Manjunatha 2009

Methods	Double‐blind randomised controlled trial. Study was conducted from 2003 to 2005 at Wishaw General Hospital, Lanarkshire, UK
Participants	Infants who satisfied the criteria for ROP screening (≤ 31 weeks PMA, or ≤ 1.5 kg birth weight) were recruited into the study. Infants who were on morphine or paracetamol for other reasons, breast‐fed infants whose mothers were on methadone or other analgesics and infants with gastrointestinal problems such as ileostomy/colostomy were excluded
Interventions	Neonates (n = 18) were randomly assigned to receive a single oral dose of morphine sulphate 200 μg/kg (n = 6) or paracetamol 20 mg/kg (n = 6) or placebo (n = 6)
Outcomes	PIPP – The infant’s face, saturation monitor and time frame cards were recorded on videotape over a 1 to 2 minute period, at 5 minutes before, then at 5 minutes, 30 minutes, 1 hour, 2 hours and 3 hours after the procedure. 2 separate individuals subsequently scored the information independently. Main outcome was PIPP scores 5 minutes after ROP screening
Notes	Dr Manjunatha and Ms Hazel Fisher (Senior Pharmacist) volunteered, "The 3 solutions looked identical (clear, colourless solutions). The diluent for all 3 solutions was hydroxybenzoate, with the placebo being made up with preserved water"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The random sequence was generated by the pharmacist by pulling folded tickets out of a bag with morphine, paracetamol or placebo on the tickets. Equal numbers of tickets were provided in the bag for each arm and all tickets were allocated
Allocation concealment (selection bias)	Low risk	Blinded random assignment was done by picking up consecutive envelopes
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The pharmacy department at Wishaw General Hospital supplied trial substances. Infants received the trial substance (placebo or medication) 1 hour before the procedure was performed. The dose of each trial substance was dispensed as 10 mL and was administered as 2 mL/kg/dose, 1 hour before the procedure. The 3 solutions looked identical (clear, colourless solutions). The diluent for all 3 solutions was hydroxybenzoate, and the placebo was made up with preserved water
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The infant’s face, saturation monitor and time frame cards were recorded on videotape over a 1 to 2 minute period, at 5 minutes before, then at 5 minutes, 30 minutes, 1 hour, 2 hours and 3 hours after the procedure. 2 separate individuals subsequently scored the information independently
Incomplete outcome data (attrition bias) All outcomes	Low risk	18 infants were enrolled. At 5 minutes post eye examination, the PIPP score was not reported for 1 infant in the paracetamol group
Selective reporting (reporting bias)	Unclear risk	The protocol for the study was available to us. No selective outcome reporting is apparent. However only 18 infants from a preset sample of 63 were enrolled
Other bias	Low risk	Study appears free of other bias