Yield of whole exome sequencing in undiagnosed patients facing insurance coverage barriers to genetic testing

Chloe M Reuter; Jennefer N Kohler; Devon Bonner; Diane Zastrow; Liliana Fernandez; Annika Dries; Shruti Marwaha; Jean Davidson; Elly Brokamp; Matthew Herzog; Joyce Hong; Ellen Macnamara; Jill A Rosenfeld; Kelly Schoch; Rebecca Spillmann; Undiagnosed Diseases Network; Joseph Loscalzo; Joel Krier; Joan Stoler; David Sweetser; Christina G S Palmer; John A Phillips; Vandana Shashi; David A Adams; Yaping Yang; Euan A Ashley; Paul G Fisher; John J Mulvihill; Jonathan A Bernstein; Matthew T Wheeler

doi:10.1002/jgc4.1161

Yield of whole exome sequencing in undiagnosed patients facing insurance coverage barriers to genetic testing

J Genet Couns. 2019 Dec;28(6):1107-1118. doi: 10.1002/jgc4.1161. Epub 2019 Sep 3.

Authors

Chloe M Reuter^{1

2}, Jennefer N Kohler^{1

2}, Devon Bonner^{1

2}, Diane Zastrow^{1

2}, Liliana Fernandez^{1

2}, Annika Dries^{1

2}, Shruti Marwaha^{1

2}, Jean Davidson^{1

2}, Elly Brokamp³, Matthew Herzog⁴, Joyce Hong⁵, Ellen Macnamara⁶, Jill A Rosenfeld⁷, Kelly Schoch⁸, Rebecca Spillmann⁸; Undiagnosed Diseases Network; Joseph Loscalzo⁵, Joel Krier⁵, Joan Stoler⁹, David Sweetser¹⁰, Christina G S Palmer^{4

11

12}, John A Phillips³, Vandana Shashi⁸, David A Adams⁶, Yaping Yang⁷, Euan A Ashley^{1

2

13}, Paul G Fisher^{1

14

15}, John J Mulvihill¹⁶, Jonathan A Bernstein^{1

15}, Matthew T Wheeler^{1

2}

Affiliations

¹ Center for Undiagnosed Diseases, Stanford University School of Medicine, Stanford, CA.
² Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA.
³ Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
⁴ Department of Human Genetics, University of California Los Angeles, Los Angeles, CA.
⁵ Department of Medicine, Brigham and Women's Hospital, Boston, MA.
⁶ Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.
⁷ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.
⁸ Department of Pediatrics, Duke University Medical Center, Durham, NC.
⁹ Division of Genetics, Boston Children's Hospital, Boston, MA.
¹⁰ Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, Boston, MA.
¹¹ Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA.
¹² Institute for Society & Genetics, University of California Los Angeles, Los Angeles, CA.
¹³ Department of Genetics, Stanford University School of Medicine, Stanford, CA.
¹⁴ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA.
¹⁵ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
¹⁶ Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD.

Abstract

Background: Despite growing evidence of diagnostic yield and clinical utility of whole exome sequencing (WES) in patients with undiagnosed diseases, there remain significant cost and reimbursement barriers limiting access to such testing. The diagnostic yield and resulting clinical actions of WES for patients who previously faced insurance coverage barriers have not yet been explored.

Methods: We performed a retrospective descriptive analysis of clinical WES outcomes for patients facing insurance coverage barriers prior to clinical WES and who subsequently enrolled in the Undiagnosed Diseases Network (UDN). Clinical WES was completed as a result of participation in the UDN. Payer type, molecular diagnostic yield, and resulting clinical actions were evaluated.

Results: Sixty-six patients in the UDN faced insurance coverage barriers to WES at the time of enrollment (67% public payer, 26% private payer). Forty-two of 66 (64%) received insurance denial for clinician-ordered WES, 19/66 (29%) had health insurance through a payer known not to cover WES, and 5/66 (8%) had previous payer denial of other genetic tests. Clinical WES results yielded a molecular diagnosis in 23 of 66 patients (35% [78% pediatric, 65% neurologic indication]). Molecular diagnosis resulted in clinical actions in 14 of 23 patients (61%).

Conclusions: These data demonstrate that a substantial proportion of patients who encountered insurance coverage barriers to WES had a clinically actionable molecular diagnosis, supporting the notion that WES has value as a covered benefit for patients who remain undiagnosed despite objective clinical findings.

Keywords: diagnostic yield; exome sequencing; insurance coverage; rare diseases; reimbursement; undiagnosed diseases; access; genetic testing; policy; public health.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Child
Child, Preschool
Exome Sequencing*
Female
Genetic Testing / methods
Humans
Insurance Coverage*
Male
Retrospective Studies
Undiagnosed Diseases / genetics*
United States

Abstract

Publication types

MeSH terms

Grants and funding