for the main comparison.

Riluzole compared with placebo for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)
Patient or population: patients with ALS/MND Settings: large European and US ALS centers Intervention: riluzole Comparison: placebo
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Riluzole
Mortality or tracheostomy at 12 months (pooled hazard ratio)(riluzole 100 mg)	510 per 1000	419 per 1000 (367 to 475)	HR 0.83 (0.70 to 1.00)	1282 (3 studies)	++++ high	When the results of the third trial of older and more seriously affected patients were included, the results were still significant (P = 0.046). This relative effect represents a three month increase in median survival from 11.8 to 14.8 months
Per cent mortality at 12 months (riluzole 100 mg)	440 per 1000	343 per 1000 (286 to 405)	RR 0.78 (0.65 to 0.92)	799 (3 studies)	++++ high
Rate of decline of Norris Scale ‐ Norris Limb (riluzole 100 mg) Follow up: 12 months	23.1 per year weighted mean rate of decline	The mean rate of decline of Norris Scale ‐ Norris Limb in the intervention groups was 3.94 slower (7.25 to 0.64 slower)		731 (3 studies)	++++ high	Although the change in function was not significant in the individual studies, the pooled data show a slower decline of limb function in the treated group
Rate of decline of Norris Scale ‐ Norris Bulbar (riluzole 100 mg) Follow up: 12 months	11.1 per year weighted mean rate of decline	The mean rate of decline of Norris Scale ‐ Norris Bulbar in the intervention groups was 2.06 slower (3.86 to 0.27 slower)		742 (3 studies)	++++ high	Although the change in function was not significant in the individual studies, the pooled data show a slower decline of bulbar function in the treated group
Adverse event: nausea	91 per 1000	142 per 1000 (96 to 207)	RR 1.55 (1.06 to 2.28)	801 3 studies	++++ high
Adverse event: asthenia	116 per 1000	175 per 1000 (124 to 246)	RR 1.5 (1.07 to 2.12)	801 3 studies	++++ high
Adverse event: 3‐fold increase in alanine transferase	49 per 1000	129 per 1000 (78 to 211)	RR 2.62 (1.59 to 4.31)	801 3 studies	++++ high
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; HR: hazard ratio
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.