UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders

Nurchis, MC; Radio, FC; Salmasi, L; Heidar Alizadeh, A; Raspolini, GM; Altamura, G; Tartaglia, M; ... Damiani, G; + view all (2024) Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders. JAMA Network Open , 7 (1) , Article e2353514. 10.1001/jamanetworkopen.2023.53514. Green open access

[thumbnail of nurchis_2024_oi_231570_1705675040.72304.pdf]
Preview
PDF
nurchis_2024_oi_231570_1705675040.72304.pdf - Published Version

Download (1MB) | Preview

Abstract

IMPORTANCE The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. OBJECTIVE To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. DESIGN, SETTING, AND PARTICIPANTS In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesù, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. MAIN OUTCOMES AND MEASURES Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. RESULTS The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above €29 800 (US $32 408) per diagnosis that were tested up to €50 000 (US $54 375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. CONCLUSIONS AND RELEVANCE The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access.

Type: Article
Title: Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1001/jamanetworkopen.2023.53514
Publisher version: http://dx.doi.org/10.1001/jamanetworkopen.2023.535...
Language: English
Additional information: © 2024 Nurchis MC et al. JAMA Network Open. This is an open access article distributed under the terms of the CC-BY License.
Keywords: Female, Humans, Child, Male, Exome Sequencing, Cost-Benefit Analysis, Bayes Theorem, Genome, Whole Genome Sequencing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Applied Health Research
URI: https://discovery.ucl.ac.uk/id/eprint/10189032
Downloads since deposit
4Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item