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.
N1 - Copyright The Author(s) 2017. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
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.
UR - http://www.scopus.com/inward/record.url?scp=85028675836&partnerID=8YFLogxK
U2 - 10.1038/s41525-017-0006-7
DO - 10.1038/s41525-017-0006-7
M3 - Article
C2 - 29152331
SN - 2056-7944
VL - 2
SP - 1
EP - 7
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 4
ER -