Premera Bluecross investigational lab tests Coverage

Coverage Criteria — Investigational Laboratory Tests

Investigational — Not covered as medically necessary

Covered when ALL of the following are met

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

If another Premera policy reviews the same test, that policy's conclusions supersede this policy.

Investigational/Not Medically Necessary group

Covered when ALL of the following are met

Investigational determination: Test is not addressed in a separate policy AND evidence demonstrates sufficient clinical utility (clinical validity and impact on management leading to improved net health outcome).

Currently, for tests listed here, evidence is insufficient; thus they are designated investigational.

Investigational / Not Medically Necessary

Covered when ALL of the following are met

Investigational status: All tests listed in this policy are considered investigational

Investigational tests are not considered medically necessary for coverage determinations unless otherwise stated in plan benefits

If another Premera policy specifically evaluates the same laboratory test, the conclusions of that specific policy take precedence over the determinations in this investigational policy. This policy is intended to address tests that are not covered by a separate, dedicated policy; when overlap exists, the separate policy’s criteria govern coverage decisions.

Tests that are the subject of a separate Premera medical policy are excluded from this policy and are governed by their own policy language and criteria. This document applies only to tests not already addressed elsewhere; if a separate policy exists for a test, that policy supersedes the guidance here.

This medical policy does not apply to Medicare Advantage members. Coverage determinations for Medicare Advantage enrollees follow applicable Medicare rules and member benefit provisions.

Tests listed in this policy are designated investigational because there is insufficient evidence that use of the technology leads to an improvement in net health outcome. As investigational tests, they are not considered medically necessary for coverage determinations under this policy unless otherwise stated in a separate policy.

The primary reason tests are considered investigational in this policy is insufficient clinical utility. Contributing factors include limited or no published data, unclear placement in the clinical pathway (replacement, triage, or add-on), uncertain impact on clinical management, lack of established decision thresholds, and absence of evidence showing meaningful patient outcome improvement.

All tests enumerated in this policy are considered investigational. As a result, these tests are not supported by this policy as medically necessary for coverage given the current evidence.

COVERED INDICATIONS — no specific clinical indications render these tests covered

No covered indications: No specific clinical indications are provided that would render these tests covered; the policy treats the listed tests as investigational.

Providers should refer to separate, specific policies if available (those supersede this policy).

COVERED INDICATIONS — no indications specified as covered; tests without dedicated policies treated investigational

No covered indications specified: No indications are specified as covered in this policy; tests without dedicated policies are treated as investigational due to insufficient evidence of clinical utility.

If a separate policy exists for a given test, that policy's criteria apply instead.

COVERED INDICATIONS — document contains vendor and clinical references for specialty tests

Vendor and literature references: Document cites multiple vendor and clinical references for specialty tests (examples: MicroGenDx, APOL1 genotyping, Oncuria, NaviDKD, PromarkerD) but does not specify any of these as covered indications within this policy.

References are provided for informational context only and do not imply medical necessity or coverage.

Coding — Affected CPT/HCPCS/Proprietary Codes

Listed investigational codes (sample)mixedNot Covered

0002U	Oncology (colorectal), quantitative assessment of three urine metabolites (ascorbic acid, succinic acid and carnitine) 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 in high-risk populations
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, algorithm reported as likelihood of CRC or advanced adenomas (BeScreened-CRC)
0174U	Oncology (solid tumor), mass spectrometric 30 protein targets, FFPE tissue, prognostic/predictive algorithm (LC-MS/MS Targeted Proteomic Assay)

Additional listed investigational codes (partial list)mixedNot Covered

0176U	CdtB and vinculin IgG antibodies by immunoassay (IBSchek)
0180U	Red cell antigen (ABO) genotyping (Navigator ABO Sequencing) and multiple Navigator blood group sequencing codes (0181U–0201U, etc.)
0210U	Syphilis test; non-treponemal antibody, immunoassay, quantitative (RPR) (BioPlex 2200 RPR Assay)
0219U	HIV targeted viral next-generation sequence analysis, algorithm reported as prediction of antiviral drug susceptibility (Sentosa SQ HIV-1 Genotyping Assay)
0220U	Oncology (breast cancer), image analysis with AI assessment of 12 histologic/IHC features, reported as recurrence score (PreciseDx Breast Cancer Test)
0295U	Oncology (breast DCIS), protein expression profiling with clinicopathologic factors, algorithm reported as a recurrence risk score (DCISionRT, PreludeDX)
0337U	Oncology (plasma cell disorders/myeloma), circulating plasma cell selection/identification/enumeration (CELLSEARCH CMMC Test)
0342U	Oncology (pancreatic), multiplex immunoassay of multiple proteins with algorithm reported qualitatively (IMMray PanCan-d)
0344U	Hepatology (NAFLD), semiquantitative evaluation of 28 lipid markers by LC-MS/MS reported as at-risk for NASH (OWLiver)
0365U	Oncology (bladder), analysis of 10 protein biomarkers by immunoassays, urine, algorithm reported as probability of bladder cancer (Oncuria Detect)

