Cost and Clinical Utility of WES and WGS in pediatric patients with suspected genetic disease

Payer coverage for Exome Sequencing (ES) is becoming commonplace (albeit in some cases with prior authorization restrictions), coverage for Genome Sequencing (GS) is rare, with most payers considering it as investigational and not medically necessary. Previous studies had identified several concerns and challenges from the payer perspective. The objective of this study is to conduct a targeted literature review of the evidence describing the cost and clinical utility of GS and ES compared to standard of care (SoC) testing in children [&le;]18 years with suspected genetic disease. We conducted a systematic literature review to identify evidence for cost, diagnostic utility and clinical utility between SoC, ES, and GS in children (0-18 years) with suspected genetic diseases. We also identified list prices for individual tests from Concert Genetics. Descriptive analyses were conducted for cost and comparative effectiveness data. We identified five studies on costs of ES and GS, as well as data from concert genetics, and 62 studies of comparative effectiveness of GS or ES in pediatric patients <18 yrs. with suspected genetic disease. We identified 2 reviews/systematic literature review, one cost savings, one micro-costing, and one cost-effectiveness analysis, in addition to the list prices from Concert Genetics which support the range of costs in the articles. List prices ranged from an average of $2264 (small panel) to $7245 for a rapid ES trio. Nearly half the studies (28/63; 44%) only reported diagnostic yield, and 18 studies with NICU/PICU patients and 18 studies of outpatients that reported a change in management. The change in management was very heterogeneous ranging from 24% to 83% depending on the patients suspected disorder and test type (e.g., rapid GS, rapid ES, GS). We were unable to determine if any of the GS test types (ultra-rapid GS or rapid GS or GS, range 24% - 83%) provided a greater change in clinical management rate than the ES test types (rapid ES or ES, range 35% - 83%). There is limited evidence of GS over ES in the ability to effect change in management. Available evidence suggests that rapid over standard GS or ES is of greater benefit in the NICU/PICU setting vs. outpatient setting. Future clinical studies must include both diagnostic yield and clinical management outcomes in order to provide stakeholders with the necessary evidence to support decision-making on implementation and coverage.