General Approach to Genetic Testing

POLICY NUMBER

A.2.04.91

DESCRIPTION

Commercially available genetic tests can perform a host of functions, such as providing a guided intervention in symptomatic or asymptomatic people, identifying people at risk for future disorders, predicting the prognosis of a diagnosed disease, and predicting the appropriate treatment response. The conceptual framework offers an outline for evaluating the utility of genetic tests, by classifying the types of genetic tests into clinically relevant categories and developing criteria that can be used for evaluating tests in each category.

The purpose of this policy is to assist in evaluating the utility of genetic tests. In providing a framework for evaluating genetic tests, this policy will not determine the clinical utility of genetic testing for specific disorders. Rather, it provides guidelines that can be applied to a wide range of tests. Refer to the  Genetic Testing  medical policy for coverage criteria for specific genetic tests.

This policy applies only if there is not a separate medical policy that outlines specific criteria for testing. If a separate policy exists, then the criteria for medical necessity in that policy supersedes the guidelines in this policy.

This policy does not include cytogenetic testing (karyotyping), biochemical testing, or molecular testing for infectious disease. This policy does not address reproductive genetic testing. There are separate policies for genetic testing in the reproductive setting, addressing, eg,  Carrier Screening for Genetic Diseases  and Invasive Prenatal (Fetal) Diagnostic Testing . The following categories of genetic testing are addressed in this policy– 

1. Testing of an affected (symptomatic) individual's germline to benefit the individual.

a. Diagnostic - To confirm or exclude genetic or heritable variants in a symptomatic person. This refers to a molecular diagnosis supported by the presence of a known pathologic variant. For genetic testing, a symptomatic person is defined as an individual with a clinical phenotype correlated with a known pathologic variant.

b. Prognostic - To determine or refine estimates of disease natural history or recurrence in patients already diagnosed with disease in order to predict natural disease course (e.g., aggressiveness, recurrence, risk of death). This type of testing may use gene expression of affected tissue to predict the course of disease (e.g., testing breast cancer tissue with Oncotype DX).

c. Therapeutic - To determine that a particular therapeutic intervention is effective (or ineffective) for an individual. To determine the probability of favorable or adverse response to medications. To detect genetic variants that alter risk of treatment response, adverse events, drug metabolism, drug effectiveness, etc. (eg, cytochrome P450 testing). To detect genetic variants that adversely affect response to exposures in the environment that are ordinarily tolerated (eg, G6PD deficiency, genetic disorders of immune function, aminoacidopathies).

2. Testing cancer cells of an affected individual to benefit the individual.

a. Diagnostic - To determine the origin of a cancer or to determine a clinically relevant subgroup into which a cancer is classified.

b. Prognostic - To determine the risk of progression, recurrence, or mortality for a cancer that is already diagnosed.

c. Therapeutic - To determine the likelihood that a patient will respond to a targeted cancer therapy that is based on the presence or absence of a specific variant.

3. Testing an asymptomatic individual to determine future risk of disease. To detect genetic variants associated with disorders that appear after birth, usually later in life. Such testing is intended for individuals with a family history of a genetic disorder, but who themselves have no features of the disorder, at the time of testing, in order to determine their risk for developing the disorder.

4. Testing of an affected individual's germline to benefit family member(s). To focus and direct family testing of asymptomatic relatives, by testing an individual with known disease but in whom the presence or absence of a pathologic variant has not been determined.

Genetic testing category 5 (Reproductive testing) is not addressed in this policy.

Definitions

Genetic Testing: Genetic testing involves the analysis of chromosomes, DNA (deoxyribonucleic acid), RNA (ribonucleic acid), genes, or gene products to detect inherited (germline) or non-inherited (somatic) genetic variants related to disease or health.

Carrier Testing: A carrier of a genetic disorder has one abnormal allele for a disorder. When associated with an autosomal recessive or X-linked disorder, carriers of the causative variant are typically unaffected. When associated with an autosomal dominant disorder, the person has one normal and one mutated copy of the gene; such a person may be affected with the disorder, may be unaffected but at high risk of developing the disease later in life, or may remain unaffected because of the sex-limited nature of the disease.

