Moore 2015c.

Methods	Multicentre, RCT, DB (double‐dummy), placebo‐controlled and active comparator, 10 parallel groups. Medication administered within 4 h of surgery when PI ≥ 40/100 and 4‐point VRS ≥ 2. Pain assessed at 0, 15, 30, 45 min, and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 h.
Participants	Outpatient surgical removal, under local anaesthesia, of ≥ 1 third molar (≥ fully or partially impacted in mandibular bone). N = 606 for efficacy, 611 for safety. M 247, F 359. Mean age: 27 years (range 18 to 64). Baseline PI: 64% moderate, 35% severe (3 mild, 2 missing data).
Interventions	Dexketoprofen 12.5 mg, n = 60. Dexketoprofen 25 mg, n = 60. Tramadol 37.5 mg, n = 59. Tramadol 75 mg, n = 59. Dexketoprofen 12.5 mg + tramadol 37.5 mg, n = 60. Dexketoprofen 12.5 mg + tramadol 75 mg, n = 62. Dexketoprofen 25 mg + tramadol 37.5 mg, n = 63. Dexketoprofen 25 mg + tramadol 75 mg, n = 61. Ibuprofen 400 mg, n = 60. Placebo, n = 62.
Outcomes	PI: standard 4‐point VRS (0 = none, 3 = severe). PR: standard 5‐point VRS (0 = none, 4 = complete). PGE: standard 5‐point VRS (1 = poor, 5 = excellent) at 24 h or use of rescue medication/withdrawal. Use of rescue medication. Time to use of rescue medication.
Notes	Oxford Quality Score: R2, DB2, W1. Rescue medication: paracetamol 1000 mg (maximum 4 doses in 24 h) after ≥ 1 h.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"computer‐generated" "blocked randomisation procedure, with block size of 10".
Allocation concealment (selection bias)	Low risk	"Interactive Voice/Web Response (IVR/IWR) system".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"double‐dummy design".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"double‐dummy design".
Size	Unclear risk	50‐199 participants per treatment arm (range 59 to 63).