CurrentPremera BluecrossPolicy 2.04.520

Investigational laboratory and molecular tests (miscellaneous list)

Lists laboratory and molecular diagnostic tests considered investigational due to insufficient evidence of clinical benefit; applies to providers ordering or billing under Premera benefit plans.

Policy Summary

PayerPremera Bluecross

PolicyInvestigational laboratory and molecular tests (miscellaneous list)

Policy CodePolicy 2.04.520

Change TypeNo material clinical or coverage changes

Effective DateJan 1, 2026

Next Review Date

Key ActionDo not request prior authorization for tests designated investigational; document clinical validity and utility when seeking coverage or reference a separate test-specific policy if one exists.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

~150+investigational codes listed

Nationalpolicy scope

07/01/25-04/01/26new code dates

unchangedrecent review

Coverage Criteria — Investigational / Not Medically Necessary

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Investigational/Not Medically Necessary

Covered when ALL of the following are met

Investigational stance: All tests listed in this policy are considered investigational as there is insufficient evidence to determine that the technology results in an improvement in the net health outcome.

Tests in the coding tables are designated investigational.

Investigational / Not Medically Necessary by default

Covered only when a separate policy specifies coverage; otherwise considered investigational

Investigational tests default: When a test is not addressed in a separate policy and has limited evidence of clinical utility, it is considered investigational and not covered.

Tests with insufficient published data, unclear placement in the clinical pathway, no demonstrated impact on management or outcomes, or lacking decision thresholds are considered investigational.

If a different Premera policy specifically addresses the same laboratory test, that policy’s conclusions take precedence and supersede the statements in this policy. The Introduction and Description clarify that this document applies only to tests not already covered by a separate, test‑specific policy; when a separate policy exists, follow the criteria in that policy.

Tests included in this policy are considered investigational primarily due to an insufficient evidence of clinical utility. Typical reasons include limited or no published data, unclear placement in the clinical pathway, lack of demonstrated impact on management or outcomes, or absence of decision thresholds that would change patient care.

Covered indications — none listed; tests designated investigational

Covered indications: None listed — no covered indications are specified in this policy; tests included in the coding tables are designated investigational and not covered.

If a separate Premera policy addresses a specific test, that policy supersedes the conclusions in this policy.

None specified — tests in this policy considered investigational for diagnostic/prognostic/therapeutic/future risk

Investigational scope: No specific indications are provided — tests in this policy are considered investigational for diagnostic, prognostic, therapeutic, or future risk assessment uses due to insufficient evidence of clinical utility.

Tests may be reconsidered if sufficient evidence accumulates or if a separate policy is developed for a specific test.

Coding — CPT / PLA / Other Procedure Codes

Investigational CPT/PLA codes (sample from list)CPTNot Covered

0002U	Oncology (colorectal), quantitative assessment of three urine metabolites by LC-MS/MS, algorithm reported as likelihood of adenomatous polyps (PolypDX).
0016M	Oncology (bladder), mRNA microarray gene expression profiling of 209 genes, FFPE tissue, algorithm reported as molecular subtype (Decipher Bladder TURBT+G54).
0019M	Cardiovascular disease, plasma, analysis of protein biomarkers by aptamer-based microarray and algorithm reported as 4-year likelihood of coronary event.
0112U	Infectious agent detection and identification, targeted sequence analysis (16S and 18S rRNA genes) with drug-resistance gene (MicroGenDx).
0163U	Oncology (colorectal) screening, ELISA of 3 plasma/serum proteins with demographic data (BeScreened-CRC).

Investigational CPT/PLA codes (continued)CPTNot Covered

0174U	Oncology (solid tumor), mass spectrometric 30 protein targets, FFPE tissue, prognostic and predictive algorithm.
0176U	Cytolethal distending toxin B (CdtB) and vinculin IgG antibodies by immunoassay (IBSchek).
0180U	Red cell antigen (ABO) genotyping, Sanger sequencing (Navigator ABO Sequencing).
0181U	Red cell antigen (Colton) genotyping (Navigator CO Sequencing).
0182U	Red cell antigen (Cromer) genotyping (Navigator CROM Sequencing).
0183U	Red cell antigen (Diego) genotyping (Navigator DI Sequencing).
0184U	Red cell antigen (Dombrock) genotyping (Navigator DO Sequencing).
0185U	Red cell antigen (H) genotyping (Navigator FUT1 Sequencing).
0186U	Red cell antigen (H) genotyping (FUT2) (Navigator FUT2 Sequencing).
0187U	Red cell antigen (Duffy) genotyping (Navigator FY Sequencing).

