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Pediatric Genetic Diagnoses Cost-Effective With First-Tier WGS, Economic Study Suggests

NEW YORK – Using an economic modeling approach, a team from Italy and the UK suggests that first-line whole-genome sequencing (WGS) may be a cost-effective alternative to standard-of-care testing, first- or second-tier whole-exome sequencing (WES), or second-tier WGS when it comes to diagnosing suspected genetic conditions in pediatric patients.

"Our findings contribute to previous studies exploring the cost-effectiveness of WGS and WES," first and corresponding author Mario Cesare Nurchis, a researcher at the Catholic University of the Sacred Heart in Rome, and his colleagues wrote in JAMA Network Open on Friday, adding that the work "informs nuanced decision-making throughout the healthcare landscape."

For their study, the researchers brought together hospital data and published analyses on clinical management and cost assessments to analyze the diagnostic yields and cost-effectiveness of standard-of-care genetic testing, WGS, and WES in 870 yet-to-be-diagnosed pediatric cases. The participants were enrolled in the Bambino Gesù Pediatric Hospital's Undiagnosed Patients Program in Rome from 2015 through 2022 and ranged in age from infancy to 18 years old.

"Clinical suspicion for each patient was based on results of a multidisciplinary evaluation, including craniofacial appearance, anthropometric measurements, and a detailed clinical appraisal on a case-to-case basis," the authors explained, noting that this "guided the selection of WES or WGS analyses based on the clinical spectrum and/or results of previously performed testing."

While standard-of-care genetic testing carried the lowest cost, the team explained, it also achieved fewer diagnoses than the WGS- or WES-based approaches. Together with past research pointing to dips in additional healthcare costs after WGS-based diagnoses, the results hinted that the downstream cost-effectiveness and increased diagnostic yield of first-line WGS may offset the initial increase in cost.

"These findings suggest that wider use of WGS may minimize diagnostic delays and facilitate timely implementation of appropriate treatments," the authors noted.

When they used Bayesian Markov and Markov chain Monte Carlo algorithms and simulations to compare the cost and diagnostic yields for first-tier WGS, first-tier WES, second-tier WGS, or second-tier WGS, for example, the researchers estimated that WGS would be a cost-effective alternative to standard-of-care testing, first- or second-line WES, or second-line WGS assuming a "willingness-to-pay" (WTP) threshold of $32,625 and $54,375 per diagnosis.

The investigators cautioned that their analyses focused on cost-effectiveness in relation to the pediatric patients' clinical outcomes rather than looking at quality-adjusted life year measurements. In addition, they noted that the current cost-effectiveness models did not consider the potential diagnostic benefits of reanalyzing existing exome sequence data, nor did it delve into the costs associated with data storage or the extra variant interpretation efforts needed to interrogate noncoding variants uncovered by WGS.

Even so, the study's authors argued that the work "champions WGS over WES as a first-tier diagnostic strategy for its cost-effectiveness, especially for children with suspected rare diseases," and argued that the National Health Service in Italy "needs policy shifts for efficient WGS adoption that are reinforced by further clinical and economic evidence."