Graf 2005Low.

Methods	Randomised, double‐blind, placebo‐controlled trial with parallel group design.
Participants	Country: Germany. Number of participants randomised: 160, 104 males and 56 females, mean age 58 years with probable or definite amyotrophic lateral sclerosis (ALS). Inclusion criteria: patients with probable or definite amyotrophic lateral sclerosis (ALS) treated with riluzole and disease duration of less than 5 years. Exclusion criteria: none stated.
Interventions	Patients were randomly assigned to receive: group 1: vitamin E (alpha‐tocopherol), 5000 mg (five times daily one capsule of 1000 mg) (n = 83); group 2: placebo (n = 77); for a period of 18 months.
Outcomes	Primary outcome measure was: survival, calculating time to death, tracheostomy, or permanent assisted ventilation. Secondary outcome measures were: the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing, spasticity scale, ventilatory function and the Sickness Impact Profile. Additional information obtained through personal communication with authors.
Notes	Compliance with treatment was checked by measuring the plasma vitamin E levels. Vitamin plasma levels were, as expected, significantly higher in the high dose vitamin E group than in the placebo group. There were no losses to follow‐up. Trial agents were provided by Schwarzhaupt, Cologne, Germany. Additional information obtained with personal communication with authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sequence generation was achieved using computer random number generation.
Allocation concealment (selection bias)	Low risk	Allocation was controlled by a central and independent randomisation unit, so that intervention allocations could not have been foreseen in advance of, or during, enrolment.
Blinding (performance bias and detection bias) All outcomes	Low risk	The trial was described as blinded, the parties that were blinded, and the method of blinding was described, so that knowledge of allocation was adequately prevented during the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	The numbers and reasons for dropouts and withdrawals in all intervention groups were described.
Selective reporting (reporting bias)	Low risk	Pre‐defined, or clinically relevant and reasonably expected outcomes are reported on.
Other bias	Low risk	The trial appears to be free of other components that could put it at risk of bias.