A cost-effectiveness analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients

Yeung, Alison; Tan, Natalie B; Tan, Tiong Yang; Stark, Zornitza; Brown, Natasha J; Hunter, Matthew; Delatycki, Martin B.; Stutterd, Chloe; Savarirayan, Ravi; McGillivray, George; Stapleton, Rachel; Kumble, Smitha; Downie, Lilian; Regan, Matthew; Lunke, Sebastian; Chong, Belinda; Phelan, Dean; Brett, Gemma R; Jarmolowicz, Anna; Prawer, Yael; Valente, Giulia; Smagarinsky, Yana; Martyn, Melissa; McEwan, Callum; Goranitis, Ilias; Gaff, Clara; White, Susan

doi:10.1038/s41436-020-0929-8

Cited by 26 publications

(23 citation statements)

References 38 publications

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“…The commitment to make WES a frontline analysis is not new 31. On one hand, it has already been shown that WES can be much more efficient than traditional methods in terms of diagnostic rates as well as cost-effectiveness 32. On the other hand, WES has already shown its superiority against some routine genetic analyses such as gene panels and single gene testing 28 33.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

et al. 2022

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BackgroundDespite the availability of whole exome (WES) and genome sequencing (WGS), chromosomal microarray (CMA) remains the first-line diagnostic test in most rare disorders diagnostic workup, looking for copy number variations (CNVs), with a diagnostic yield of 10%–20%. The question of the equivalence of CMA and WES in CNV calling is an organisational and economic question, especially when ordering a WGS after a negative CMA and/or WES.MethodsThis study measures the equivalence between CMA and GATK4 exome sequencing depth of coverage method in detecting coding CNVs on a retrospective cohort of 615 unrelated individuals. A prospective detection of WES-CNV on a cohort of 2418 unrelated individuals, including the 615 individuals from the validation cohort, was performed.ResultsOn the retrospective validation cohort, every CNV detectable by the method (ie, a CNV with at least one exon not in a dark zone) was accurately called (64/64 events). In the prospective cohort, 32 diagnoses were performed among the 2418 individuals with CNVs ranging from 704 bp to aneuploidy. An incidental finding was reported. The overall increase in diagnostic yield was of 1.7%, varying from 1.2% in individuals with multiple congenital anomalies to 1.9% in individuals with chronic kidney failure.ConclusionCombining single-nucleotide variant (SNV) and CNV detection increases the suitability of exome sequencing as a first-tier diagnostic test for suspected rare Mendelian disorders. Before considering the prescription of a WGS after a negative WES, a careful reanalysis with updated CNV calling and SNV annotation should be considered.

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Section: Discussionmentioning

confidence: 99%

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

et al. 2022

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“…The costs of standard diagnostic care for children were estimated by pooling estimates from studies that evaluated ES in patients without a diagnosis after standard workup and reported mean follow up of standard diagnosis. 20,32,34,35 Costs for infants were based on the study by Stark et al 15 and were converted to US dollars from Australian dollars or Euros. In both cases, we assumed that patients would continue to receive diagnostic tests as long as they were undiagnosed.…”

Section: Costs Of Diagnostic Carementioning

confidence: 99%

Cost-effectiveness of genome sequencing for diagnosing patients with undiagnosed rare genetic diseases

Incerti¹,

Xu²,

Chou³

et al. 2022

Genetics in Medicine

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To estimate the cost-effectiveness of genome sequencing (GS) for diagnosing critically ill infants and noncritically ill pediatric patients (children) with suspected rare genetic diseases from a United States health sector perspective. Methods: A decision-analytic model was developed to simulate the diagnostic trajectory of patients. Parameter estimates were derived from a targeted literature review and metaanalysis. The model simulated clinical and economic outcomes associated with 3 diagnostic pathways: (1) standard diagnostic care, (2) GS, and (3) standard diagnostic care followed by GS. Results: For children, costs of GS ($7284) were similar to that of standard care ($7355) and lower than that of standard care followed by GS pathways ($12,030). In critically ill infants, when cost estimates were based on the length of stay in the neonatal intensive care unit, the lowest cost pathway was GS

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“…Although long-term management was not included in this analysis, given the significant cost savings observed in children, these savings are unlikely to be offset by future management costs among a proportion of children for whom ES demonstrates clinical utility. 51 When comparing genomic approaches, integrating ES with targeted analysis early in the diagnostic pathway is the most cost-effective genomic approach. ES should be prioritized over conventional panels due to similarities in cost and greater diagnostic yield.…”

Section: Discussionmentioning

confidence: 99%

“…Further research that considers the long-term clinical implications of genomic testing across all Genetic Kidney Disease is required to establish the cost-effectiveness of genomic investigations in kidney disease. 51…”

Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness of Targeted Exome Analysis as a Diagnostic Test in Glomerular Diseases

Jayasinghe

Stark

et al. 2021

Kidney International Reports

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Background: Despite the emergence of diagnostic and clinical utility evidence in nephrology, publicly funded access to genomic testing is restricted in most health care systems. To establish genomic sequencing as a clinical test, an evaluation of cost-effectiveness is urgently required.Methods: An economic evaluation, informed by a primary clinical study and available clinical evidence and guidelines in nephrology, was performed to evaluate the cost-effectiveness and optimal timing of exome sequencing (ES) in adults and children with suspected monogenic glomerular diseases compared with nongenomic investigations (NGIs). Six diagnostic strategies reflecting current practice and recommended models of care in Australia were modeled: (i) NGIs, (ii) late gene panel followed by ES, (iii) late ES, (iv) early gene panel, (v) early gene panel followed by ES, and (vi) early ES.Results: ES with targeted analysis achieved a diagnosis in 23 of 63 (36.5%) adults and 10 of 24 (41.6%) children. NGIs were estimated to diagnose 4.0% of children, with an average estimated cost of AU$6120 per child. Integrating ES as a first-line test in children was cost saving, with an incremental cost saving of AU$3230 per additional diagnosis compared with NGIs. In adults, NGIs was estimated to diagnose 8% of patients, with an average estimated cost of AU$1830 per person. In adults, integrating ES early resulted in an incremental cost per additional diagnosis of AU$5460 relative to NGIs.Conclusions: Early ES with targeted analysis was effective for diagnosing monogenic kidney disease, with substantial cost savings in children.

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A cost-effectiveness analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients

Cited by 26 publications

References 38 publications

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

Exome sequencing as a first-tier test for copy number variant detection: retrospective evaluation and prospective screening in 2418 cases

Cost-effectiveness of genome sequencing for diagnosing patients with undiagnosed rare genetic diseases

Cost-Effectiveness of Targeted Exome Analysis as a Diagnostic Test in Glomerular Diseases

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