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

Deborah Schofield, Khurshid Alam, Lyndal Douglas, Rupendra Shrestha, Daniel G MacArthur, Mark Davis, Nigel G Laing, Nigel F Clarke, Joshua Burns, Sandra T Cooper, Kathryn N North, Sarah A Sandaradura, Gina L O'Grady

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalGenome Medicine
Volume2
DOIs
Publication statusPublished - 2017

Fingerprint

High-Throughput Nucleotide Sequencing
Exome
Neuromuscular Diseases
Cost-Benefit Analysis
Pediatrics
Muscles
Biopsy
Costs and Cost Analysis
Nemaline Myopathies
Government Financing
Technology
Muscle Proteins
Muscular Dystrophies
Muscular Diseases
Rare Diseases
Genes

Cite this

Schofield, D., Alam, K., Douglas, L., Shrestha, R., MacArthur, D. G., Davis, M., ... O'Grady, G. L. (2017). Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases. Genome Medicine, 2. https://doi.org/10.1038/s41525-017-0006-7
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. In: Genome Medicine. 2017 ; Vol. 2.
@article{d77f9e1cfdfc4eaabc0f9b2159533630,
title = "Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases",
abstract = "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.",
keywords = "Journal Article",
author = "Deborah Schofield and Khurshid Alam and Lyndal Douglas and Rupendra Shrestha and MacArthur, {Daniel G} and Mark Davis and Laing, {Nigel G} and Clarke, {Nigel F} and Joshua Burns and Cooper, {Sandra T} and North, {Kathryn N} and Sandaradura, {Sarah A} and O'Grady, {Gina L}",
year = "2017",
doi = "10.1038/s41525-017-0006-7",
language = "English",
volume = "2",
journal = "Genome Medicine",
issn = "1756-994X",
publisher = "BioMed Central",

}

Schofield, D, Alam, K, Douglas, L, Shrestha, R, MacArthur, DG, Davis, M, Laing, NG, Clarke, NF, Burns, J, Cooper, ST, North, KN, Sandaradura, SA & O'Grady, GL 2017, 'Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases' Genome Medicine, vol. 2. https://doi.org/10.1038/s41525-017-0006-7

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.

In: Genome Medicine, Vol. 2, 2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases

AU - Schofield, Deborah

AU - Alam, Khurshid

AU - Douglas, Lyndal

AU - Shrestha, Rupendra

AU - MacArthur, Daniel G

AU - Davis, Mark

AU - Laing, Nigel G

AU - Clarke, Nigel F

AU - Burns, Joshua

AU - Cooper, Sandra T

AU - North, Kathryn N

AU - Sandaradura, Sarah A

AU - O'Grady, Gina L

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41525-017-0006-7

DO - 10.1038/s41525-017-0006-7

M3 - Article

VL - 2

JO - Genome Medicine

JF - Genome Medicine

SN - 1756-994X

ER -