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Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases

Childhood-onset muscle disorders are genetically heterogeneous. Diagnostic workup has traditionally included muscle biopsy, protein-based studies of muscle specimens, and candidate gene sequencing. High throughput or massively parallel sequencing is transforming the approach to diagnosis of rare dis...

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Autores principales: Schofield, Deborah, Alam, Khurshid, Douglas, Lyndal, Shrestha, Rupendra, MacArthur, Daniel G., Davis, Mark, Laing, Nigel G., Clarke, Nigel F., Burns, Joshua, Cooper, Sandra T., North, Kathryn N., Sandaradura, Sarah A., O’Grady, Gina L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677979/
https://www.ncbi.nlm.nih.gov/pubmed/29152331
http://dx.doi.org/10.1038/s41525-017-0006-7
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author Schofield, Deborah
Alam, Khurshid
Douglas, Lyndal
Shrestha, Rupendra
MacArthur, Daniel G.
Davis, Mark
Laing, Nigel G.
Clarke, Nigel F.
Burns, Joshua
Cooper, Sandra T.
North, Kathryn N.
Sandaradura, Sarah A.
O’Grady, Gina L.
author_facet Schofield, Deborah
Alam, Khurshid
Douglas, Lyndal
Shrestha, Rupendra
MacArthur, Daniel G.
Davis, Mark
Laing, Nigel G.
Clarke, Nigel F.
Burns, Joshua
Cooper, Sandra T.
North, Kathryn N.
Sandaradura, Sarah A.
O’Grady, Gina L.
author_sort Schofield, Deborah
collection PubMed
description Childhood-onset muscle disorders are genetically heterogeneous. Diagnostic workup has traditionally included muscle biopsy, protein-based studies of muscle specimens, and candidate gene sequencing. High throughput or massively parallel sequencing is transforming the approach to diagnosis of rare diseases; however, evidence for cost-effectiveness is lacking. Patients presenting with suspected congenital muscular dystrophy or nemaline myopathy were ascertained over a 15-year period. Patients were investigated using traditional diagnostic approaches. Undiagnosed patients were investigated using either massively parallel sequencing of a panel of neuromuscular disease genes panel, or whole exome sequencing. Cost data were collected for all diagnostic investigations. The diagnostic yield and cost effectiveness of a molecular approach to diagnosis, prior to muscle biopsy, were compared with the traditional approach. Fifty-six patients were analysed. Compared with the traditional invasive muscle biopsy approach, both the neuromuscular disease panel and whole exome sequencing had significantly increased diagnostic yields (from 46 to 75% for the neuromuscular disease panel, and 79% for whole exome sequencing), and reduced the cost per diagnosis from USD$16,495 (95% CI: $12,413–$22,994) to USD$3706 (95% CI: $3086–$4453) for the neuromuscular disease panel and USD$5646 (95% CI: $4501–$7078) for whole exome sequencing. The neuromuscular disease panel was the most cost-effective, saving USD$17,075 (95% CI: $10,654–$30,064) per additional diagnosis, over the traditional diagnostic pathway. Whole exome sequencing saved USD$10,024 (95% CI: $5795–$17,135) per additional diagnosis. This study demonstrates the cost-effectiveness of investigation using massively parallel sequencing technologies in paediatric muscle disease. The findings emphasise the value of implementing these technologies in clinical practice, with particular application for diagnosis of Mendelian diseases, and provide evidence crucial for government subsidy and equitable access.
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spelling pubmed-56779792017-11-17 Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases Schofield, Deborah Alam, Khurshid Douglas, Lyndal Shrestha, Rupendra MacArthur, Daniel G. Davis, Mark Laing, Nigel G. Clarke, Nigel F. Burns, Joshua Cooper, Sandra T. North, Kathryn N. Sandaradura, Sarah A. O’Grady, Gina L. NPJ Genom Med Perspective Childhood-onset muscle disorders are genetically heterogeneous. Diagnostic workup has traditionally included muscle biopsy, protein-based studies of muscle specimens, and candidate gene sequencing. High throughput or massively parallel sequencing is transforming the approach to diagnosis of rare diseases; however, evidence for cost-effectiveness is lacking. Patients presenting with suspected congenital muscular dystrophy or nemaline myopathy were ascertained over a 15-year period. Patients were investigated using traditional diagnostic approaches. Undiagnosed patients were investigated using either massively parallel sequencing of a panel of neuromuscular disease genes panel, or whole exome sequencing. Cost data were collected for all diagnostic investigations. The diagnostic yield and cost effectiveness of a molecular approach to diagnosis, prior to muscle biopsy, were compared with the traditional approach. Fifty-six patients were analysed. Compared with the traditional invasive muscle biopsy approach, both the neuromuscular disease panel and whole exome sequencing had significantly increased diagnostic yields (from 46 to 75% for the neuromuscular disease panel, and 79% for whole exome sequencing), and reduced the cost per diagnosis from USD$16,495 (95% CI: $12,413–$22,994) to USD$3706 (95% CI: $3086–$4453) for the neuromuscular disease panel and USD$5646 (95% CI: $4501–$7078) for whole exome sequencing. The neuromuscular disease panel was the most cost-effective, saving USD$17,075 (95% CI: $10,654–$30,064) per additional diagnosis, over the traditional diagnostic pathway. Whole exome sequencing saved USD$10,024 (95% CI: $5795–$17,135) per additional diagnosis. This study demonstrates the cost-effectiveness of investigation using massively parallel sequencing technologies in paediatric muscle disease. The findings emphasise the value of implementing these technologies in clinical practice, with particular application for diagnosis of Mendelian diseases, and provide evidence crucial for government subsidy and equitable access. Nature Publishing Group UK 2017-03-03 /pmc/articles/PMC5677979/ /pubmed/29152331 http://dx.doi.org/10.1038/s41525-017-0006-7 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Perspective
Schofield, Deborah
Alam, Khurshid
Douglas, Lyndal
Shrestha, Rupendra
MacArthur, Daniel G.
Davis, Mark
Laing, Nigel G.
Clarke, Nigel F.
Burns, Joshua
Cooper, Sandra T.
North, Kathryn N.
Sandaradura, Sarah A.
O’Grady, Gina L.
Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
title Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
title_full Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
title_fullStr Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
title_full_unstemmed Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
title_short Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
title_sort cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677979/
https://www.ncbi.nlm.nih.gov/pubmed/29152331
http://dx.doi.org/10.1038/s41525-017-0006-7
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