Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report by the manufacturer (UCB Japan Co. Ltd.) on the additional benefits and cost-effectiveness of brivaracetam in patients with uncontrolled focal-onset seizures. This report summarizes the ATAG review and reanalysis. The target population was divided into two groups: (a) patients receiving monotherapy, (b) patients receiving combination therapy. The comparator technology was levetiracetam for population (a) and levetiracetam + drug therapy for population (b). The technology under evaluation was brivaracetam for population (a) and brivaracetam + drug therapy for population (b). For evaluating additional effectiveness, the systematic review (SR) conducted by the manufacturer for population (a) identified no randomized controlled trials (RCTs) directly comparing brivaracetam and levetiracetam. No SR was conducted for non-RCTs. As a result, for population (a), it was determined that no trials of sufficient quality existed for evaluation, and thus no additional benefit could be drawn. For population (b), seven studies were identified to examine the additional benefit of combination therapy with brivaracetam, although no RCTs directly comparing brivaracetam + drug therapy and levetiracetam + drug therapy were identified. Furthermore, the manufacturer conducted a frequentist network meta-analysis (NMA) after performing literature selection and outcome extraction based on prior studies and applying continuity correction to data with zero events. The manufacturer concluded that additional benefit was demonstrated based on the point estimates for the complete seizure freedom rate and treatment discontinuation rate due to adverse events. ATAG conducted an independent SR and determined that there were no RCTs or appropriate non-RCTs for evaluating additional effectiveness for population (a). ATAG determined that for population (b), additional benefit was demonstrated for "treatment discontinuation due to adverse events", while clear evidence demonstrating additional benefit for "seizure suppression" was lacking. Thus, ATAG considered it appropriate to conduct a costeffectiveness analysis for population (b) and examined the analysis provided by the manufacturer. The manufacturer conducted a cost-effectiveness analysis for population (b) by constructing a Markov model to evaluate the cost-effectiveness of brivaracetam + drug therapy. ATAG identified several methodological issues with the analysis performed by the manufacturer and conducted a reanalysis. First, ATAG conducted a reanalysis assuming that treatment effects on seizure suppression were null (OR=1.000). Second, the manufacturer estimated a higher treatment continuation rate for brivaracetam + drug therapy by directly comparing data obtained from RCTs and observational studies. In the ATAG assessment, the treatment continuation rate for brivaracetam + drug therapy was estimated by multiplying the treatment discontinuation rate of levetiracetam + drug therapy by the treatment effect on "treatment discontinuation due to adverse events". Third, while the manufacturer modeled the "posttreatment" state as equivalent to 'death', ATAG judged this approach to be inappropriate and applied the costs and QOL values for "non-responders". Fourth, ATAG conducted a reanalysis using QOL values obtained directly from patients in the clinical trials (N01252, N01253, and N01254 trials). The reanalysis showed that, compared to levetiracetam + drug therapy, brivaracetam + drug therapy had an incremental cost of JPY 1,099,134 and 0.023 QALYs gained in population (b), with an incremental cost-effectiveness ratio (ICER) of JPY 48,163,534/QALY. In conclusion, these results suggest that the ICER for brivaracetam compared to the comparator is likely to belong to the "more than JPY 10 million/ QALY" interval for population (b), from the perspective of public healthcare payers in Japan.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2026

URL for published report: https://c2h.niph.go.jp/en/results/C2H2405.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com