequate response to anti-TNF therapies for rheumatoid arthritis."},

Determination: 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.

Policy note: Clinical decisions about anti-TNF therapy should be guided by established clinical assessment and guideline-directed care rather than PrismRA testing.

Evidence & Guideline Considerations

Evidence & Guideline Considerations - summary conclusions to inform interpretation of the above criteria:

{

"operator":"all",

"children":[

{"text":"General evidence: Published randomized controlled trials and systematic reviews provide mixed results for clinical utility of combinatorial pharmacogenetic panels; some RCTs and meta-analyses suggest modest improvements in response or remission for certain psychiatric populations, but limitations include heterogeneity of assays, populations, and outcomes."},

{"text":"Panel size effect: Cumulative analyses indicate larger PGx panels may yield diminishing clinical returns compared with smaller, targeted gene testing."},

Applicable Codes

Not covered / Cosmetic or Unproven CodesmixedNot Covered

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, 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 21

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Provider Actions & Documentation

Documentation Required

Medical necessity documentation for Multi-Gene Panels

Do not submit claims for pharmacogenetic multi-gene panel tests (≥5 genes) for evaluation of drug-metabolizer status as they are considered unproven and not medically necessary under this policy; if submitted, documentation should justify clinical utility and supporting evidence.

0029U
0173U
0175U
0345U
0347U
0348U
0349U
0350U
0392U
0411U
0419U
0423U
0434U
0438U
0460U
0461U
0476U
0477U
0516U
0533U
81418

Documentation Required

Use caution integrating PrismRA results

Providers should note limitations of PrismRA evidence (nonrandomized validation, limited racial diversity, potential conflicts of interest) and document clinical rationale when deviating from standard guidelines if using PrismRA to guide therapy.

Documentation Required

Interpret PGx panel results per existing gene-drug guidelines

When single-gene actionable results (e.g., CPIC gene-drug pairs) are available from testing, providers should apply CPIC/other guideline recommendations and document how results informed prescribing decisions.

Documentation Required

Reference member-specific benefit plan

When deciding coverage, reference the member specific benefit plan document as its terms govern in the event of conflict with this policy.

Documentation Required

Check federal/state mandates and Medicare guidance

Before using the policy, check the member specific benefit plan and any applicable federal or state mandates; in absence of Medicare NCD/LCD guidance, MAOs may create coverage determinations using objective evidence-based rationale.

Documentation Required

Use of third-party tools

UnitedHealthcare may use tools developed by third parties (e.g., InterQual® criteria) to assist in administering health benefits.

Background & Evidence Summary

Pharmacogenetics (PGx) studies how genetic variation affects medication response and adverse effects; PGx tests can be single‑gene or multi‑gene panels. Multi‑gene panels in this policy are tests that typically use next‑generation sequencing to assess multiple genes simultaneously, generally five or more genes, and are intended to guide treatment strategies. The policy focuses on multi‑gene PGx panels and reviews evidence across psychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, and ADHD) as well as other areas including cardiovascular care (PCI), pain management, oncology/chemotherapy toxicity (anthracycline and fluoropyrimidine toxicity), multimorbidity/polypharmacy, and the PrismRA molecular signature classifier for rheumatoid arthritis.

Evidence Item	Summary
Guideline / Evidence summary	Policy cites multiple systematic reviews, meta-analyses, RCTs, Hayes evaluations, and health technology assessments noting inconsistent evidence and methodological limitations; overall insufficient evidence to support clinical utility of multi-gene panels.
Key coded tests listed	Multiple U-codes and CPT 81418 represent multi-gene pharmacogenomic panels (6+ genes) referenced in policy (examples: 0029U, 0173U, 0345U, 0423U, 0438U, 0516U, 0533U, 81418).
PREPARE trial ADR reduction (12-gene panel)	In the PREPARE 12-gene study, among participants with actionable results, clinically significant ADRs occurred in 21% (experimental) vs 27.7% (control) (OR 0.70; p=0.0075); overall ADR incidence also lower in PGx group.
PrismRA evidence highlights	PrismRA/MSRC studies and decision models report improved alignment and outcomes (e.g., MSRC-aligned CDAI LDA/REM 36.0% vs 21.9%, OR 2.01; ACR50 mean 39.6% in PrismRA-consistent-treated; Mellors cross-cohort validation PPV 89.8%, specificity 86.8%); Hayes rates evidence very low and notes limitations in study design and generalizability.
Recent systematic reviews / RCTs	Multiple recent meta-analyses and RCTs (2017–2025) report mixed results: some show improved early response/remission with PGx-guided antidepressant treatment while others note heterogeneity, bias, and lack of persistent benefit at later timepoints; overall evidence described as inconsistent and limited.

Definitions

Multi-Gene PanelGenetic tests that typically use next-generation sequencing to test multiple genes simultaneously; also called multigene test (panels in this policy = five or more genes).

PGxPharmacogenomic; genetic testing to inform medication selection and dosing.

MSRC / PrismRAMolecular signature response classifier — a proprietary test combining gene expression, serologic marker(s), and clinical metrics to predict nonresponse to anti-TNF therapy in rheumatoid arthritis.

CPICClinical Pharmacogenetics Implementation Consortium — provides gene-drug clinical practice guidelines.

ACR50American College of Rheumatology criteria for ≥50% improvement in RA disease activity (used as clinical response endpoint).

Policy Summary

PayerUnitedHealthcare

PolicyPharmacogenetic Panel Testing

Policy CodePolicy 2026T0587X

Change TypeTemplate Update (shared policy creation)

Effective DateJanuary 1, 2026

Next Review Date

On This Page

OpenPayer

Pharmacogenetic Panel Testing

Coverage Summary

Medical‑Necessity Criteria

Applicable Codes

Provider Actions & Documentation

Background & Evidence Summary

Revision History