title: A systematic review of trial methodology, using the placebo groups of randomized controlled trials in paediatric postoperative pain.
abstract: Trial methodology was evaluated in paediatric analgesic studies. Databases were searched for randomised, placebo controlled studies of systemic paracetamol, NSAIDs and opioids administered for acute postoperative pain in children. Eighty-three studies met the inclusion criteria and 40 were included for the analysis. Analgesics were administered for established postoperative pain in two studies only. In all other studies they were administered in a prophylactic manner. As study design and sensitivity are particularly demanding in studies using pre-emptive dosing of analgesics, the placebo groups were analysed for issues of study sensitivity. Postoperative pain outcomes included pain scores in 34, rescue analgesia in 36, time to first rescue analgesia in 15, pain on activity in eight, number of patients with pain in six, pain relief in three, global efficacy rating in two and analgesic consumption via PCA in four studies. Twenty of 36 studies reported criteria for rescue analgesia that varied from 20 to 77% of the maximum pain intensity. Need of rescue analgesia showed more often differences between study groups than time to first rescue analgesia or pain intensity. Rescue analgesia was administered to 21-100% of the patients in the placebo groups where no other analgesics were given perioperatively. Most patients in the placebo groups had pain that was greater than 30% of the maximum. In conclusion, analysis of the methodology showed several aspects of trial design that can be improved in future studies. Placebo control groups can be used in paediatric analgesic studies to demonstrate internal sensitivity.
authors.affiliation: Pain Clinic, Department of Anaesthesia and Intensive Care Medicine, Helsinki University Central Hospital, P.O. Box 140, FIN-00029 HUS, Finland. katri.hamunen@hus.fi
authors.forename: Katri
authors.initials: K
authors.lastname: Hamunen
authors.forename: Eija
authors.initials: E
authors.lastname: Kalso
mesh_terms: D016058:Analgesia, Patient-Controlled; D000700:Analgesics / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy*; D010919:Placebos / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D010919:Placebos