Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Pharmacogenetic Testing to Determine Drug Sensitivity
Policy #:MA06.008b

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

MEDICALLY NECESSARY

Certain pharmacogenetic tests to determine drug sensitivity are considered medically necessary and, therefore, covered when the medical necessity criteria and the technical requirements listed in the associated attachments to this medical policy are met.

EXPERIMENTAL/INVESTIGATIONAL

Certain pharmacogenetic tests to determine drug sensitivity are considered experimental/investigational and, therefore, not covered. Refer to the associated attachments of this medical policy for more detail.

The individual attachments contain more comprehensive information, medical necessity criteria, and specific procedure codes on each topic.
  • Attachment A: Cytochrome p450 Genotyping for Assessment of Individuals Prior to Initiation of Clopidogrel Bisulfate (Plavix®)
  • Attachment B: Pharmacogenomic Testing (CYP2C9 or VKORC1 alleles) for Predicting Warfarin Response
  • Attachment C: Pharmacogenetic Testing to Determine Cytochrome p450 (CYP2C19) Genetic Polymorphisms for Treatment/Management of Helicobacter Pylori (H. pylori)Infection
  • Attachment D: Pharmacogenetic Testing to Determine Cytochrome p450 (CYP2D6) Genetic Polymorphisms for Management of Tamoxifen Treatment for Women with, or at High Risk for, Breast Cancer
  • Attachment E: KRAS and BRAF Mutation Analysis in Metastatic Colorectal Cancer Prior to Use of Cetuximab (Erbitux®) and Pantiumumab (Vectibix®)
  • Attachment F: Pharmacogenetic Testing for Predicting Cardiovascular Risk and/or Effectiveness of Statin Therapy by KIF6 Genotyping
  • Attachment G: KRAS Mutation Analysis to Predict Treatment Response to Erlotinib (Tarceva®) in Non-Small-Cell- Lung Cancer (NSCLC)
  • Attachment H: Epidermal Growth Factor (EGFR) Mutation Analysis for Individuals with Non-Small-Cell Lung Cancer (NSCLC)
  • Attachment I: Pharmacogenetic Testing for the BRAF (V600E) Mutation in Tumor Tissue for Select Individuals for Treatment with Vemurafenib (Zelboraf®)
  • Attachment J: BCR-ABL Testing for Monitoring of Individuals with Chronic Myelogenous Leukemia or Acute Myelogenous Leukemia, Who Are Receiving Imatinib Mesylate (Gleevec®) Therapy

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Policy Guidelines

This policy is consistent with Medicare's coverage determination. The Company's reimbursement methodology may differ from Medicare.

When there are no Medicare coverage criteria addressing pharmacogenetic services listed in this policy, the Company policy is applicable.

BENEFIT APPLICATION

MEDICALLY NECESSARY
Subject to the terms and conditions of the applicable Evidence of Coverage, certain pharmacogenetic testing to determine drug sensitivity is covered under the medical benefits of the Company's Medicare Advantage products when the medical necessity criteria and the technical requirements listed in this medical policy are met.

EXPERIMENTAL/INVESTIGATIONAL
Subject to the terms and conditions of the applicable Evidence of Coverage, certain pharmacogenetic testing to determine drug sensitivity listed in this policy is not eligible for payment under the medical benefits of the Company's Medicare Advantage products because the service is considered experimental/investigational and, therefore, not covered.

Description

Pharmacogenomics describes the relationship between variations in the human genome (ie, differences in DNA sequence, copy number, or transcriptional perturbations) and individual variations in response to drug therapy, including adverse effects of drug therapy.

According to the National Center for Biologic Information (NCBI), pharmacogenetics and pharmacogenomics are defined as follows:
  • Pharmacogenomics refers to the general study of all of the many different genes that determine drug behavior.
  • Pharmacogenetics refers to the study of inherited differences (variation) in drug metabolism and response.

While there is a distinction between the two terms, they are often used interchangeably in the scientific community.

