Medical_Policy

Highmark Commercial Medical Policy - Pennsylvania

Medical Policy:	L-185-004
Topic:	APOE Variant Analysis for Alzheimer Disease
Section:	Laboratory
Effective Date:	November 13, 2017
Issue Date:	November 13, 2017
Last Reviewed:	June 2017

Alzheimer disease (AD) is characterized by adult-onset, progressive dementia with cerebral cortical atrophy and beta amyloid plaque formation.

There are three common versions of the (Apolipoprotein E) APOE gene - e2, e3, and e4. The e4 variant is significantly associated with AD. People with AD, and especially late-onset familial AD, are more likely to have one or two copies of APOE e4. APOE e4 appears to cause susceptibility to AD, but the reason is unclear. Clinical testing is available to determine which two APOE gene versions a person has inherited.

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.

APOE variant analysis for AD is considered experimental/investigational (E/I) and therefore non-covered.

E/I molecular and genomic (MolGen) tests refer to assays involving chromosomes, DNA, RNA, or gene products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition.
In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.

Procedure Codes

81401, S3852

Professional Statements and Societal Positions

Guidelines and Evidence

Diagnostic Testing:
- European Federation of Neurological Societies (2010): “The ApoE e4 allele is the only genetic factor consistently implicated in late-onset AD, but it is neither necessary nor sufficient for development of the disease. Hence, there is no evidence to suggest ApoE testing is useful in a diagnostic setting.”
- American College of Medical Genetics and The National Society of Genetic Counselors (2011)
  - "Genetic testing for susceptibility loci (e.g., APOE is not clinically recommended due to limited clinical utility and poor predictive value."
- National Institute of Aging/Alzheimer's Association Working Group (1997):
  - "Insofar as patients with AD are more likely to have an APOE-e4 allele than are patients with other forms of dementia or individuals without dementia, physicians may choose to use APOE genotyping as an adjunct to other diagnostic tests for AD."
  - "Since genotyping cannot provide certainty about the presence or absence of AD, it should not be used as the sole diagnostic test."
Predictive Testing:
- American College of Medical Genetics and The National Society of Genetic Counselors (2011): “Because the ε4 allele is neither necessary nor sufficient to cause AD, there have been numerous consensus statements and articles that have recommended against using APOE genotyping for predicting AD risk.”
- National Institute of Aging/Alzheimer's Association Working Group (1997): "The use of APOE genotyping to predict future risk of AD in symptom-free individuals is not recommended at this time."

Place of Service: Outpatient

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

APOE variant analysis for AD 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 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.

Links

Link to References

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.

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