CIBA 1988.

Methods	Double‐blind RCT of parallel design, conducted in USA
Participants	556 participants (aged 18 to 84 years) who experienced at least 3 nights of nocturnal leg muscle cramps per week
Interventions	7‐day placebo washout period followed by 2 weeks of a quinine‐vitamin E combination (259.2 mg quinine sulphate and 1600 IU vitamin E daily) or quinine sulphate 259.2 mg alone or vitamin E (1600 IU) alone, or placebo
Outcomes	Cramp number, cramp days, cramp intensity, cramp duration, sleep disturbance, adverse events
Notes	Large multicentre trial. Approximately double number of women than men across all treatment groups. Unpublished
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "...according to a predetermined randomized schedule"
Allocation concealment (selection bias)	Unclear risk	No details are given regarding how allocation may have been concealed
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "All capsules will be identical in appearance", "...weeks 2 and 3 will be double‐blind treatment periods" Comment: probably adequate
Incomplete outcome data (attrition bias) All outcomes	Low risk	All withdrawals and those lost to follow up accounted for, and intention‐to‐treat analysis performed
Selective reporting (reporting bias)	Low risk	All outcomes reported in detail
Other bias	Unclear risk	Conducted by manufacturer of quinine tablets