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Listed new/updated CPT-category I/III or proprietary codes (part 1)mixed

0522U	Carbonic anhydrase VI, parotid specific/secretory protein and salivary protein 1 (SP1) IgG, IgM, and IgA antibodies, chemiluminescence; semiqualitative; blood (new code effective 01/01/25).
0525U	Oncology, spheroid cell culture; 11-drug panel ... ovarian, fallopian, or peritoneal response prediction for each drug (new code effective 01/01/25).
0528U	Lower respiratory tract infectious agent detection, 18 bacteria, 8 viruses, and 7 antimicrobial-resistance genes ... (new code effective 01/01/25).
0531U	Infectious disease (acid-fast bacteria and invasive fungi), DNA (673 organisms), next-generation sequencing, plasma (new code effective 04/01/25).
0535U	Perfluoroalkyl substances (PFAS) ... by LC-MS/MS plasma or serum; quantitative (new code effective 04/01/25).
0541U	Cardiovascular disease (HDL reverse cholesterol transport), cholesterol efflux capacity, LC-MS/MS ... algorithm reported as prediction of coronary artery disease (pCAD) score (new code effective 04/01/25).

Listed new/updated CPT-category I/III or proprietary codes (part 2)mixed

0542U	Nephrology (renal transplant), urine, NMR measurement of 84 urinary metabolites ... algorithm reported as a probability score for allograft injury status (new code effective 04/01/25).
0545U	Acetylcholine receptor (AChR), antibody identification by immunofluorescence; using live cells, reported as positive or negative (new code effective 04/01/25).
0546U	Low-density lipoprotein receptor-related protein 4 (LRPA), antibody identification by immunofluorescence; using live cells, reported as positive or negative (new code effective 04/01/25).
0548U	Glial fibrillary acidic protein (GFAP) chemiluminescent enzyme immunoassay, using plasma (new code effective 04/01/25).
0550U	Oncology (prostate), ELISA for total PSA and free PSA ... algorithm reported as a risk score for high-grade prostate cancer (new code effective 04/01/25).
0558U	Oncology (colorectal), quantitative ELISA for secreted colorectal cancer marker (BF7 antigen) ... (new code effective 07/01/25).
0559U	Oncology (breast), quantitative ELISA for BF9 antigen ... (new code effective 07/01/25).
0563U	Infectious disease (bacterial and/or viral respiratory), pathogen-specific nucleic acid, 11 viral targets and 4 bacterial targets, qualitative RT-PCR, upper respiratory specimen (new code effective 07/01/25).
0564U	Infectious disease, pathogen-specific nucleic acid 10 viral targets and 4 bacterial targets, qualitative RT-PCR, upper respiratory specimen (new code effective 07/01/25).
0570U	Neurology (traumatic brain injury), GFAP and UCH-L1 immunoassay, whole blood or plasma, components reported elevated/non-elevated (new code effective 07/01/25).

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Policy CPT/HCPCS codes (history additions/removals)CPT

0112U	CPT code added per history
0365U	CPT code added per history
0366U	CPT code added per history
0367U	CPT code added per history
0406U	CPT code added per history
0415U	CPT code added per history
0418U	CPT code added per history
0371U	CPT code added per history
0372U	CPT code added per history
0373U	CPT code added per history

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inv-15: New code effective dates

New codes effective 01/01/2025Examples: 0522U, 0525U, 0528U (listed as new code effective 01/01/25)

New codes effective 04/01/2025Examples: 0531U, 0535U, 0541U, 0542U, 0545U, 0546U, 0548U (listed as new code effective 04/01/25)

New codes effective 07/01/2025Examples: 0558U, 0559U, 0563U, 0564U, 0570U, 0571U, 0572U, 0573U, 0574U (listed as new code effective 07/01/25)

