Summary of findings for the main comparison. Iron compared to placebo for the treatment of restless legs syndrome.

Iron compared to placebo for the treatment of restless legs syndrome
Patient or population: people with restless legs syndrome Settings: outpatient clinics Intervention: iron Comparison: placebo
Outcomes	№ of participants (studies) Follow up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects* (95% CI)
				Placebo	Difference with iron compared to placebo
Change in IRLS severity scale score	345 (7 RCTs)	⊕⊕⊕⊝ Moderate a	‐	The average reduction in IRLS severity scores in the placebo group ranged from 0.8 points to 12 points	The reduction in IRLS severity scores was 3.78 points (1.31 to 6.25) lower in the iron group than in the placebo group
Change in any measure of restlessness	370 (8 RCTs)	⊕⊕⊕⊝ Moderate a	‐	The amount of restlessness in the iron group was on average 0.74 SDs (0.23 to 1.26) less than in the placebo group
Quality of life (dichotomous measure)	39 (2 RCTs)	⊕⊝⊝⊝ Very low a b c	RR 2.01 (0.54 to 7.45)	Study population
				450 per 1000 reported an improvement in quality of life	454 more per 1000 (207 fewer to 2903 more)
Change in quality of life (continuous measure)	128 (3 RCTs)	⊕⊝⊝⊝ Very low a b c	‐	The improvement in quality of life in the iron group was on average 0.51 SDs (0.15 to 0.87) higher than in the placebo group
Withdrew to use other RLS medication or because of inadequate RLS symptom control	391 (9 RCTs)	⊕⊕⊝⊝ Low a c	RR 0.77 (0.41 to 1.47)	Study population
				195 per 1000	45 fewer per 1000 (115 fewer to 92 more)
Adverse events	298 (6 RCTs)	⊕⊕⊕⊝ Moderate a	RR 1.48 (0.97 to 2.25)	Study population
				260 per 1000	125 more per 1000 (8 fewer to 325 more)
Drop out due to adverse event	398 (9 RCTs)	⊕⊕⊝⊝ Low a c	RR 1.91 (0.50 to 7.26)	Study population
				16 per 1000	14 more per 1000 (8 fewer to 98 more)
*The risk in the intervention group (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; IRLS: International Restless Legs Scale; RCT: randomised controlled trial; RR: risk ratio; SD: standard deviation
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect

^a We downgraded one level for publication bias for several reasons: 1) one study completed in 2012 (NCT00685815) for which published results could not be found in the search; 2) generally small sample sizes; and 3) the majority of participants were in trials funded by pharmaceutical companies.
 ^bWe downgraded one level for the possibility of selective outcome reporting, as this outcome was infrequently reported across studies.
 ^cWe downgraded one level because the Optimal Information Size (OIS) calculation suggests insufficient power for this outcome.