Care and cost consequences of pediatric whole genome sequencing compared to chromosome microarray

Hayeems, Robin Z.; Bhawra, Jasmin; Tsiplova, Kate; Meyn, Stephen; Monfared, Nasim; Bowdin, Sarah; Stavropoulos, Dimitri J.; Marshall, Christian R.; Basran, Raveen K.; Shuman, Cheryl; Itô, Shinya; Cohn, Iris; Hum, Courtney; Gı̂rdea, Marta; Brudno, Michael; Cohn, Ronald D.; Scherer, Stephen W.; Ungar, Wendy J.

doi:10.1038/s41431-017-0020-3

Cited by 34 publications

(33 citation statements)

References 38 publications

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“…It has been previously shown that WGS, while an expensive test, may actually decrease overall cost (particularly downstream cost) of diagnostic evaluations of medically complex children. 12 Although also appearing to reduce rather than increase costs in our cohort, the impact of precision medicine could not be quantified in seven of 13 infants without a group of matched historical controls and/or long-term follow up (see Supplementary Results ). However, the short-term impact on healthcare utilization was quantified in the remaining six infants (Table 3 , Fig.…”

Section: Resultsmentioning

confidence: 98%

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

et al. 2018

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Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study of acutely ill inpatient infants in a regional children’s hospital from July 2016–March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands also received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (P = .0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; P = .0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000–$2,000,000. These findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.

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Section: Resultsmentioning

confidence: 98%

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

et al. 2018

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“…This is well illustrated by a recent study that compared children with suspected genetic disease who had initial chromosomal microarray analysis and subsequent diagnostic genome sequencing. 14 The volumes and costs of medical interventions prompted by negative chromosomal microarray results and diagnostic GWS results were quantitatively similar but qualitatively different. Negative chromosomal microarray analysis sometimes led to additional laboratory investigations in pursuit of a diagnosis, while obtaining a diagnosis by genome sequencing often led to more visits to medical specialists or allied health professionals, reflecting changes in clinical management.…”

Section: Introductionmentioning

confidence: 98%

Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application?

Friedman

Bombard

Cornel

et al. 2019

Genetics in Medicine

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Diagnostic genome-wide sequencing (exome or genome sequencing and data analysis for high-penetrance disease-causing variants) in acutely ill infants appears to be clinically useful, but the value of this diagnostic test should be rigorously demonstrated before it is accepted as a standard of care. This white paper was developed by the Paediatric Task Team of the Global Alliance for Genomics and Health’s Regulatory and Ethics Work Stream to address the question of how we can determine the clinical value of genome-wide sequencing in infants in an intensive care setting. After reviewing available clinical and ethics literature on this question, we conclude that evaluating diagnostic genome-wide sequencing as a comprehensive scan for major genetic disease (rather than as a large panel of single-gene tests) provides a practical approach to assessing its clinical value in acutely ill infants. Comparing the clinical value of diagnostic genome-wide sequencing to chromosomal microarray analysis, the current evidence-based standard of care, per case of serious genetic disease diagnosed provides a practical means of assessing clinical value. Scientifically rigorous studies of this kind are needed to determine if clinical genome-wide sequencing should be established as a standard of care supported by healthcare systems and insurers for diagnosis of genetic disease in seriously ill newborn infants.

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“…The change in medical management is thus commonly used as an indicator of clinical utility, where a measure of outcome can be captured at three instances: (i) the return of results, (ii) documented changes to clinical management, and (iii) measures of long-term clinical outcome 24 . While many studies focused on describing the changes in acute management brought about by a positive genetic diagnosis, very few have assessed the long-term impact by longitudinal follow-up of >1 year 3 , 19 , 25 – 29 . Furthermore, the impact on reproductive decisions for both the affected individuals and their families is often limited.…”

Section: Introductionmentioning

confidence: 99%

A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis

Fung

Huang

et al. 2020

npj Genom. Med.

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Exome sequencing (ES) has become one of the important diagnostic tools in clinical genetics with a reported diagnostic rate of 25–58%. Many studies have illustrated the diagnostic and immediate clinical impact of ES. However, up to 75% of individuals remain undiagnosed and there is scarce evidence supporting clinical utility beyond a follow-up period of >1 year. This is a 3-year follow-up analysis to our previous publication by Mak et al. (NPJ Genom. Med. 3:19, 2018), to evaluate the long-term clinical utility of ES and the diagnostic potential of exome reanalysis. The diagnostic yield of the initial study was 41% (43/104). Exome reanalysis in 46 undiagnosed individuals has achieved 12 new diagnoses. The additional yield compared with the initial analysis was at least 12% (increased from 41% to at least 53%). After a median follow-up period of 3.4 years, change in clinical management was observed in 72.2% of the individuals (26/36), leading to positive change in clinical outcome in four individuals (11%). There was a minimum healthcare cost saving of HKD$152,078 (USD$19,497; €17,282) annually for these four individuals. There were a total of six pregnancies from five families within the period. Prenatal diagnosis was performed in four pregnancies; one fetus was affected and resulted in termination. None of the parents underwent preimplantation genetic diagnosis. This 3-year follow-up study demonstrated the long-term clinical utility of ES at individual, familial and health system level, and the promising diagnostic potential of subsequent reanalysis. This highlights the benefits of implementing ES and regular reanalysis in the clinical setting.

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Care and cost consequences of pediatric whole genome sequencing compared to chromosome microarray

Cited by 34 publications

References 38 publications

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application?

A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis

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