Pini 2008.

Methods	R, DB, PC, cross‐over trial 3 consecutive episodes treated with 3 different medications
Participants	Episodic TTH (IHS), 4‐14 days/month, no nausea, vomiting, photo‐ or phonophobia. Previous response to OTC medication. Daily consumption ≥ 2 cups of coffee Excl: contraindications to study medication; migraine or post‐traumatic headache; overuse of analgesics; significant medical history n = 99 (93 for safety, 81 for efficacy) M 40, F 59 Mean age 35 years (SD 10, range 19‐64 years) Baseline PI: 59% mod, 16% mild, 25% severe
Interventions	Paracetamol 1000 mg + caffeine 130 mg Naproxen sodium 550 mg Placebo Rescue medication (ibuprofen 600 mg) to be taken at 2 h if necessary
Outcomes	PI: 4‐point scale over 4 h PR: 5‐point scale over 4 h Rescue medication Patient global evaluation: 5‐point scale at 4 h Use of rescue medication AEs
Notes	Oxford Quality Score: R2, DB2, W1
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomisation code"
Allocation concealment (selection bias)	Low risk	"Assigned in sequential order of entry"; "access to the randomization code was strictly controlled and treatment assignment remained unknown to all parties until formal database lock"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"double‐dummy method"; "identical boxes"; "matched supplies, identical in colour, size, shape and taste"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"double‐dummy method"; "identical boxes"; "matched supplies, identical in colour, size, shape and taste"
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT analysis included only those taking all 3 interventions. LOCF imputation. 10 participants did not provide pain relief data, with no reason given
Size	Unclear risk	50‐200 participants per treatment arm (94‐98)