Cudkowicz 2003.

Methods	Randomized, double‐blind, placebo‐controlled
Participants	United States N = 296 (topiramate ‐ 197, placebo ‐ 97) Mean age: 57.8 (topiramate), 57.7 (placebo) Gender distribution, male (%): 63.5% (topiramate), 66% (placebo) Family history of ALS: 3.1% (topiramate), 6.2% (placebo)
Interventions	Topiramate or placebo Maximum tolerated dose of a maximum of 800 mg/day
Outcomes	Primary: change in the rate of decline of the arm megascore, calculated based on the results on MVIC testing of 8 arm muscles (bilateral shoulder and elbow, flexion and extension) Secondary: forced vital capacity, ALSFRS, grip strength, survival (death or tracheostomy)
Notes	Support from National Institute of Neurological Disorders and Stroke (NINDS), Muscular Dystrophy Association (MDA), Ortho‐McNeil Pharmaceutical Inc. and General Clinical Research Centers
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	Computer generated randomization
Allocation concealment?	Low risk	Coordination center staff, all site investigators, coordinators and the clinical evaluators were blind to treatment assignment throughout the study
Blinding? All outcomes	Low risk	Coordination center staff, all site investigators, coordinators and the clinical evaluators were blind to treatment assignment throughout the study
Incomplete outcome data addressed? All outcomes	Low risk	Based on the intention‐to‐treat principle, the data set for analysis included all randomized participants with the exception of two participants
Free of selective reporting?	Low risk	Results for all primary and secondary outcome measures reported (see Table 3 in original paper)
Free of other bias?	High risk	Relatively small number of familial ALS participants