Salzman 1999.

Methods	Design: multicentre, randomised, open label, parallel group study. For participants receiving non opioid therapy, dosing regimen stabilised ≥ 1 week before initiation of study medication and remained stable for the duration of the study Duration: up to 21 days Setting: outpatient
Participants	Stable cancer pain not adequately controlled by previous analgesic therapy with or without opioids N = 48, 35 completed titration period M 21, F 27 Mean age 61 years (range 25 ‐ 91)
Interventions	Oxycodone CR 12‐hourly, n = 24 Oxycodone IR 6‐hourly, n = 24 Starting dose for opioid‐naive patients = 20 mg/day, and for non‐opioid‐naive patients the starting dose was based on the prior 3 days of analgesic therapy. Titrated to maximum 400 mg daily to achieve PI ≤ 'slight' (1.5) for 48 h with ≤ 2 doses of rescue medication Stable non opioid medication continued, no other opioids allowed Rescue medication: oxycodone IR 5 mg, 10 mg, or 1/6 total dose, depending on daily dose, and taken no more than once every 4 hours
Outcomes	PI: 4‐point categorical scale, daily Adverse events: 4‐point categorical scale, daily Time to stable pain control: time to achieve PI ≤ 'slight' (1.5) for 48 h with ≤ 2 doses of rescue medication
Notes	Oxford Quality Score: R = 1, DB = 0, W = 1. Total = 2/5
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"randomized". Method used to generate sequence not clearly stated
Allocation concealment (selection bias)	Unclear risk	Method not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open label
Incomplete adverse event outcome data‐ patient level	Low risk	<90% participants included
Selective reporting bias for adverse events	High risk	Selective reporting. Treatment related AEs in >10% patients
Size	High risk	< 50 participants per treatment arm