Applying the Clinician-reported Genetic testing Utility InDEx (C-GUIDE) to genome sequencing: further evidence of validity

被引:0
作者
Robin Z. Hayeems
Stephanie Luca
Anna C. E. Hurst
Meagan Cochran
Chelsea Owens
Alomgir Hossain
Lauren Chad
M. Stephen Meyn
Eleanor Pullenayegum
Wendy J. Ungar
David Bick
机构
[1] The Hospital for Sick Children,Child Health Evaluative Sciences
[2] University of Toronto,Institute of Health Policy, Management and Evaluation
[3] University of Alabama at Birmingham,Biostatistics, Design and Analysis Unit
[4] HudsonAlpha Institute for Biotechnology,Division of Clinical and Metabolic Genetics
[5] The Hospital for Sick Children,Department of Pediatrics
[6] The Hospital for Sick Children,Department of Bioethics
[7] University of Toronto,Center for Human Genomics and Precision Medicine
[8] The Hospital for Sick Children,Dalla Lana School of Public Health
[9] The University of Wisconsin School of Medicine and Public Health,undefined
[10] University of Toronto,undefined
[11] Genomics England,undefined
来源
European Journal of Human Genetics | 2022年 / 30卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Genome 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.
引用
收藏
页码:1423 / 1431
页数:8
相关论文
共 123 条
[1]  
Clark MM(2018)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 3 529-39
[2]  
Stark Z(2020)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 23 451-60
[3]  
Farnaes L(2020)Clinical utility of genomic testing: a measurement toolkit NPJ Genom Med 5 3-11
[4]  
Tan TY(2021)Cost-effectiveness of genome-wide sequencing for unexplained developmental disabilities and multiple congenital anomalies Genet Med 23 365-77
[5]  
White SM(1997)Screening for disease AJR Am J Roentgenol 168 124-32
[6]  
Dimmock D(2021)Opportunistic genomic screening. Recommendations of the European Society of Human Genetics Eur J Hum Genet 29 e1766-16
[7]  
Faulkner E(2019)Secondary findings from next-generation sequencing: what does actionable in childhood really mean? Genet Med 21 1403-33
[8]  
Holtorf A-P(2021)A study of elective genome sequencing and pharmacogenetic testing in an unselected population. Molecular Genetics & Genomic Medicine 9 22-86
[9]  
Walton S(2021)The clinical utility of exome and genome sequencing across clinical indications: a systematic review Hum Genet 140 378-30
[10]  
Liu CY(2021)Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing: a systematic review and meta-analysis Genet Med 23 1122-8