1–10 of 15

1/2

Listed procedure/test codesmixed

0522U	Carbonic anhydrase VI, parotid specific/secretory protein and salivary protein 1 (SP1), IgG, IgM, and IgA antibodies, chemiluminescence, semiqualitative, blood
0525U	Oncology, spheroid cell culture, 11-drug panel ... ovarian, fallopian, or peritoneal response prediction for each drug
0528U	Lower respiratory tract infectious agent detection, 18 bacteria, 8 viruses, and 7 antimicrobial-resistance genes, amplified probe technique...
0531U	Infectious disease (acid-fast bacteria and invasive fungi), DNA (673 organisms), next-generation sequencing, plasma
0535U	Perfluoroalkyl substances (PFAS) by LC-MS/MS, plasma or serum, quantitative
0541U	Cholesterol efflux capacity, LC-MS/MS measurement of 5 HDL-bound apolipoproteins, algorithm reported as pCAD score
0542U	Nephrology renal transplant, urine NMR of 84 urinary metabolites combined with other data, algorithm probability for allograft injury
0545U	Acetylcholine receptor antibody identification by immunofluorescence, live cells
0546U	LRP4 antibody identification by immunofluorescence, live cells
0548U	Glial fibrillary acidic protein (GFAP), chemiluminescent enzyme immunoassay, plasma

1–10 of 57

1/6

Policy-related CPT codes (added/removed across history)CPT

0112U
0365U
0366U
0367U
0406U
0415U
0418U
0371U
0372U
0373U

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1/15

Minimum protein panel size examples

Examples of minimum protein panel sizesPanel sizes cited in policy examples include assays measuring ~10, ~30, ~142, and ~388 proteins, depending on the specific test/assay.

Context for variabilityProtein panel size varies by intended analytes and assay platform (mass spectrometry, immunoassay, multiplex), as shown in listed codes/descriptions.

Use in coding descriptionsSeveral CPT/PLA code descriptors in the coding section reference specific protein counts for assays (see code descriptions for exact panel sizes).

New code effective dates

Range of new code effective datesNew CPT/PLA codes listed in the policy have effective dates ranging from 07/01/25 through 04/01/26.

Examples of 07/01/25 effective codesCodes effective 07/01/25 include 0570U, 0571U, 0572U, 0573U, and 0574U (see coding descriptions).

Examples of 10/01/25 and later codesCodes effective 10/01/25 include 0577U and 0579U; codes effective 01/01/26 and 04/01/26 are also listed (see full code list).

CLIA complexity — high-complexity testing

CLIA complexity requirementLaboratories that offer laboratory-developed tests (LDTs) must be licensed by CLIA for high-complexity testing.

Regulatory expectationLDTs must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA).

FDA status notedThe policy notes the U.S. FDA has chosen not to require regulatory review of these LDTs to date.

Provider Actions — Prior Authorization, Documentation, Denial Risk

Prior Authorization

Coverage default & Benefit Verification

If there is no separate policy that addresses a specific test, the coverage default is that the test is considered investigational due to insufficient evidence of clinical utility. Investigational status may lead to claim denial. Providers should verify member benefits and any plan-specific limits prior to ordering tests.

Coverage default: Tests not addressed in a separate policy = investigational
Investigational tests may be denied for lack of demonstrated clinical utility
Verify member benefits and plan-specific coverage limits before ordering

Denial Risk

Investigational tests — potential denial and denial risk

Tests listed in this policy are considered investigational because there is insufficient evidence that they improve net health outcomes. Investigational tests are at increased risk for denial when documentation does not establish clinical validity and clinical utility or when the test’s role in the clinical pathway is unclear.

All tests listed in this policy = investigational
Denial risk increases when evidence of clinical utility is limited or absent
Proprietary tests with no independent validation are higher risk for denial

Documentation Required

Provider documentation expectations

Providers must document the clinical validity and clinical utility of the ordered test in the member’s medical record. Documentation should explain how the test result will affect clinical management and lead to improved outcomes compared with existing standard care.

