General Approach to Genetic Testing
Genetic testing classified in one of the categories below may be considered medically necessary when all criteria are met for each category, as outlined in the Rationale section:
Genetic testing that does not meet the criteria for a specific category is considered investigational or not medically necessary, according to the standard definitions used for these terms (See Policy Guidelines section).
Genetic testing is considered not medically necessary when performed entirely for non-medical reasons (e.g., a general interest in genetic test results).
Note: This policy applies only if there is not a separate policy that outlines specific criteria for testing. If a separate policy does exist, then the criteria for medical necessity in that policy supersede the guidelines in this policy. (See Related Policies)
Experimental or Investigative Definition
Experimental or Investigational services include a treatment, procedure, equipment, drug, drug usage, medical device, or supply that meets one or more of the following criteria as determined by the Company:
Credible scientific evidence includes, but is not limited to, reports and articles published in authoritative peer- reviewed medical and scientific literature generally recognized by the relevant medical community, and assessments and coverage recommendations published by the Technology Evaluation Center (TEC).
Medical Necessity/Medically Necessary Definition
Those covered services and supplies that a Physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury, disease or its symptoms, and that are:
For these purposes, “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, Physician Specialty Society recommendations and the views of Physicians practicing in relevant clinical areas and any other relevant factors.
The fact that services were furnished, prescribed, or approved by a physician or other qualified provider does not in itself mean that services were medically necessary.
NOTE: A small number of member contracts may contain differing definitions of investigational or medically necessary services. The member booklet should be consulted for the definitions of investigational and/or medically necessary for that group.
Effective in 2013, if the specific analyte is listed in codes 81200-81355 or 81400-81408, that CPT code would be reported. If the specific analyte is not listed in the more specific CPT codes, unlisted code 81479 would be reported.
There are numerous commercially available genetic tests, including those used to guide intervention in symptomatic or asymptomatic people, to identify people at risk for future disorders, to predict the prognosis of diagnosed disease, and to predict treatment response. This concept policy offers a framework 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 provide assistance in evaluating the utility of genetic tests. In providing a framework for evaluating genetic tests, this policy will not attempt to determine the clinical utility of genetic testing for specific disorders. Rather, it provides guidelines that can be applied to a wide range of different tests.
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 medical policies for genetic testing in the reproductive setting (See Related Policies):
The following categories of genetic testing will be addressed in this policy:
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 mutation are typically unaffected. When associated with an autosomal dominant disorder, the person has one normal and one mutated copy of the gene and may be affected with the disorder, may be unaffected but at high risk of developing the disease later in life, or the carrier 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 mutations: Mutations that are present in the DNA of every cell of the body, present from the moment of conception. These include cells in the gonads (testes or ova) and could, therefore be passed on to offspring.
Somatic mutations: Variations that occur with the passage of time and are restricted to a specific cell or cells derived from it. If these variations are limited to cells that are not in the gonads, these variations will not be passed on to offspring.
Pharmacogenomics: Study of how a person’s genetic makeup affects the body’s response to drugs.
Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.
The test should be cleared or approved by the U.S. Food and Drug Administration or performed in a Clinical Laboratory Improvement Amendment-certified laboratory.
Peer-reviewed literature on the performance and indications for the test should be available. This evaluation of a genetic test focuses on 3 main principles: (1) analytic validity (technical accuracy of the test in detecting a mutation that is present or in excluding a mutation that is absent); (2) clinical validity, (diagnostic performance of the test [sensitivity, specificity, positive and negative predictive values] in detecting clinical disease); and (3) clinical utility ( i.e., how results of the diagnostic test will be used to change management of the patient and whether these changes in management lead to clinically important improvements in health outcomes.
Types of genetic tests addressed in this policy
Medical Necessity Criteria
Genetic testing is considered medically necessary for a genetic or heritable disorder when the following are met:
For ALL genetic testing, the condition being tested for must have either:
For the specific categories of testing, the following criteria must also be met:
Clinical Utility Criteria
For the following category, in which the benefit of testing is for another individual, the definition of medical necessity may not apply. When an individual is tested to benefit a family member, and there is no benefit for the individual being tested, eligibility for coverage is dependent on individual plan benefit language. Individual plans may differ as to whether benefit structure allows testing of an individual to benefit an unaffected family member.
Because of these concerns, the following criteria are considered to be criteria for clinical utility of testing and not for medical necessity.
