Kaleida 1991.

Methods	Randomised ‐ yes, stratified randomisation, method of randomisation not described Concealment of allocation ‐ unclear, method not described Double‐blind ‐ yes, blinding procedure not described Intention‐to‐treat (ITT) ‐ yes Loss to follow‐up ‐ not described Design ‐ parallel
Participants	N ‐ 536 children (representing 1049 non‐severe acute otitis media (AOM) episodes; 980 non‐severe AOM episodes included for primary analysis) Age ‐ between 7 months and 12 years Setting ‐ secondary care: children's hospital and a private paediatric practice in Pittsburgh (USA) Inclusion criteria ‐ AOM based on presence of middle‐ear effusion, as determined otoscopically, in association with specified symptoms of acute middle‐ear infection (fever, otalgia or irritability), or signs of acute infection (erythema or white opacification, or both, accompanied by fullness or bulging and impaired mobility), or both Exclusion criteria ‐ children who recently received antibiotics, who had potential complicating or confounding conditions (e.g. eardrum perforation, asthma or chronic sinusitis) Baseline characteristics ‐ balanced
Interventions	Children were enrolled for a 1‐year period. At entry each child was assigned randomly to a treatment regimen that specified consistent treatments for episodes of non‐severe and severe AOM based on severity of otalgia and the presence of fever (> 39 °C orally or > 39.5 °C rectally within the 24‐hour period before presentation) Non‐severe AOM episodes were treated with: Tx ‐ amoxicillin 40 mg/kg/day 3 times daily for 14 days; N = 522 (N = 488 included in primary analysis) C ‐ placebo for 14 days; N = 527 (N = 492 included in primary analysis) Severe AOM episodes in children aged < 2 years were treated with: Tx 1 ‐ amoxicillin 40 mg/kg/day 3 times daily for 14 days Tx 2 ‐ amoxicillin 40 mg/kg/day 3 times daily for 14 days and myringotomy Severe AOM episodes in children aged ≥ 2 years were treated with: Tx 1 ‐ amoxicillin 40 mg/kg/day 3 times daily for 14 days Tx 2 ‐ amoxicillin 40 mg/kg/day 3 times daily for 14 days and myringotomy Tx 3 ‐ placebo and myringotomy
Outcomes	Primary outcome ‐ initial treatment failure: in non‐severe episodes this was the case when either otalgia, fever or both was present more than 24 hours after treatment was initiated and when 48 hours or more after initial treatment was initiated the child's temperature reached 38 °C orally or 38.5 °C rectally or an otalgia score of ≥ 6 was present Secondary outcomes ‐ (a) recurrent AOM defined as the development of AOM 15 days or more after the initiation of treatment for a preceding episode, (b) new episodes of otitis media with effusion defined by otoscopy and tympanometry findings After initial visits, children were followed up by telephone to identify those with persistent symptoms and children younger than 2 years of age were re‐examined within 48 to 72 hours Follow‐up visits were scheduled routinely after 2 and 6 weeks after initial treatment and monthly thereafter
Notes	We included only the non‐severe AOM episodes in this review (N = 1049 of which 980 were included for primary analysis); children experiencing non‐severe AOM episodes were randomly allocated to either antibiotics or placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomisation not described
Allocation concealment (selection bias)	Unclear risk	Method not described
Other bias	Low risk	ITT analysis ‐ yes, baseline characteristics ‐ balanced
Blinding of participants and personnel (performance bias)	Unclear risk	Identical taste and appearance to amoxicillin and placebo not described
Incomplete outcome data (attrition bias)	Unclear risk	Follow‐up/exclusion of non‐severe episodes for short‐term outcome ‐ treatment: N = 34 (7%) and placebo: N = 35 (7%). Reasons not described