Bill 1997

Methods	Multicentre, double‐blind, parallel‐group trial conducted in centres in Argentina, Brazil, Mexico, South Africa 2 treatment arms: OXC and PHT
Participants	Participants aged 16‐65 years with newly diagnosed epilepsy with partial or generalised tonic clonic seizures A minimum of 2 seizures, separated by at least 48 h, within 6 months preceding trial entry No previous AED, except emergency treatment of seizures for a maximum of 3 weeks prior to trial entry Number randomised: total = 287, OXC = 143, PHT = 144 174 male participants (61%); 182 participants with partial epilepsy (63%) Mean age (range) = 26 (15‐91) years
Interventions	Monotherapy with OXC or PHT 8‐week titration period started with 300 mg OXC or 100 mg PHT, increased bi‐weekly, based on clinical response After 8 weeks participants were to be on a three‐times‐a‐day regimen with daily doses of 450 mg‐2400 mg OXC or 150 mg‐800 mg PHT Continued during 48‐week maintenance with adjustment according to clinical response A third long‐term, open‐label extension phase followed the maintenance period. Double‐blind results only were reported Range of follow‐up = 0‐19 months
Outcomes	The proportion of seizure‐free participants who had at least one seizure during the maintenance period Time to premature discontinuation due to adverse experiences Rate of premature discontinuations for any reason Overall assessments of efficacy and tolerability and therapeutic effect Individual adverse experiences Laboratory values Seizure frequency during maintenance
Notes	IPD provided for all outcomes of this review from trial sponsor Novartis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Treatment groups randomised in 1:1 ratio across centres via computer‐generated randomisation numbers over balanced blocks of size 6
Allocation concealment (selection bias)	Low risk	Allocation concealment was achieved with sequentially‐numbered packages that were identical and contained identical tablets (information provided by trial statistician)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Trial conducted in 2 phases: 56‐week, double‐blind phase followed by long‐term, open‐label extension. Double‐blind phase results reported only. Blind achieved with divisible OXC and PHT tablets identical in appearance
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rates reported in both treatment phases, participants withdrawing from treatment were no longer followed up so seizure outcomes had to be censored at time of withdrawal and therefore analyses for remission and seizure outcomes could not adopt an ITT approach
Selective reporting (reporting bias)	Low risk	All outcomes reported or calculated with IPD provided (see footnote 2)
Other bias	Low risk	None identified