Highmark Commercial Medical Policy - Pennsylvania

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Medical Policy: L-114-005
Topic: Pharmacogenomic Testing for Drug Toxicity and Response
Section: Laboratory
Effective Date: July 1, 2018
Issue Date: July 2, 2018
Last Reviewed: March 2018

For the purposes of this policy, pharmacogenomic tests are performed to assess a person’s response to therapy or risk for toxicity from drug treatment. Testing may be performed prior to treatment, in order to determine if the individual has genetic differences that could affect drug response and/or increase the risk for adverse drug reactions. Testing may also be performed during treatment, to assess whether an individual is having an adequate response or to investigate the cause of an unusual or adverse reaction.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

Pharmacogenomic tests may be considered medically necessary when ALL of the following conditions are met:

  • The individual is currently taking or considering treatment with a drug potentially affected by a known mutation that can be detected by a corresponding test ; and
  • Technical and clinical validity: The test must be accurate, sensitive, and specific, based on sufficient, quality scientific evidence to support the claims of the test; and
  • Clinical utility: Healthcare providers can use the test results to guide changes in drug therapy management that will improve patient outcomes; and
  • Reasonable use: The usefulness of the test is not significantly offset by negative factors, such as expense, clinical risk, or social, or ethical challenges.

Companion Diagnostic Testing may be considered medically necessary when ALL of the following conditions are met:

  • Testing is being performed in a CLIA-certified laboratory; and
  • Testing is NOT being performed as part of a panel of genes; and
  • Testing of the requested gene has not previously been performed; and
  • A medication’s FDA label requires results from the genetic test to effectively or safely use the therapy in question; and
  • Healthcare providers can use the test results to directly impact medical care for the individual; or
  • The member meets all criteria in a test-specific guideline, if available


  • Testing may be considered medically necessary only for the number of genes or tests necessary to establish drug response. When available and cost-efficient, a tiered approach to testing, with reflex to more detailed testing and/or different genes, is recommended.
  • For pharmacogenomic tests that look for changes in germline DNA (i.e., not tumor DNA or viral DNA), testing will be allowed once per lifetime per gene. Exceptions may be considered medically necessary if technical advances in testing demonstrate significant advantages that would support a medical need to retest.


The following pharmacogenomic tests are considered experimental/investigational and therefore non-covered due to lack of scientific-based evidence, professional guidelines and/or the FDA, or their use in medical management is deemed to be still evolving.

This list is not intended to be all inclusive.

  • 5HT2C (Serotonin Receptor) gene variants
  • Ankyrin G gene variants
  • COMT (Catechol Methyl Transferase) gene variants
  • Catechol-O-Methyltransferase (COMT) Genotype from Mayo Clinic
  • CYP450 gene variants (including, but not limited to CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4, CYP3A5) for psychotherapeutic, cardiovascular, or general drug response
  • Cytochrome P450 1A2 Genotype from Mayo Clinic
  • CYP2C19 testing for the management of H. pylori
  • DRD2 (Dopamine Receptor) gene variants
  • Focused Pharmacogenomics Panel from Mayo Clinic
  • IFNL3 rs12979860 gene variant
  • KIF6 gene variants
  • MTHFR gene variants
  • NAT2 gene variants
  • OPRM1 gene variants
  • Serotonin Receptor Genotype (HTR2A and HTR2C) from Mayo Clinic
  • SLC6A4 (5-HTTLPR) serotonin transporter variants
  • Thiopurine Methyltransferase (TPMT) and Nudix Hydrolase (NUDT15) Genotyping
  • from Mayo Clinic
  • Warfarin Response Genotype from Mayo Clinic
Procedure Codes
81283, 0029U, 0030U, 0031U, 0032U, 0033U, 0034U

Place of Service: Outpatient

Experimental/Investigational (E/I) services are not covered regardless of place of service.

Pharmacogenomic testing for drug toxicity and response is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.


Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:
  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
    • Qualified sign language interpreters
    • Written information in other formats (large print, audio, accessible electronic formats, other formats)
  • Provides free language services to people whose primary language is not English, such as:
    • Qualified interpreters
    • Information written in other languages
If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

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