Diener 2005.

Methods	Multicentre, randomised, double‐blind, placebo‐controlled, parallel‐group study. Participants treated 2 headache episodes, each with a single oral dose administered when pain at least mild (≥ 30 mm on 100 mm VAS) Duration: 4 h, with assessments at baseline, 0.5, 1, 2, 3, and 4 h post dose
Participants	Episodic tension‐type headache (13%) or migraine with or without aura (84%) ‐ in accordance with IHS criteria, with a history of ≥ 12 months and ≥ 2 headache episodes in previous 3 months Participants were excluded if they: treated headaches with prescription analgesics or migraine drugs, required higher single doses of non‐prescription analgesics than indicated in the patient information leaflet, normally treated headaches with non‐prescription analgesics in effervescent tablet form, had > 10 days of headache per month, suffered possible menstrual migraine, or whose headaches normally spontaneously resolved within 4 h Participants aged 18 to 65 years N = 1889 (1743 for efficacy) M 453, F 1436 Mean age not reported Mean baseline pain intensity 64 mm on 100 mm VAS
Interventions	Aspirin 500 mg + paracetamol 400 mg + caffeine 100 mg, n = 521 (482 for efficacy) Aspirin 500 mg + paracetamol 400 mg, n = 538 (498 for efficacy) Aspirin 1000 mg, n = 276 (252 for efficacy) Paracetamol 1000 mg, n = 275 (251 for efficacy) Caffeine 100 mg, n = 141 (132 for efficacy) Placebo, n = 138 (128 for efficacy) No concomitant treatment with prescription or non‐prescription analgesics, antidepressants, or antipsychotic medication, or migraine prophylaxis
Outcomes	PI: 100 mm VAS PGE: 4‐point scale ('very good', 'good', 'less good', 'poor') Withdrawals and dropouts Serious adverse events
Notes	Oxford Quality Score: R2, DB2, W1. Total = 5/5
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation list
Allocation concealment (selection bias)	Low risk	Consecutive participants assigned in sequential order
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Medication was "identical in colour, size, shape and taste"
Size	Low risk	> 200 participants in relevant treatment arms