Heiskanen 1997.

Methods	Design: Randomised, double‐blind (double dummy), two‐phase cross‐over study. Prestudy open label titration phase (maximum 21 days) to achieve effective pain relief with acceptable adverse effects for ≥ 48 hours Duration: 2 x 3 ‐ 6 days + titration phase up to 21 days Setting: Not stated
Participants	Chronic cancer pain requiring opioid analgesics N = 45 (27 analysed) M 16, F 11 Mean age 60 years (range 39 ‐ 76)
Interventions	Oxycodone CR + morphine‐matched placebo, assumed 12‐hourly Morphine CR + oxycodone‐matched placebo, assumed 12‐hourly Dose adjustment allowed Rescue medication: Oxycodone IR or MIR in a dose of approximately 1/6 to 1/8 of the daily dose of controlled‐release formulation Stable NSAIDs continued at the same dose
Outcomes	PI: 4‐point VRS (none, slight, moderate, severe) x 4 daily Acceptability of therapy: 5‐point VRS (very poor, poor, fair, good, excellent) x 2 daily Adverse events Modified Specific Drug Effect Questionnaire: participants and investigator, at end of study
Notes	Oxford Quality Score: R = 2, DB = 2, W = 1. Total = 5/5
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Computer generated randomisation for the open‐label titration phase and again for the double‐blind phase was performed by the Purdue Frederick Company and a list of randomisation codes was kept by the hospital pharmacist"
Allocation concealment (selection bias)	Low risk	"list of randomisation codes was kept by the hospital pharmacy". Probably adequate
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double dummy method, "matched placebo tablets"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double dummy method, "matched placebo tablets"
Incomplete adverse event outcome data‐ patient level	High risk	AEs reported on fewer than 90% participants
Selective reporting bias for adverse events	Low risk	Appears to be a complete list
Size	High risk	< 50 participants per treatment arm