Carrier testing may be offered to people: A) who have family members with a genetic condition; B) who have family members who are identified carriers; and C) who are members of ethnic or racial groups known to have a higher carrier rate for a particular condition.

Germline Variants: Germline variants are present in the DNA of every cell of the body, from the moment of conception. They include cells in the gonads (testes or ova) and could, therefore, be passed on to offspring.

Somatic Variants: Somatic variations occur with the passage of time and are restricted to a specific cell or cells derived from it. If these variants are limited to cells that are not in the gonads, they will not be passed on to offspring.

Pharmacogenomics: The study of how a person's genetic makeup affects his or her body’s response to drugs.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Most genetic tests are lab tests available under the auspices of the CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.

POLICY

Genetic testing is classified into one of the four categories below. To be considered medically necessary, all criteria for the specific category must be met.   

 For ALL genetic testing, the condition being tested for must have either:

• Reduced life expectancy OR

• At least moderate-to-severe morbidity

Genetic testing is considered not medically necessary when:

1. Testing does not meet the criteria for a specific category listed above.

2. Testing is performed for screening purposes where the member does not display clinical features or is not at direct risk of inheriting the mutation in question.  

3. Testing is not considered standard of care, such as the clinical diagnosis can be made without the use of a genetic test.

4. Testing is not clinically appropriate for the patient’s condition, for example, when it would not change diagnosis and/or management. Other situations where testing is not clinically appropriate include, but are not limited to:

   • testing performed entirely for non-medical (e.g., social) reasons

   • testing not expected to provide a definitive diagnosis that would obviate the need for further testing.

5. Testing is performed primarily for the convenience of the patient, physician or other health care provider.

6. Testing would result in outcomes that are equivalent to outcomes using an alternative strategy, and the genetic test is more costly.

Genetic testing is considered investigational when there is insufficient evidence to determine whether the technology improves health outcomes.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

For the following category of testing, the benefit of testing is for a family member rather than the individual being tested. In this category, the criteria developed are for clinical utility.

Genetics Nomenclature Update

The Human Genome Variation Society nomenclature is used to report information on variants found in DNA and serves as an international standard in DNA diagnostics. It is being implemented for genetic testing medical evidence review updates starting in 2017 (see Table 1). The Society’s nomenclature is recommended by the Human Variome Project, the HUman Genome Organization, and by the Human Genome Variation Society itself.

The American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines for interpretation of sequence variants represent expert opinion from both organizations, in addition to the College of American Pathologists. These recommendations primarily apply to genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. Table 2 shows the recommended standard terminology—“pathogenic,” “likely pathogenic,” “uncertain significance,” “likely benign,” and “benign”—to describe variants identified that cause Mendelian disorders.

Table 1. Nomenclature to Report on Variants Found in DNA

Table 2. ACMG-AMP Standards and Guidelines for Variant Classification

Genetic Counseling

Experts recommend formal genetic counseling for patients who are at risk for inherited disorders and who wish to undergo genetic testing. Interpreting the results of genetic tests and understanding risk factors can be difficult for some patients; genetic counseling helps individuals understand the impact of genetic testing, including the possible effects the test results could have on the individual or their family members.It should be noted that genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

07/18/2013: New policy added. Approved by Medical Policy Advisory Committee.

09/15/2014: Policy reviewed; no changes.

06/09/2016: Policy number added. Policy Guidelines updated to add medically necessary and investigative definitions.

08/11/2016: Policy description and policy statements updated with new categories of genetic testing. Added policy statement that for all genetic testing, the condition being tested for must have either reduced life expectancy or at least moderate-to-severe morbidity. Medically necessary criteria revised for each new category of testing. Category 4, testing an individual for the benefit of a family member, is listed in the Policy Guidelines section as it is for clinical utility rather than medical necessity. Added genetic counseling information.

01/18/2018: Policy description and statements updated to change "mutation" to "variant." Policy Guidelines updated regarding genetics nomenclature and genetic counseling.

SOURCE(S)

 Blue Cross and Blue Shield Association Policy # 2.04.91

CODE REFERENCE

Refer to the  Genetic Testing  medical policy for coverage criteria of specific procedures.