TY - JOUR
T1 - Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders
AU - Nurchis, Mario Cesare
AU - Nurchis, Mario Cesare
AU - Radio, Francesca Clementina
AU - Salmasi, Luca
AU - Heidar Alizadeh, Aurora
AU - Raspolini, Gian Marco
AU - Altamura, Gerardo Andrea
AU - Tartaglia, Marco
AU - Dallapiccola, Bruno
AU - Pizzo, Elena
AU - Gianino, Maria Michela
AU - Damiani, Gianfranco
PY - 2024
Y1 - 2024
N2 - 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 Gesu, 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 euro29 800 (US $32 408) per diagnosis that were tested up to euro50 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.
AB - 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 Gesu, 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 euro29 800 (US $32 408) per diagnosis that were tested up to euro50 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.
KW - Bayesian modelling
KW - Health policy
KW - Pediatric population
KW - Whole exome sequencing
KW - Whole genome sequencing
KW - Bayesian modelling
KW - Health policy
KW - Pediatric population
KW - Whole exome sequencing
KW - Whole genome sequencing
UR - http://hdl.handle.net/10807/262385
U2 - 10.1001/jamanetworkopen.2023.53514
DO - 10.1001/jamanetworkopen.2023.53514
M3 - Article
SN - 2574-3805
VL - 7
SP - e2353514-N/A
JO - JAMA network open
JF - JAMA network open
ER -