Elger 2010

Methods	Randomised, double‐blind, placebo‐controlled, parallel‐group multi‐centre study. Number of control centres: not reported. Country/location: Germany and US. 5 treatment arms: rufinamide 200 mg/day, 400 mg/day, 800 mg/day and 1600 mg/day, and placebo.
Participants	Participants: adolescents and adults aged 15‐65 years with refractory focal seizures. Gender: 54% males. Mean age (years): 36.1 (rufinamide all doses group 35.8; placebo group 37.3). Mean weight (kg): 72.2 (rufinamide all doses group 71.8; placebo group 74.0). Ethnic groups: not reported. Median number of focal seizures: rufinamide all doses group 11.4; placebo group 11.7. Duration of epilepsy: not reported. Inclusion criteria: inpatients or outpatients, aged 15‐65 years, who had a diagnosis of focal seizures, simple or complex (or both), with or without secondary generalisation, who were receiving stable dosages of 1‐3 AEDs for at least 4 weeks prior to starting the baseline phase and were experiencing ≥ 4 seizures per month during the 6 months prior to the baseline phase. Exclusion criteria: positive pregnancy test, lactation, use of oral/hormonal contraceptives, history of any seizure type other than focal seizure, status epilepticus within 24 months prior to study entry, any degenerative neurological disorder or history of a major psychiatric disorder within 24 months prior to study entry, or a history of suicide attempts or ideation; in addition, clinically relevant abnormalities in screening physical examination or laboratory data; presence of AIDS, acute hepatitis or other clinically relevant medical disorders; alcohol or drug abuse within 12 months prior to study entry; or the use of ethosuximide or felbamate. Comorbidities: none. Comedications: ≤ 3 AEDs. Total people randomised 647: rufinamide 200 mg/day group 127, rufinamide 400 mg/day group 125, rufinamide 800 mg/day group 129, rufinamide 1600 mg/day group 133, and placebo group 133. All participants included in analysis. 93 people withdrew from study: rufinamide 200 mg/day group 16; rufinamide 400 mg/day group 20; rufinamide 800 mg/day group 19; rufinamide 1600 mg/day group 21; and placebo group 17.
Interventions	Intervention: rufinamide 200 mg/day, rufinamide 400 mg/day, rufinamide 400 mg/day, rufinamide 1600 mg/day. Control: placebo. 2‐phase study: 12‐week baseline phase and 12‐week treatment phase.
Outcomes	Primary outcomes (as stated in the publication): mean % reduction in total focal seizures frequency per 28 days. Secondary outcomes (as stated in the publication): % responders (50%); adverse effects.
Notes	Stated aim of study: "This randomized trial was conducted to evaluate efficacy, safety, tolerability (seizure control and adverse effects) and pharmacokinetics of rufinamide as adjunctive treatment for refractory focal seizures." Language of publication: English. Commercial funding: yes. Publication status (peer review journal): yes. Publication status (journal supplement): no. Publication status (abstract): no. Funded by Eisai Inc. No conflict of interest. Elger 2005 (Epilepsia), Elger 2006 (Epilepsia) and Stefan 2000 (Epilepsia) are linked to this study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation scheme using block size of 5.
Allocation concealment (selection bias)	Low risk	Allocated participants to each of the 5 treatment groups in a 1:1:1:1:1 ratio.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No details for blinding of participants and personnel.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Details of outcome assessment blinding not provided. Identical medication with different dosages.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Analysed on ITT basis.
Selective reporting (reporting bias)	Low risk	Data published in full according to protocol.
Other bias	High risk	Sponsored by Eisai Inc., the manufacturer of rufinamide.