Lipton 2009 Study 2.

Study characteristics
Methods	Multicentre, R, DB, PC, cross‐over. Single dose per attack. 4 attacks treated: all with active or 3 active and 1 placebo (in random order). Washout between attacks not specified, but all headache medications prohibited within 24 h of a treated attack, and AE data collected for 72 h after treatment Medication taken within 1 h of onset when PI was mild Assessments at 0, 2, 4, 24 h
Participants	Migraine ± aura (IHS 2004), aged 18 to 65 years. History ≥ 6 months with frequency of 2 to 6 attacks per month and untreated severity ≥ moderate and identifiable mild phase Excluded: uncontrolled hypertension, cardio‐ or cerebrovascular disease N = 565 (563 for efficacy) F = 90% Mean age 41 years
Interventions	Sumatriptan plus naproxen 85/500 mg (1678 attacks treated) Placebo (422 attacks treated) 5 treatment groups with different medication sequences (Nap: naproxen; P: placebo; Sum: sumatriptan) P, Sum/Nap, Sum/Nap, Sum/Nap; Sum/Nap, P, Sum/Nap, Sum/Nap; Sum/Nap, Sum/Nap, P, Sum/Nap; Sum/Nap, Sum/Nap, Sum/Nap, P; Sum/Nap, Sum/Nap, Sum/Nap, Sum/Nap Rescue medication allowed after 2 h if necessary (recommended 2 x 220 mg naproxen sodium with additional 1 x 220 mg 6 h later if needed)
Outcomes	Pain‐free at 2 h 24‐h sustained pain‐free Presence and relief of associated symptoms at 2 h Use of rescue medication AEs Withdrawals
Notes	Oxford Quality Score: R1, DB1, W1. Total = 3
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Drop‐outs described
Study size	Unclear risk	50 to 200 participants per treatment arm