Open AccessIntegrating exome sequencing into a diagnostic pathway for epileptic encephalopathy: Evidence of clinical utility and cost effectiveness
Author(s) -
Palmer Elizabeth E.,
Schofield Deborah,
Shrestha Rupendra,
Kandula Tejaswi,
Macintosh Rebecca,
Lawson John A.,
Andrews Ian,
Sampaio Hugo,
Johnson Alexandra M.,
Farrar Michelle A.,
Cardamone Michael,
Mowat David,
Elakis George,
Lo William,
Zhu Ying,
Ying Kevin,
Morris Paula,
Tao Jiang,
Dias KerithRae,
Buckley Michael,
Dinger Marcel E.,
Cowley Mark J.,
Roscioli Tony,
Kirk Edwin P.,
Bye Ann,
Sachdev Rani K.
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.355
Subject(s) - exome sequencing , medicine , exome , epilepsy , genetic testing , bioinformatics , cost effectiveness , genetics , mutation , biology , psychiatry , gene , risk analysis (engineering)
Background Epileptic encephalopathies are a devastating group of neurological conditions in which etiological diagnosis can alter management and clinical outcome. Exome sequencing and gene panel testing can improve diagnostic yield but there is no cost‐effectiveness analysis of their use or consensus on how to best integrate these tests into clinical diagnostic pathways. Methods We conducted a retrospective cost‐effectiveness study comparing trio exome sequencing with a standard diagnostic approach, for a well‐phenotyped cohort of 32 patients with epileptic encephalopathy, who remained undiagnosed after “first‐tier” testing. Sensitivity analysis was included with a range of commercial exome and multigene panels. Results The diagnostic yield was higher for the exome sequencing (16/32; 50%) than the standard arm (2/32; 6.2%). The trio exome sequencing pathway was cost‐effective compared to the standard diagnostic pathway with a cost saving of AU $5,236 (95% confidence intervals $2,482; $9,784) per additional diagnosis; the standard pathway cost approximately 10 times more per diagnosis. Sensitivity analysis demonstrated that the majority of commercial exome sequencing and multigene panels studied were also cost‐effective. The clinical utility of all diagnoses was reported. Conclusion Our study supports the integration of exome sequencing and gene panel testing into the diagnostic pathway for epileptic encephalopathy, both in terms of cost effectiveness and clinical utility. We propose a diagnostic pathway that integrates initial rapid screening for treatable causes and comprehensive genomic screening. This study has important implications for health policy and public funding for epileptic encephalopathy and other neurological conditions.