ApoE-e4 has a well-established connection to late-onset Alzheimer disease (AD) and is available clinically. Yet, there have been no analyses of payer coverage policies for ApoE. Our objective was to analyze private payer coverage policies for ApoE genetic testing, examine the rationales, and describe supporting evidence referenced by policies.
We searched for policies from the eight largest private payers (by member numbers) covering ApoE testing for late-onset AD. We implemented content analysis methods to evaluate policies for coverage decisions and rationales.
Seven payers had policies with positions on ApoE testing. Five explicitly state they do not cover ApoE and two apply generic preauthorization criteria. Rationales supporting coverage decisions include: reference to guidelines or national standards, inadequate data supporting testing, characterizing testing as investigational, or that testing would not alter patients’ clinical management.
Seven of the eight largest private payers’ coverage policies reflect standards that discourage ApoE testing due to a lack of clinical utility. As the field advances, ApoE testing may have an important clinical role, particularly considering that disease-modifying therapies are under evaluation by the US Food and Drug Administration. These types of field advancements may not be consistent with private payers’ policies and may cause payers to reevaluate existing coverage policies.
Subscribe to Journal
Get full journal access for 1 year
only $41.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
The data reported in this paper were collected through publicly available resources. Therefore, the authors did not deposit these data into another repository. Requests for tools or frameworks used in our analysis will be considered on a case-by-case basis.
2020 Alzheimer disease facts and figures. Alzheimer’s Dement. 16, 391–460 (2020). https://doi.org/10.1002/alz.12068.
Goldman, J. S. New approaches to genetic counseling and testing for Alzheimer disease and frontotemporal degeneration. Curr. Neurol. Neurosci. Rep. 12, 502–510 (2012).
Qian, J., Wolters, F. J. & Beiser, A. et al. APOE-related risk of mild cognitive impairment and dementia for prevention trials: an analysis of four cohorts. PLoS Med. 14, e1002254 (2017).
Belloy, M. E., Napolioni, V. & Greicius, M. D. A quarter century of APOE and Alzheimer disease: progress to date and the path forward. Neuron. 101, 820–838 (2019).
Goldman, J. S., Hahn, S. E. & Catania, J. W. et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med 13, 597–605 (2011).
Choosing Wisely. ACMG APOE genetic testing to predict Alzheimer disease. https://www.choosingwisely.org/clinician-lists/american-college-medical-genetics-genomics-apoe-genetic-testing-to-predict-alzheimer-disease/ (2020).
Schneider, L. A resurrection of aducanumab for Alzheimer disease. Lancet Neurol. 19, 111–112 (2020).
Statista. Largest U.S. health insurers by membership. https://www.statista.com/statistics/828436/largest-health-insurance-companies-in-us-by-membership/ (2020).
Hsieh, H.-F. & Shannon, S. E. Three approaches to qualitative content analysis. Qual. Health Res. 15, 1277–1288 (2005).
SAGE Ocean. NVIVO 12. https://ocean.sagepub.com/research-tools-database/nvivo (2020).
The Emerging Use By Commercial Payers Of Third-Party Lab Benefit Managers For Genetic Testing | Health Affairs. Accessed September 9, 2020. https://www.healthaffairs.org/do/10.1377/hblog20191021.563154/full/.
Jack, C. R., Albert, M. S. & Knopman, D. S. et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer disease. Alzheimer’s Dement. 7, 257–262 (2011).
Jack, C. R., Bennett, D. A. & Blennow, K. et al. NIA-AA Research Framework: toward a biological definition of Alzheimer disease. Alzheimer’s Dement. 14, 535–562 (2018).
Morris, J. C., Roe, C. M. & Xiong, C. et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol 67, 122–131 (2010).
Palmqvist, S., Janelidze, S. & Quiroz, Y. T. et al. Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA. 324, 772 (2020).
Foster, N. L., Mottola, K. & Hoffman, J. M. Coverage with evidence development: what to consider. JAMA Neurol. 71, 399–400 (2014).
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. Alzheimer disease drug development pipeline: 2020. Alzheimer’s Dement. https://doi.org/10.1002/trc2.12050 (2020).
Sperling, R. A., Jack, C. R. & Black, S. E. et al. Amyloid related imaging abnormalities (ARIA) in amyloid modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimer’s Dement. 7, 367–385 (2011).
