Abstract
AbstractGenome sequencing (GS) outperforms other rare disease diagnostics, but standardized approaches to assessing its clinical utility are limited. This study assessed the validity of the Clinician-reported Genetic testing Utility InDEx (C-GUIDE), a novel tool for assessing the utility of genetic testing from a clinician’s perspective, for GS. C-GUIDE ratings were completed for patients who received GS results. For each patient, total C-GUIDE and single item global scores were calculated. Construct validity was assessed using linear regression to determine the association between C-GUIDE total and global item scores and measure the effects of potential explanatory variables. Ratings were completed for 67 pediatric and 36 adult patients. GS indications were neurological for 70.9% and results were diagnostic for 28.2%. When the C-GUIDE assessed primary (PV), secondary (SV), and pharmacogenomic (PGx) variants, on average, a one unit increase in the global item score was associated with an increase of 7.3 in the C-GUIDE score (p < 0.05). Diagnostic results were associated with an increase in C-GUIDE score of 5.0 compared to non-diagnostic results (p < 0.05) and an increase of one SV was associated with an increase of 2.5 (p < 0.05). For children, decreased age of one year was associated with an increase in C-GUIDE score of 0.3 (p < 0.05). Findings provide evidence that C-GUIDE measures the construct of clinical utility in pediatric and adult rare disease populations and is sensitive to changes in utility related to variant type. Quantifying the clinical utility of GS using C-GUIDE can inform efforts to optimize its use in patient care.
Funder
Gouvernement du Canada | Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Reference32 articles.
1. Clark MM, Stark Z, Farnaes L, Tan TY, White SM, Dimmock D, et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom Med. 2018;3:16.
2. Faulkner E, Holtorf A-P, Walton S, Liu CY, Lin H, Biltaj E, et al. Being precise about precision medicine: what should value frameworks incorporate to address precision medicine? A report of the personalized precision medicine special interest group. Value Health. 2020;23:529–39.
3. Hayeems RZ, Dimmock D, Bick D, Belmont JW, Green RC, Lanpher B, et al. Clinical utility of genomic testing: a measurement toolkit. NPJ Genom Med. 2020;5:56.
4. Li C, Vandersluis S, Holubowich C, Ungar WJ, Goh ES, Boycott KM, et al. Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies. Genet Med. 2021;23:451–60.
5. Ontario Health Quality. Genome-wide sequencing for unexplained developmental disabilities or multiple congenital anomalies: a health technology assessment 2020. Available from: https://www.hqontario.ca/Portals/0/Documents/evidence/reports/hta-genome-wide-sequencing.pdf.
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