The goal of pharmacogenetic research is the development of personalized medicine. Personalized medicine takes into account an individual's characteristics, such as genetic makeup and other specific biomarkers in order to provide patient-specific care. Once specific genetic information is known that allows for the ability to detect key genetic variations in individuals, it will permit the health care provider to determine the most effective treatment response and/or avoid severe adverse reactions. Currently, the optimal drug doses are defined by averages from data in clinical trials with large populations. If an individual can be identified who may have a high propensity for a severe reaction to a particular drug, this personalized approach can allow for the consideration of an alternate dosage of a drug or a completely alternative treatment. This proactive treatment approach would help to avoid extended monitoring and the intensive medical support required for severe toxicity reactions. Moreover, this new approach to individualized therapy can assist in the early selection of the most appropriate drug or drug dose where it is known that the response to the specific agent is variable depending on the person's genetic architecture.

The Centers for Disease Control and Prevention (CDC) Office of Public Health Genomics helped to establish and support the ACCE Model Project, which has become the standard for evaluating scientific data on new genetic tests. The ACCE Model System* for Collecting, Analyzing and Disseminating Information on Genetic Tests provides an evaluation framework that is applicable to a variety of genetic tests. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) used the ACCE framework and established this process as a way of evaluating an evidence-based method for assessing genetic tests and other types of genomic technology as it has transitioned from the research arena to the practice arena. The ACCE evaluation framework examines:
  • Analytical validity: Measures the specific genotypic test performance characteristics and whether the test accurately and reliably detects the gene marker(s) of interest. This refers to how well a test performs in the laboratory and how well the test measures the property or characteristic it is intended to measure. If the test does what its makers claim, it must produce the same results repeatedly and in different laboratories given the same set of procedures.
  • Clinical validity: Refers to the associations of the test result(s) with patient outcomes of interest; may be expressed as clinical sensitivity, specificity, and predictive value for the outcome. Evidence is usually retrospective. This component refers to the accuracy with which a test predicts the presence or absence of a clinical condition or predisposition. Initially, the test has to be conducted on individuals who are known to have the condition (as well as those who do not) to determine its success rate.
  • Clinical utility: Determines whether the use of genetic testing to modify management decisions improves patient outcomes. Best evidence is prospective, from randomized clinical trials of standard management procedures vs. genetic test-directed management. Evidence may also be derived by using banked samples from already completed clinical trials or by constructing an indirect chain of evidence linking test result to clinical outcome. This refers to the usefulness of the test and the value of information to the person being tested. If a test has utility, it means that the results, positive or negative, provide information that is of value to the person being tested because he or she can use that information to seek an effective treatment or preventive strategy. Even if no interventions are available to treat or prevent disease, there may be benefits associated with knowledge of a result.
  • Ethical, Legal, and Social Implications: Determines what, if any, ethical, legal, or social implications may arise from the use of this test and its results.

*From: Haddow JE, Palomaki GE. ACCE: A Model Process for Evaluating Data on Emerging Genetic Tests. In: Human Genome Epidemiology: A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease. Khoury M, Little J, Burke W (eds.), Oxford University Press, pp. 217-233, 2003.
References

Centers for Disease Control and Prevention. Office of Public Health Genomics. Evaluation of Genomic Testing. ACCE Model for Evaluating Genetic Tests. [Office of Public Health Genomics Web Site] January 3, 2011. Available at: http://www.cdc.gov/genomics/gtesting/ACCE/index.htm. Accessed July 31, 2013.

Centers for Disease Control and Prevention. Office of Public Health Genomics. Public Health Genomics. Genetic Testing. [Office of Public Health Genomics Web Site]. December 14, 2010. Available at:.http://www.cdc.gov/genomics/gtesting/index.htm Accessed July 31, 2013.

Centers for Disease Control and Prevention. Public Health Genomics. Genomic Testing. ACCE Model for Evaluating Genetic Testing. Available at: http://www.cdc.gov/genomics/gtesting/ACCE/index.htm. Accessed July 31, 2013.

Centers for Disease Control and Prevention. Public Helath Genomics. Genomic Testing. ACCE Model list of 44 targeted questions aimed at a comprehensive review of genetic testing. [Office of Public Helath Genomic Web Site]. December 12, 2010. Available at: http://www.cdc.gov/genomics/gtesting/ACCE/acce_proj.htm#wheel. Accessed July 31, 2013.

