Clinical utility of genomic sequencing: a measurement toolkit

Hayeems, Robin Z.; Dimmock, David; Bick, David; Belmont, John W.; Green, Robert C; Lanpher, Brendan C.; Jobanputra, Vaidehi; Mendoza, Roberto; Kulkarni, Shashi; Grove, Megan E.; Taylor, Stacie L.; Ashley, Euan A.; Initiative, Medical Genome

doi:10.1038/s41525-020-00164-7

Cited by 41 publications

(40 citation statements)

References 91 publications

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“…Ample knowledge of incidence, prevailing genotype (like in the cases of CF and SMA) if such exists, population-specific data on gene variants, and detailed natural history for the condition would be necessary for objective decision-making regarding reporting of variants ( Chien et al, 2017 ; Czibere et al, 2020 ). We propose that a unified methodology be used for the assessment of the actionability of the conditions and variants ( Milko et al, 2019 ; Hayeems et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing in Newborn Screening: A Review of Current State

et al. 2021

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Newborn screening was first introduced at the beginning of the 1960s with the successful implementation of the first phenylketonuria screening programs. Early expansion of the included disorders was slow because each additional disorder screened required a separate test. Subsequently, the technological advancements of biochemical methodology enabled the scaling-up of newborn screening, most notably with the implementation of tandem mass spectrometry. In recent years, we have witnessed a remarkable progression of high-throughput sequencing technologies, which has resulted in a continuous decrease of both cost and time required for genetic analysis. This has enabled more widespread use of the massive multiparallel sequencing. Genomic sequencing is now frequently used in clinical applications, and its implementation in newborn screening has been intensively advocated. The expansion of newborn screening has raised many clinical, ethical, legal, psychological, sociological, and technological concerns over time. This review provides an overview of the current state of next-generation sequencing regarding newborn screening including current recommendations and potential challenges for the use of such technologies in newborn screening.

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Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing in Newborn Screening: A Review of Current State

et al. 2021

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“…While it is generally agreed that personal and perceived utility reflect on the subjective meaning an individual ascribes to genetic testing, consensus has not emerged on the precise definition of these and related constructs. For example, whether or not elements of these constructs are distinct from or overlapping with elements of clinical utility or with elements of psychosocial well-being remains contested [ 9 , 16 , 63 ]. In addition, some orient to personal and perceived utility as measures of anticipated (i.e., pre-test) value [ 72 , 73 ], some as a measure of actual (i.e., post-test) value [ 15 , 20 , 74 , 75 ], and some as a composite of both [ 16 , 17 , 70 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

“…Defining and measuring the notion of benefit in the context of genome diagnostics requires the inclusion of metrics that extend beyond laboratory-based performance and incorporate patients’ perspectives [ 6 , 7 , 8 , 9 ]. This requirement aligns with a broader transformation in clinical research that has prioritized ascertaining patient and family experiences [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Utility of Genetic Testing from the Perspective of Parents/Caregivers: A Scoping Review

et al. 2021

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In genomics, perceived and personal utility have been proposed as constructs of value that include the subjective meanings and uses of genetic testing. Precisely what constitutes these constructs of utility and how they vary by stakeholder perspective remains unresolved. To advance methods for measuring the value of genetic testing in child health, we conducted a scoping review of the literature to characterize utility from the perspective of parents/caregivers. Peer reviewed literature that included empiric findings from parents/caregivers who received genetic test results for an index child and was written in English from 2016–2020 was included. Identified concepts of utility were coded according to Kohler’s construct of personal utility. Of 2142 abstracts screened, 33 met inclusion criteria. Studies reflected a range of genetic test types; the majority of testing was pursued for children with developmental or neurodevelopmental concerns. Coding resulted in 15 elements of utility that mapped to Kohler’s four domains of personal utility (affective, cognitive, behavioural and social) and one additional medical management domain. An adapted construct of utility for parents/caregivers may enable specific and standardized strategies for researchers to use to generate evidence of the post-test value of genetic testing. In turn, this will contribute to emerging methods for health technology assessment and policy decision making for genomics in child health.

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“…Decreasing costs and dramatic improvements in next-generation sequencing (NGS) have allowed research and clinical diagnostic laboratories to establish analytical pipelines centered on NGS genomic technologies such as exome sequencing (ES). [1][2][3][4] In particular, clinical laboratories often use ES as a first-tier testing tool to diagnose rare genetic disorders through clinical interpretation of detected variants. [5][6][7] One of the first steps in this process involves the alignment of short reads generated from ES to a haploid human reference genome sequence.…”

Section: Introductionmentioning

confidence: 99%