Diagnostic yield of genetic tests in epilepsy: A meta-analysis and cost-effectiveness study

Iván Sánchez Fernández; Tobias Loddenkemper; Marina Gaínza-Lein; Beth Rosen Sheidley; Annapurna Poduri

doi:10.1212/WNL.0000000000006850

Diagnostic yield of genetic tests in epilepsy: A meta-analysis and cost-effectiveness study

Neurology. 2019 Jan 28;92(5):e418-e428. doi: 10.1212/WNL.0000000000006850.

Authors

Iván Sánchez Fernández¹, Tobias Loddenkemper¹, Marina Gaínza-Lein¹, Beth Rosen Sheidley¹, Annapurna Poduri²

Affiliations

¹ From the Epilepsy Genetics Program (B.R.S., A.P.), Division of Epilepsy and Clinical Neurophysiology (I.S.F., T.L., M.G.-L., B.R.S., A.P.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, Universidad de Barcelona, Spain; and Facultad de Medicina (M.G.-L.), Universidad Austral de Chile, Valdivia.
² From the Epilepsy Genetics Program (B.R.S., A.P.), Division of Epilepsy and Clinical Neurophysiology (I.S.F., T.L., M.G.-L., B.R.S., A.P.), Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, Universidad de Barcelona, Spain; and Facultad de Medicina (M.G.-L.), Universidad Austral de Chile, Valdivia. annapurna.poduri@childrens.harvard.edu.

Abstract

Objective: To compare the cost-effectiveness of genetic testing strategies in patients with epilepsy of unknown etiology.

Methods: This meta-analysis and cost-effectiveness study compared strategies involving 3 genetic tests: chromosomal microarray (CMA), epilepsy panel (EP) with deletion/duplication testing, and whole-exome sequencing (WES) in a cost-effectiveness model, using "no genetic testing" as a point of comparison.

Results: Twenty studies provided information on the diagnostic yield of CMA (8 studies), EP (9 studies), and WES (6 studies). The diagnostic yield was highest for WES: 0.45 (95% confidence interval [CI]: 0.33-0.57) (0.32 [95% CI: 0.22-0.44] adjusting for potential publication bias), followed by EP: 0.23 (95% CI: 0.18-0.29), and CMA: 0.08 (95% CI: 0.06-0.12). The most cost-effective test was WES with an incremental cost-effectiveness ratio (ICER) of $15,000/diagnosis. However, after adjusting for potential publication bias, the most cost-effective test was EP (ICER: $15,848/diagnosis) followed by WES (ICER: $34,500/diagnosis). Among combination strategies, the most cost-effective strategy was WES, then if nondiagnostic, EP, then if nondiagnostic, CMA (ICER: $15,336/diagnosis), although adjusting for potential publication bias, the most cost-effective strategy was EP ± CMA ± WES (ICER: $18,385/diagnosis). While the cost-effectiveness of individual tests and testing strategies overlapped, CMA was consistently less cost-effective than WES and EP.

Conclusion: WES and EP are the most cost-effective genetic tests for epilepsy. Our analyses support, for a broad population of patients with unexplained epilepsy, starting with these tests. Although less expensive, CMA has lower yield, and its use as the first-tier test is thus not supported from a cost-effectiveness perspective.