New codes effective 10/01/2025Examples: 0577U, 0579U, 0581U, 0584U, 0587U, 0588U, 0589U, 0590U, 0591U, 0593U, 0594U, 0595U, 0598U, 0599U (listed with 10/01/25 effective dates in code groups/history)

inv-16: Test reporting thresholds and decision points

Provider Actions — Prior Authorization, Documentation, and Denial Risk

Prior Authorization

Benefit Verification and Denial Risk

All tests listed in this policy are considered investigational and may be denied as not medically necessary. Before ordering any test addressed by this policy, providers must verify member benefits and coverage details with the payer. Coverage can vary by contract and investigational status may result in claim denial or member cost-sharing. Providers should confirm prior authorization requirements and medical necessity criteria with the member's plan, when applicable.

Benefit verification required prior to testing
Investigational tests listed in this policy may be denied as not medically necessary
Confirm any prior authorization or medical review requirements with the member's plan

Documentation Required

Documentation Requirements

Maintain complete clinical documentation supporting the medical necessity of the test, including indication, prior testing, and how the result will change patient management. Documentation should be available for medical review when requested.

Not Covered — Investigational Tests

Because the tests listed in this policy are considered investigational, they are not covered as medically necessary under this policy. Providers should anticipate that claims for these services may be denied on the basis of insufficient evidence of clinical benefit.

These tests are deemed investigational and not covered because the evidence is insufficient to establish clinical utility — for example, when published data are limited or non-evaluable, when the test’s role in patient management is unclear, or when decision thresholds and outcome benefits have not been demonstrated.

Tests listed as investigational in this policy are not considered medically necessary for coverage determinations under this policy. The policy history and coverage stance document that all tests listed are investigational and therefore are not covered absent new evidence or a separate policy stating otherwise.

Background and Scope

This policy focuses on commercially available genetic, molecular, and other laboratory tests that diagnose disease or predict future health risks but currently lack sufficient evidence of clinical utility. The policy is intended as guidance for providers in clinical settings and emphasizes that many of these proprietary or early‑stage tests have limited independent evaluation data; therefore, their impact on clinical management and patient outcomes has not been established.

Definitions

inv-31: Investigational definition

Investigational (definition)Tests included in this policy are considered investigational because there is insufficient evidence that the technology results in an improvement in net health outcome.

Coverage implicationInvestigational tests are not considered medically necessary for coverage determinations unless otherwise stated in plan benefits.

Policy precedenceIf another Premera policy reviews the same test, that policy's conclusions supersede this investigational policy.

inv-32: Laboratory-developed test (LDT) definition

Laboratory‑developed test (LDT) definitionA test developed and validated in‑house by a clinical laboratory and marketed as a laboratory service; must meet CLIA regulatory standards and CLIA high‑complexity licensing requirements.

Regulatory oversight

Frequency Limits

inv-37: FREQUENCY LIMITS (placeholder key_value)

No frequency limits specifiedThe policy does not specify numerical frequency limits for investigational tests in the Frequency Limits section.

Ordering guidance remains provider‑dependentOrdering and coverage depend on member benefit plan and company procedures; no clinician‑type ordering restrictions are detailed.

Refer to prior‑authorization processesProviders should expect investigational tests to require medical review and be subject to prior authorization or denial as not medically necessary.

inv-38: FREQUENCY LIMITS (placeholder key_value)

Frequency limits not defined per testFor tests moved into or added to this policy, the document does not establish per‑test repeat intervals or time‑based limits in the Frequency Limits section.

Benefit plan may impose limits

Ordering Requirements

Note

No specific ordering provider restrictions noted

This policy is intended for providers in hospitals, clinics, or laboratories; no specific ordering clinician-type restrictions are specified in the document.

Documentation Required

LDTs require CLIA-compliant laboratory

Laboratory‑developed tests (LDTs) must meet CLIA general regulatory standards and laboratories offering them must be CLIA‑licensed for high‑complexity testing.

Confirm the performing laboratory holds CLIA high‑complexity licensure prior to ordering.

Billing Rule

OpenPayer

Laboratory Testing — Investigational Services (Investigational Laboratory Tests)

Coverage Criteria — Investigational Laboratory Tests

Coding — Affected CPT/HCPCS/Proprietary Codes

Provider Actions — Prior Authorization, Documentation, and Denial Risk

Not Covered — Investigational Tests

Background and Scope

Definitions

Frequency Limits

Ordering Requirements