Genomic sequencing in acutely ill infants: what will it take to demonstrate clinical value?

Grosse, Scott D.; Farnaes, Lauge

doi:10.1038/s41436-018-0124-3

Cited by 18 publications

(15 citation statements)

References 11 publications

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“…From these, we identified proxy measures of clinical decision making and process changes and combined these with the types of changes in management observed in previous studies of genomic sequencing in ICUs. [12][13][14]16,17,19,[26][27][28][29][30][31][32][33] From these, we devised 35 questions to evaluate benefit and harm perceived by clinicians and clinical teams (Supplemental Data). Draft questions were reviewed by NICU providers and pediatric subspecialists to ensure consistency and clarity.…”

Section: Clinician Surveymentioning

confidence: 99%

“…[26][27][28][29][30][31] As such, generating and evaluating evidence of clinical utility is complex. 32 This challenge is compounded by the variety of clinical presentations in the NICU, PICU, and CVICU, the multitude of disorders that can be diagnosed with genome-wide sequencing, and a range of outcomes. To date, very little data have been gathered on the potential risks of the deployment of rapid genome-wide sequencing in infants in NICU, PICU, and CVICU settings.…”

Section: Introductionmentioning

confidence: 99%

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An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm

Dimmock¹,

Clark²,

Gaughran³

et al. 2020

The American Journal of Human Genetics

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137

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The second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2) study was a randomized, controlled trial of rapid whole-genome sequencing (rWGS) or rapid whole-exome sequencing (rWES) in infants with diseases of unknown etiology in intensive care units (ICUs). Gravely ill infants were not randomized and received ultra-rapid whole-genome sequencing (urWGS). Herein we report results of clinician surveys of the clinical utility of rapid genomic sequencing (RGS). The primary end-point-clinician perception that RGS was useful-was met for 154 (77%) of 201 infants. Both positive and negative tests were rated as having clinical utility (42 of 45 [93%] and 112 of 156 [72%], respectively). Physicians reported that RGS changed clinical management in 57 (28%) infants, particularly in those receiving urWGS (p ¼ 0.0001) and positive tests (p < 0.00001). Outcomes of 32 (15%) infants were perceived to be changed by RGS. Positive tests changed outcomes more frequently than negative tests (p < 0.00001). In logistic regression models, the likelihood that RGS was perceived as useful increased 6.7-fold when associated with changes in management (95% CI 1.8-43.3). Changes in management were 10.1-fold more likely when results were positive (95% CI 4.7-22.4) and turnaround time was shorter (odds ratio 0.92, 95% CI 0.85-0.99). RGS seldom led to clinician-perceived confusion or distress among families (6 of 207 [3%]). In summary, clinicians perceived high clinical utility and low likelihood of harm with first-tier RGS of infants in ICUs with diseases of unknown etiology. RGS was perceived as beneficial irrespective of whether results were positive or negative.

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Section: Clinician Surveymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm

Dimmock¹,

Clark²,

Gaughran³

et al. 2020

The American Journal of Human Genetics

Self Cite

137

View full text Add to dashboard Cite

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“…Additionally, only a modest number of groups have endeavored to include QALYs as the outcome measure in their economic analyses, as recommended by major health technology assessment agencies when performing a cost-utility analysis ( 4 , 14 , 18 , 19 ). The QALY is the preferred metric because it combines two different benefits attributed to a particular intervention- longevity and quality of life- into a single number that can be compared between alternative interventions ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Cost Efficacy of Rapid Whole Genome Sequencing in the Pediatric Intensive Care Unit

et al. 2022

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The diagnostic and clinical utility of rapid whole genome sequencing (rWGS) for critically ill children in the intensive care unit (ICU) has been substantiated by multiple studies, but comprehensive cost-effectiveness evaluation of rWGS in the ICU outside of the neonatal age group is lacking. In this study, we examined cost data retrospectively for a cohort of 38 children in a regional pediatric ICU (PICU) who received rWGS. We identified seven of 17 patients who received molecular diagnoses by rWGS and had resultant changes in clinical management with sufficient clarity to permit cost and quality adjusted life years (QALY) modeling. Cost of PICU care was estimated to be reduced by $184,846 and a total of 12.1 QALYs were gained among these seven patients. The total cost of rWGS for patients and families for the entire cohort (38 probands) was $239,400. Thus, the net cost of rWGS was $54,554, representing $4,509 per QALY gained. This quantitative, retrospective examination of healthcare utilization associated with rWGS-informed medicine interventions in the PICU revealed approximately one-third of a QALY gained per patient tested at a cost per QALY that was approximately one-tenth of that typically sought for cost-effective new medical interventions. This evidence suggests that performance of rWGS as a first-tier test in selected PICU children with diseases of unknown etiology is associated with acceptable cost-per-QALY gained.

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“…1,[4][5][6] Indeed, it has been suggested that NICU may be one of the areas where diagnostic genetic testing has its greatest impact. 7,8 Multiple tests are currently used to identify these diagnoses, from chromosomal testing such as karyotyping and chromosomal microarray (CMA) to sequencing tests, including gene panels focusing on a particular indication. More recently, broader genomic evaluation with gene panels comprising thousands of genes, exome sequencing (ES), or genome sequencing (GS) has become available and has been shown to be of high yield and clinically effective.…”

Section: Introductionmentioning

confidence: 99%

Perspectives of United States neonatologists on genetic testing practices

Wojcik

Rosario

Agrawal

2022

Genetics in Medicine

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Genomic sequencing in acutely ill infants: what will it take to demonstrate clinical value?

Cited by 18 publications

References 11 publications

An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm

An RCT of Rapid Genomic Sequencing among Seriously Ill Infants Results in High Clinical Utility, Changes in Management, and Low Perceived Harm

Cost Efficacy of Rapid Whole Genome Sequencing in the Pediatric Intensive Care Unit

Perspectives of United States neonatologists on genetic testing practices

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