OBJECTIVES: Diagnosis of rare genetic childhood epilepsy is a major challenge. Diagnostic delay is estimated at 3-6 years and over 50% of patients remain without a definitive molecular diagnosis. Whole-genome sequencing (WGS) has improved the chances of molecular diagnosis, and it has a higher yield than whole-exome sequencing (WES), gene panels and chromosomal microarray (CMA). While the high cost limits adoption, WGS may be more cost-effective if applied early to shorten the diagnostic pathway. This study assessed the cost-effectiveness of early diagnostic WGS in children aged under five years with suspected rare genetic epilepsy in the UK National Health Service (NHS).

METHODS: A de novo cost-effectiveness model with 5-year time horizon was constructed comprising a decision tree and a Markov model. Two diagnostic approaches were compared in a hypothetical cohort of patients: 1) WGS replaced all other genetic/genomic tests in Year 1 (“early WGS”); 2) CMA+WES were carried out in Year 1 and for those without a definitive diagnosis a 4-year delay was assumed with WGS (“late WGS”). Diagnostic yield, probabilities of achieving adequately controlled epilepsy, healthcare resource utilization (HCRU), and unit costs were extracted from public sources. An incremental cost effectiveness ratio (ICER) was calculated as additional cost per additional molecular diagnosis in Year 1, and per life years gained (LYG) over five years.

RESULTS: In Year 1, WGS incurred £1,341 incremental cost, 5% higher proportion of diagnoses, and ICER of £26,938 per additional diagnosis compared to CMA+WES. Over five years, early WGS incurred lower HCRU, £5,740 cost savings and 0.001 higher LYG compared to CMA+WES and late WGS.

CONCLUSIONS: The higher cost of WGS impedes its adoption, but 5-year cost-effectiveness results suggested good value for money when WGS is performed as the first genetic/genomic test.