US Food and Drug Administration.. FDA allows marketing of first direct-to-consumer tests that provide genetic risk information for certain conditions. https://www.fda.gov/news-events/press-announcements/fda-allows-marketing-first-direct-consumer-tests-provide-genetic-risk-information-certain-conditions (2020).
23andMe. About us. http://mediacenter.23andme.com/company/about-us/ (2020).
Healthcare IT News. Direct to consumer genetic testing set for big growth despite clinical and ethical challenges. https://www.healthcareitnews.com/news/direct-consumer-genetic-testing-set-big-growth-despite-clinical-and-ethical-challenges (2018).
Brothers, K. B. & Knapp, E. E. How should primary care physicians respond to direct-to-consumer genetic test results? AMA J. Ethics. 20, E812–E818 (2018).
Murphy, H. Don’t count on 23andMe to detect most breast cancer risks, study warns. New York Times. https://www.nytimes.com/2019/04/16/health/23andme-brca-gene-testing.html (2019).
Kilbride, M. K., Domchek, S. M. & Bradbury, A. R. How should patients and providers interpret the US Food and Drug Administration’s regulatory language for direct-to-consumer genetic tests? J. Clin. Oncol. 37, 2514–2517 (2019).
Kopits, I. M., Chen, C., Roberts, J. S., Uhlmann, W. & Green, R. C. Willingness to pay for genetic testing for Alzheimer disease: a measure of personal utility. Genet. Test. Mol. Biomarkers 15, 871–875 (2011).
Caselli, R. J., Langbaum, J. & Marchant, G. E. et al. Public perceptions of presymptomatic testing for Alzheimer disease. Mayo Clin. Proc. 89, 1389–1396 (2014).
Zick, C. D., Mathews, C., Roberts, J. S., Cook-Deegan, R., Pokorski, R. J. & Green, R. C. Genetic testing for Alzheimer disease and its impact on insurance purchasing behavior. Health Aff. (Millwood) 24, 483–490 (2005).
Taylor, D. H., Cook-Deegan, R. M., Hiraki, S., Roberts, J. S., Blazer, D. G. & Green, R. C. Genetic testing for Alzheimer’s and long-term care insurance. Health Aff. (Millwood) 29, 102–108 (2010).
Arias, J. J., Tyler, A. M., Oster, B. J. & Karlawish, J. The proactive patient: long-term care insurance discrimination risks of Alzheimer disease biomarkers. J. Law Med. Ethics 46, 485–498 (2018).
Trosman, J. R., Weldon, C. B., Slavotinek, A., Norton, M. E., Douglas, M. P. & Phillips, K. A. Perspectives of US private payers on insurance coverage for pediatric and prenatal exome sequencing: Results of a study from the Program in Prenatal and Pediatric Genomic Sequencing (P3EGS). Genet. Med. 22, 283–291 (2020).
Knopman, D. S., DeKosky, S. T., Cummings, J. L. et al. Practice parameter: diagnosis of dementia (an evidence-based review) - report of the Quality Standards Subcommittee of the American Academy of Neurology (reaffirmed 2004). Neurology. 56, 1143–1153 (2001).
Practice guidelines for the treatment of patients with Alzheimer’s disease and other dementias (2nd ed.). American Psychiatric Association Web site. (2006). http://www.psychiatryonline.com/content.aspx?aID=152608.
Genetic testing. Alzheimer’s Association Web site. (2008). http://www.alz.org/national/documents/topicsheet_genetictesting.pdf. Accessed 31 July 2014.
Screening for dementia: recommendations and rationale. United States Preventive Services Task Force Web site. (2003). http://www.uspreventiveservicestaskforce.org/3rduspstf/dementia/dementrr.htm. Accessed 31 July 2014.
Work reported in this publication was covered through funding from the National Cancer Institute (NCI)/National Human Genome Research Institute (U01 HG009599) and NCI (R01 CA221870). J.J.A. and A.M.T. have also been funded by the National Institute on Aging (NIA) (NIA-K01-AG057796).
Competing interests have been reviewed by the University of California–San Francisco. K.A.P. receives consulting income from Illumina, Inc. M.P.D. receives consulting income from Illumina, Inc. The other authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Arias, J.J., Tyler, A.M., Douglas, M.P. et al. Private payer coverage policies for ApoE-e4 genetic testing. Genet Med (2021). https://doi.org/10.1038/s41436-020-01042-4