Hay 2008

Methods	Study design: individually‐randomized, blinded three‐arm trial. Study dates and duration: January 2005 to May 2007. Method of temperature measurement: axillary continuous probe for 24 hours, then standard digital axillary thermometer for home measurements. Time points measured in study: temperature taken every 30 seconds using axillary temperature probe for first 24 hours, then as needed with standard axillary thermometer at home.
Participants	Number: 156 randomized. Number of patients in each intervention: paracetamol n=52, ibuprofen n=52, paracetamol plus Ibuprofen n=52. Inclusion criteria: children aged 6 months to 6 years in the primary care setting and households in England. Required axillary temperatures of at least 37.8 °C and up to 41 °C. Exclusion criteria: if patients required hospital admission, clinically dehydrated; had recently participated in another trial; had previously participated in PITCH; had a known intolerance, allergy or contraindication to a trial drug; had a chronic neurological, cardiac, pulmonary (except asthma), liver or renal disease; or had parents who could not read or write in English. Baseline characteristics: Sex, N(%): paracetamol (n=52) – boy = 26 (50), girl = 26 (50), ibuprofen (n=52) – boy = 37 (71), girl = 15 (29), both (n=52) – boy = 25 (48), girl = 27 (52). Diagnoses included otitis media, respiratory tract infections, non‐specific viral illnesses etc.
Interventions	Group A: paracetamol 15 mg/kg every 4‐6 hours Group B: ibuprofen 10 mg/kg every 6‐8 hours Group C: paracetamol + ibuprofen alternating Advice was given to parents to give the study drugs for up to 48 hours
Outcomes	Primary: Number of minutes without fever (<37.2 °C) in the first 4 hours The proportion of children reported as being normal on the discomfort scale at 48 hours Secondary: Time to temperature first falling below 37.2 °C in the first 24 hours (fever clearance) The time spent without fever over 24 hours Proportion of children without fever associated symptoms: discomfort, reduced activity, reduced appetite and disturbed sleep at 48 hours and day 5 Adverse effects
Notes	Location: England Setting: multi‐centre – 35 primary care sites (NHS Direct, one walk‐in centre, 30 general practices, two general practitioner out of hours cooperatives, and the emergency department of the Bristol Royal Hospital for Children) and households. Funding: National Institute for Health Research Health Technology Programme.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization sequence was generated via a remote, automated telephone service provided by the Health Services Research Unit at the University of Aberdeen.
Allocation concealment (selection bias)	Low risk	After written informed consent had been obtained and the baseline questionnaire completed, the research nurse telephoned a remote, automated randomization service.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Study medication identity was concealed.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Research nurse was blinded to process.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Article did not address why three patients (one from ibuprofen and two from ibuprofen plus paracetamol group) had missing data for time without fever. "Attrition was minimal." "Thus, children were omitted from analyses only if none of the data required were available, and as these were so few in number the influence of missing data on the intention‐to‐treat analyses was negligible."
Selective reporting (reporting bias)	Low risk	All assessed outcomes were reported.
Other bias	Low risk	The possibility of receiving either or both drugs combined and the severity of the child's illness may have influenced parental decision to participate.