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

OBJECTIVETo compare the cost-effectiveness of genetic testing strategies in patients with epilepsy of unknown etiology. METHODSThis meta-analysis and cost-effectiveness study compared strategies involving 3 genetic testschromosomal 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. RESULTSTwenty studies provided information on the diagnostic yield of CMA (8 studies), EP (9 studies), and WES (6 studies). The diagnostic yield was highest for WES0.45 (95% confidence interval [CI]0.33–0.57) (0.32 [95% CI0.22–0.44] adjusting for potential publication bias), followed by EP0.23 (95% CI0.18–0.29), and CMA0.08 (95% CI0.06–0.12). 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. CONCLUSIONWES 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.