Document clinical validity (supporting studies, test performance characteristics)
Document clinical utility (how results change management and improve outcomes)
If available, include independent validation data and peer‑reviewed evidence

Documentation Required

Documentation — where the test fits in the clinical pathway

When ordering a test, describe where the test fits in the clinical pathway (replacement, triage, or add‑on), the intended use, and how decision thresholds will be applied. If thresholds or decision rules are not established, include rationale for how results would be interpreted and acted upon.

State intended use and clinical pathway position (replacement, triage, add‑on)
Provide decision thresholds or describe how results will guide management
Explain alternatives and why the investigational test is being used

Note

Benefit verification and member-level documentation

Benefit verification at the member level is required. Coverage is subject to the member’s benefit plan limits and conditions. Members and providers should consult the member benefit booklet or contact customer service to determine whether the test is a covered service under the specific plan. This policy does not apply to Medicare Advantage.

Consult member benefit booklet or customer service for coverage details
Coverage is determined by the specific member benefit plan and limits
This policy is not applicable to Medicare Advantage members

Note

CLIA licensing and regulatory considerations for LDTs

Laboratory‑developed tests (LDTs) must comply with CLIA licensing for high‑complexity testing. The FDA has not required premarket review of these tests to date; independent validation and peer‑reviewed evidence should be provided when available to support clinical validity and utility.

LDTs require CLIA high‑complexity laboratory licensure
Provide independent validation data when available to support coverage consideration

Definitions — Key Terms

Investigational — definition

Investigational — definitionTests for which there is insufficient evidence to determine that the technology results in an improvement in net health outcome; included tests are often in a developmental phase with limited evidence of clinical utility for diagnosis, prognosis, or risk assessment.

Superseding policy noteIf a separate Premera policy addresses the same test, that policy's conclusions supersede this investigational policy.

Implication for coverageTests designated investigational in this policy are considered not medically necessary absent supporting evidence or a separate policy that permits coverage.

Laboratory-developed test (LDT) — definition

LDT — core definitionA clinical laboratory test developed and validated by a laboratory and offered as a service; these tests are often available clinically before an evidence base establishes clinical validity and utility.

Evidence contextBecause many LDTs are proprietary, independent evaluation data may be limited in early stages; tests listed are often in a developmental phase with limited clinical utility evidence.

Policy applicabilityThis policy applies when no separate medical-necessity policy exists for the test; separate test-specific policies supersede this guidance.

Laboratory-developed test (LDT) — regulatory definition

LDT — CLIA regulatory noteLaboratory-developed tests are subject to CLIA regulation; laboratories offering LDTs must meet CLIA general regulatory standards and be licensed for high-complexity testing.

Marketing/practice contextClinical laboratories may develop and validate tests in-house and market them as a laboratory service.

FDA positionThe policy notes the U.S. Food and Drug Administration has chosen not to require regulatory review of these tests to date.

Ordering Requirements

Note

Ordering guidance intended for providers — no specific ordering restrictions listed

This policy is written for providers and does not list specific ordering restrictions (such as provider type); follow the policy’s investigational designations when ordering.

Billing Rule

No specified ordering provider — labs must meet CLIA requirements

The policy does not specify who may order the tests; however, laboratories offering these tests must meet CLIA high‑complexity requirements per regulatory expectations.

No provider-type ordering restriction is specified in the policy excerpts.
Confirm laboratory CLIA high‑complexity certification for tests developed/validated in‑house.

Not Covered — Investigational Tests

All procedure and test codes listed in the coding tables are considered investigational and, as such, are not covered under this policy.

The tests listed in this policy are not covered because they have not demonstrated clinical utility—meaning there is insufficient evidence that use of the test alters clinical management in a way that improves health outcomes.

Policy Summary

PayerPremera Bluecross

PolicyInvestigational laboratory and molecular tests (miscellaneous list)

Policy CodePolicy 2.04.520

Change TypeNo material clinical or coverage changes

Effective DateJan 1, 2026

Next Review Date

SourceLink

On This Page

OpenPayer

Investigational laboratory and molecular tests (miscellaneous list)

Coverage Criteria — Investigational / Not Medically Necessary

Coding — CPT / PLA / Other Procedure Codes

Provider Actions — Prior Authorization, Documentation, Denial Risk

Definitions — Key Terms

Background — Scope and Test Modalities

Ordering Requirements

Not Covered — Investigational Tests