Genetic counseling is primarily aimed at patients who are at risk for inherited disorders, and experts recommend formal genetic counseling in most cases when genetic testing for an inherited condition is considered. The interpretation of the results of genetic tests and the understanding of risk factors can be very difficult and complex. Therefore, genetic counseling will assist individuals in understanding the possible benefits and harms of genetic testing, including the possible impact of the information on the individual’s family. 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.
Limitations of Genetic Testing
The testing methods may not detect all of the mutations that may occur in a gene
Molecular diagnostics, code range
Molecular pathology procedure code range
Unlisted molecular pathology procedure
Appendix 1. Table for Categorizing Which Type of Testing Is Being Addressed in Separate Medical Policies
The following table will be used on individual genetic medical policies to indicate which categories are addressed in the policy, including both general genetic testing and reproductive genetic testing.
Appendix 2. APPROACH TO DETERMINING CLINICAL UTILITY FOR GENETIC TESTING
If direct evidence is available on the impact of testing on outcomes, this evidence takes precedence. Examples of direct evidence would be:
When direct evidence is not available, indirect evidence should be evaluated. Indirect evidence is evidence that addresses one or more components of a chain of evidence, but does not itself connect the intervention with the outcome.
An example of indirect evidence is the accuracy of the genetic test for diagnosing the clinical condition, ie, clinical sensitivity and specificity. If improved accuracy leads to improved diagnosis of the disorder, and if more accurate diagnosis leads to management changes that improve outcomes, then clinical utility has been established.
Many of these disorders are rare, and high-quality evidence on the efficacy of treatment for the disorder is often lacking. This is particularly true for aspects of management such as increased surveillance for complications, ancillary treatments (physical therapy, occupational therapy, etc.), and referrals to specialists. When evidence on outcomes is lacking, a consideration may be given as to whether these aspects of care are considered standard-of-care for that disorder, especially when they are part of guidelines by authoritative bodies.
There are a number of factors that influence the strength of indirect evidence that is needed to determine whether health outcomes are improved. None of these factors are by themselves determinative of whether genetic testing should be performed, but they may be important determinants of the potential clinical utility of testing . Some of these considerations are as follows:
Impact of genetic test on diagnosis
Impact of genetic test on management
Impact on Health Outcomes
Appendix Table 1. Factors influencing the strength of an indirect chain of evidence on clinical utility: Testing Categories 1a, 2a
Impact of genetic test on defining risk of disease
Impact on Health Outcomes
Appendix Table 2. Factors influencing the strength of indirect evidence for risk assessment testing: Testing Category 3
Impact of genetic test on prognosis
Impact of genetic test on management
Impact on Health Outcomes
Appendix Table 3. Factors influencing the strength of indirect evidence: Testing Categories 1b, 2b
Impact of genetic testing on assessing response to treatment
Impact of genetic test on pharmacologic management
Impact on Health Outcomes
Appendix Table 4. Factors influencing the strength of Indirect Evidence: genetic variants that alter response to treatment (Testing Categories 1c, 2c)
New Policy. Policy created with literature search through February 2013
Update Related Policies. Add 12.04.86 and 4.01.21.
Replace policy. Additional bullet added to clarify what is meant by environmental factors (“Genetic mutations that adversely affect response to exposures in the environment that are ordinarily tolerated, such as G6PD deficiency, genetic disorders of immune function, and aminoacidopathies.”).
Update Related Policies; new policy 12.04.97 added.
Update Related Policies. Add 12.04.99, 12.04.104, 12.04.105 and 12.04.106.
Update Related Policies. Add 12.04.102.
Update Related Policies. Change title to 12.04.75.
Update Related Policies; add new policies 12.04.103, 12.04.107, 12.04.108, 12.04.109, 12.04.110 and 12.04.111, all effective 12/9/13.
Update Related Policies. Change title to 12.04.504.
Update Related Policies. Change title to 12.04.48, add 12.04.113, and 12.04.114.
Update Related Policies. Add 2.04.115, 2.04.118, 2.04.119 and 12.04.509. Remove 12.04.82 as it was deleted.
Annual Review. Policy statements unchanged. No new literature has been identified for this concept policy update. Expanded framework for determining clinical utility has been added as an appendix for the four categories of diagnostic testing, risk assessment, prognostic testing, and pharmacogenomics.
Update Related Policies. Add 12.04.121.
Annual Review. Policy updated with new categories of genetic testing. No new references added. Medical necessity criteria revised for each new category of testing; for the category of testing an individual for the benefit of a family member, criteria are for clinical utility rather than medical necessity and this category has been moved back to the policy statement. Company definitions of medical necessity and investigative added.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).