Center for Genetics Education. Pharmacogenetics/Pharmacogenomics. Fact Sheet 25. Available at: http://www.genetics.com.au/pdf/factsheets/fs25.pdf. Accessed July 31, 2013.

Genomics.Energy.gov. Human Genomic Project Information. Available at:http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml. Accessed July 31, 2013.

Gudgeon JM, McClain MR, Palomaki GE, Williams MS. Rapid ACCE: experience with a rapid and structured approach for evaluating gene-based testing. Genet Med. 2007;9:473-478.

Guttmacher AE, Feero WG, Collins FS. The genome gets personal--almost. JAMA. 2008;299(11):1351-1352.

Mayo Clinic. Pharmacogenomics: When drug treatment becomes personalized medicine. [June 27, 2008]. Available at:http://www.mayoclinic.com/health/personalized-medicine/CA00078. Accessed July 31, 2013.

National Center for Biologic Information. A Science Primer: Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources. One Size Does Not Fit All: The Promise of Pharmacogenetics. [National Center for Biologic Information Web Site]. Last Revised 3/31/2004. Available at: http://www.ncbi.nlm.nih.gov/About/primer/pharm.html. Accessed July 31, 2013.


Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

PLEASE REVIEW THE SPECIFIC INDIVIDUAL ATTACHMENTS FOR CODING INFORMATION ON EACH TOPIC LISTED IN THIS MEDICAL POLICY.


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

N/A


HCPCS Level II Code Number(s)



PLEASE REVIEW THE SPECIFIC INDIVIDUAL ATTACHMENTS FOR CODING INFORMATION ON EACH TOPIC LISTED IN THIS MEDICAL POLICY.


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Cytochrome p450 Genotyping for Assessment of Individuals Prior to Initiation of Clopidogrel Bisulfate (Plavix®)

Attachment B: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Pharmacogenomic testing (CYP2C9 or VKORC1 alleles) for predicting warfarin response

Attachment C: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Pharmacogenetic Testing to Determine Cytochrome p450 (CYP2C19) Genetic Polymorphisms for Treatment/Management of Helicobacter Pylori (H. pylori) Infection

Attachment D: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Pharmacogenetic Testing to Determine Cytochrome p450 (CYP2D6) Genetic Polymorphisms for Management of Tamoxifen Treatment for Women with, or at High Risk for Breast Cancer

Attachment E: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: KRAS and BRAF Mutation Analysis in Metastatic Colorectal Cancer Prior to Use of Cetuximab (Erbitux®) and Pantiumumab (Vectibix®)

Attachment F: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Pharmacogenetic Testing for Predicting Cardiovascular Risk and/or Effectiveness of Statin Therapy by KIF6 Genotyping

Attachment G: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: KRAS mutation analylsis to predict treatment response to erlotinib (Tarceva®) in non-small cell lung cancer (NSCLC)

Attachment H: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Epidermal Growth Factor (EGFR) Mutation Analysis for individuals with non-small cell lung cancer

Attachment I: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: Pharmacogenetic testing for the BRAF (V600E) mutation in tumor tissue for select individuals for treatment with vemurafenib (Zelboraf®)

Attachment J: Pharmacogenetic Testing to Determine Drug Sensitivity
Description: BCR-ABL Testing for Monitoring of Individuals with Chronic Myelogenous Leukemia or Acute Myelogenous Leukemia, who are Receiving Imatinib MesylateTherapy







Policy History

Revisions for MA06.008b
10/09/2019This policy has been reissued in accordance with the Company's annual review process.
11/21/2018This policy has been reissued in accordance with the Company's annual review process.
11/22/2017This policy has been reissued in accordance with the Company's annual review process.
07/01/2016This version of the policy will become effective 07/01/2016.

The notable difference in the updated version of this policy from that of the previous version is fixing of language in the benefit application section of Attachment G.

Revisions for MA06.008a
01/01/2016This policy has been identified for the CPT code update, effective 01/01/2016.

The narratives for the following CPT codes have been revised in the applicable attachments of this policy:

81210, 81275, 81355, 81403

Revisions for MA06.008
01/01/2015This is a new policy.





Version Effective Date: 07/01/2016
Version Issued Date: 07/01/2016
Version Reissued Date: 10/10/2019