Klepstad 2003.

Methods	Design: randomised, double blind (double dummy), parallel group study. Initial dose 60 mg morphine per day, then titrated to pain relief; study stopped 2 days after achieving stable analgesic dose (≤3 on 7‐point pain VRS and ≤ 2 doses of rescue medication) Setting: hospital
Participants	Malignant disease with pain despite treatment with weak opioids for mild to moderate pain N = 40 (36 started the titration phase) Age 57 to 71
Interventions	Mm/r 24 h release, with dummy tablets given to Mm/r group for additional doses MIR 4‐hourly No other opioids allowed, but NSAIDs continued Rescue medication: ketobemidone
Outcomes	PI: VAS Participant satisfaction: 5‐point VRS Use of rescue medication Adverse events: nausea, loss of sleep, tiredness, loss of appetite, constipation, vertigo: 4‐point categorical scale QoL: EORTC QLQ‐C30
Notes	NB Data in section 3.4 of paper are incorrect (typo); Table 4 correct ‐ confirmed with author 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	"hospital pharmacy performed a computerised randomisation"
Allocation concealment (selection bias)	Low risk	"none of the pharmacists arranging the study drugs were involved in other parts of the study"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"double blind, double dummy" "placebo tablets identical in appearance and taste"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"double blind, double dummy" "placebo tablets identical in appearance and taste"
Incomplete adverse event outcome data‐ patient level	Unclear risk	Cannot tell what the denominator is
Selective reporting bias for adverse events	High risk	mean intensity of 6 AEs reported
Size	High risk	< 50 participants per treatment arm