دورية أكاديمية
Protocol for a Prospective, Observational Cost-effectiveness Analysis of Returning Secondary Findings of Genome Sequencing for Unexplained Suspected Genetic Conditions.
| العنوان: | Protocol for a Prospective, Observational Cost-effectiveness Analysis of Returning Secondary Findings of Genome Sequencing for Unexplained Suspected Genetic Conditions. |
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| المؤلفون: | Ungar WJ; Program in Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address: wendy.ungar@sickkids.ca., Hayeems RZ; Program in Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada; Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada., Marshall CR; Genome Diagnostics, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada., Gillespie MK; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada., Szuto A; Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Ontario, Canada., Chisholm C; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., James Stavropoulos D; Genome Diagnostics, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada., Huang L; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Jarinova O; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Wu V; Program in Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada., Tsiplova K; Program in Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada., Lau L; Genome Diagnostics, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada., Lee W; Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Ontario, Canada., Venkataramanan V; Program in Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada., Sawyer S; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada., Mendoza-Londono R; Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Ontario, Canada., Somerville MJ; Genome Diagnostics, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada., Boycott KM; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada. |
| مؤلفون مشاركون: | Genome Sequencing Ontario Secondary Findings Study Team |
| المصدر: | Clinical therapeutics [Clin Ther] 2023 Aug; Vol. 45 (8), pp. 702-709. Date of Electronic Publication: 2023 Jul 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Excerpta Medica Country of Publication: United States NLM ID: 7706726 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-114X (Electronic) Linking ISSN: 01492918 NLM ISO Abbreviation: Clin Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Belle Mead, NJ, : Excerpta Medica Original Publication: Princeton, N. J., Excerpta Medica. |
| مستخلص: | Purpose: Although costly, genome-wide sequencing (GWS) detects an extensive range of variants, enhancing our ability to diagnose and assess risk for an increasing number of diseases. In addition to detecting variants related to the indication for testing, GWS can detect secondary variants in BRCA1, BRCA2, and other genes for which early intervention may improve health. As the list of secondary findings grows, there is increased demand for surveillance and management by multiple specialists, adding pressure to constrained health care budgets. Secondary finding testing is actively debated because some consider it opportunistic screening for future health risks that may not manifest. Given the economic implications of secondary finding testing and follow-up and its unproven clinical utility, the objective is to assess the incremental cost-effectiveness of secondary finding ascertainment per case detected and per unit of improved clinical utility in families of children with unexplained suspected genetic conditions undergoing clinical GWS. Methods: Those undergoing trio genome or exome sequencing are eligible for the study. Positive secondary finding index cases will be matched to negative controls (1:2) based on age group, primary result(s) type, and clinical indication. During the 2-year study, 71 cases and 142 matched controls are expected. Health service use will be collected in patients and 1 adult family member every 6 months. The per-child and per-dyad total cost will be determined by multiplying use of each resource by a corresponding unit price and summing all cost items. Costs will be estimated from the public and societal payer perspectives. The mean cost per child and per dyad for secondary finding-positive and secondary finding-negative groups will be compared statistically. If important demographic differences are observed between groups, ordinary least-squares regression, log transformation, or other nonparametric technique will be used to compare adjusted mean costs. The ratio of the difference in mean cost to the secondary finding yield will be used to estimate incremental cost-effectiveness. In secondary analyses, effectiveness will be estimated using the number of clinical management changes due to secondary findings or the Clinician-Reported Genetic Testing Utility Index (C-GUIDE) score, a validated measure of clinical utility. Sensitivity analysis will be undertaken to assess the robustness of the findings to variation in key parameters. Implications: This study generates key evidence to inform clinical practice and funding allocation related to secondary finding testing. The inclusion of family members and a new measure of clinical utility represent important advancements in economic evaluation in genomics. Competing Interests: Declaration of Competing Interest Wendy J. Ungar reported receiving grant funding from Canadian Institutes of Health Research, Genome Canada, and Ontario Genomics Institute, serving as chair of the Ontario Genetics Advisory Committee, and serving as a member of the Ontario Health Technology Assessment Advisory Committee. Robin Z. Hayeems reported receiving grant funding from Canadian Institutes of Health Research. Christian R. Marshall reported receiving honoraria and travel funds from Illumina for an American Society of Human Genetics conference presentation in 2022. D. James Stavropoulos reported having stocks or stock options in Phenotips. The authors have indicated that they have no other conflicts of interest regarding the content of this article. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Child health; Cost-effectiveness analysis; Genome sequencing; Neurodevelopmental disorders; Secondary findings |
| تواريخ الأحداث: | Date Created: 20230715 Latest Revision: 20230902 |
| رمز التحديث: | 20230903 |
| DOI: | 10.1016/j.clinthera.2023.06.004 |
| PMID: | 37453830 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1879-114X |
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| DOI: | 10.1016/j.clinthera.2023.06.004 |