Leppik 1991

Methods	Randomised, double‐blind, placebo‐controlled, cross‐over study 2 treatment sequences: felbamate‐placebo and placebo‐felbamate 8 to 10‐day titration period and 10‐week treatment period with 3‐week wash‐out period
Participants	The Epilepsy Research Center, University of Minnesota (UMN) and the University of Virginia Health Sciences Center (UVA). A total of 59 participants were randomised, aged 18‐55 years. 56 participants (32 male) completed the trial. 31 participants were randomised to felbamate‐placebo sequence and 28 to placebo‐felbamate. Mean 8‐weekly baseline seizure frequencies of the 56 participants who completed the trial: UMN: felbamate‐placebo group = 43.6, placebo‐felbamate group = 42.8 UVA: felbamate‐placebo group = 28.9, placebo‐felbamate group = 44.0 Other AEDs were phenytoin and carbamazepine Simple partial seizures, complex partial seizures, secondary generalised seizures
Interventions	Add‐on placebo or felbamate In the initial 8 to 10‐day treatment, the dosage was increased daily to 3000 mg/d. Due to reports of nausea and vomiting, the dosage was reduced to 2600 mg/d. The mean felbamate dosage was 2300 mg/d
Outcomes	Seizure frequency reduction (SFR) Seizure frequency percentage reduction (SFPR) Truncated seizure frequency percentage reduction (TSFPR) Adverse effects
Notes	Of the 59 participants randomised, 3 dropped out. 2 of them completed the placebo period, and the 3rd did not begin the placebo period. All 3 received felbamate treatment for short periods. The primary efficacy analyses, such as SFR, SFPR, TSFPR (TSFPR = SFPR except that SFPR values less than ‐ 100 are truncated to ‐ 100), were based on 56 participants who completed both treatment periods. Adverse effects were analysed based on 59 participants randomised.
Risk of bias
Bias	Authors' judgement	Support for judgement
Selective reporting (reporting bias)	Low risk	The outcomes mentioned in the methods were reported.
Random sequence generation (selection bias)	Unclear risk	Quote: "...randomised ... clinical trial. Table 1 summarizes the baseline characteristics of these 56 patients by center and randomised treatment sequence." Comment: not stated how random sequence generated
Allocation concealment (selection bias)	Unclear risk	There was no description of allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "...double‐blind treatment periods. ...All medications were pre‐packed under the supervision of the unblinded pharmacist." Comment: probably not done
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	There was no description.
Incomplete outcome data (attrition bias) All outcomes	High risk	56/67 completed the trial