Cost-effectiveness analysis (CEA) of next generation sequencing (NGS) in etiologic evaluations for prelingual hearing loss. M. E. Nunes1, N. T. Manzano1, J. L. Natoli2, K. A. Wendt3 1) Dept Genetics/Pediatrics, Kaiser Permanente, San Diego, CA; 2) Department of Clinical Analysis Technology Assessment and Guidelines Unit Kaiser Permanente, Pasadena, CA; 3) Medical Genetics and Genomics Laboratories, Kaiser Permanente, Los Angeles, CA.

   We used cost-effectiveness analysis (CEA) to examine the estimated cost, diagnostic impact, and efficiency afforded by incorporating Next Generation Sequencing (NGS) into hearing loss evaluations performed during the first year of life. Newborn hearing screen (NBHS) identifies hearing loss in 1.2 per 1,000 infants. Half of the congenital cases are ultimately found to be genetic, of which 30% are syndromic, requiring additional diagnostic evaluation. Establishing etiology may identify comorbidity, determine management and prognosis, and facilitate genetic counseling. A multidisciplinary systematic approach includes appropriate genetic testing, until recently limited within our managed care institution to Connexin 26 and 30 (Cx 26/30) genes and locus specific testing. Using the evaluation strategy proposed by the British Association of Audiological Physicians (2007), we evaluated the theoretical impact on diagnosis and cost of three genetic testing schemes: 1) Cx26/30, 2) Cx 26/30 as first tier with reflex to NGS if negative, and 3) NGS only. Genetic testing would occur after confirmation of congenital hearing loss and clinical evaluation by an Otolaryngologist, prior to additional work-up for genetic and non-genetic etiology. The cost of NGS was $1500 per sample, assumed to incorporate > 50 loci for non-syndromic and syndromic hearing loss. We calculated total, average, and marginal cost per diagnosis established. Cytomegalovirus (CMV) testing ($286,970) and Ophthalmology evaluation ($443,182) had the largest marginal cost per diagnosis made, Connexin 26/30 gene testing ($3494) and Otolaryngology clinical evaluation ($5720) the lowest. Scheme 1 identified a diagnosis in 33% by 1 year of age, with average cost per diagnosis $6168. Scheme 2 identified 41%, with average cost $7456. Scheme 3 likewise identified 41%, but became the most effective method with average cost $6679 and NGS marginal cost per diagnosis $5249. Although the individual cost of DNA testing for Connexin 26/30 is considerably less than NGS, introducing NGS early in the evaluation of congenital hearing loss reduced both diagnoses made by clinical evaluations and need for imaging studies, resulting in cost saving. This analysis suggests that NGS could successfully be incorporated early in hearing loss evaluations with significant savings in time and money. Similar CEA are possible to justify the expense of NGS platforms in other medical conditions with well established diagnostic pathways.

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