Halsted 1968.

Methods	Randomised ‐ yes, pre‐determined code, which was unknown to physician; method of random sequence generation unclear Concealment of allocation ‐ adequate Double‐blind ‐ yes Intention‐to‐treat (ITT) ‐ unclear Loss to follow‐up ‐ described, unclear from which treatment group patients were excluded Design ‐ parallel
Participants	N ‐ 106 children (N = 89 children included in analysis; N = 12 children were excluded because they did not adhere to the double‐blind protocol; N = 5 children lost to follow‐up or excluded because of persistent fever, development of complication requiring antibiotic treatment or if group A streptococci was cultured from the middle ear) Age ‐ between 2 months and 5.5 years Setting ‐ secondary care: paediatric department of Cleveland (USA) Inclusion criteria ‐ AOM based on otoscopic findings; most of the cases had bulging membrane with loss of normal light reflex and landmarks, in a few the eardrum was only diffusely red Exclusion criteria ‐ antibiotic treatment < 10 days prior to randomisation, associated bacterial infection requiring antibiotic treatment, rupture of tympanic membrane, contraindication for study drugs Baseline characteristics ‐ not described
Interventions	Tx 1 ‐ ampicillin 100 mg/kg/day 4 daily for 10 days; N = ? (N = 30 included in analysis) Tx 2 ‐ pheneticillin 30 mg/kg/day 4 daily and sulfisoxazole 150 mg/kg/day 4 daily for 10 days; N = ? (N = 32 included in analysis) C ‐ placebo for 10 days; N = ? (N = 27 included in analysis) Use of additional medication ‐ phenylephrine nose drops and aspirin for children over 6 months was prescribed as necessary; no other medications were employed
Outcomes	Primary outcome ‐ early improvement defined as defervescence and decrease of symptoms at 24 to 72 hours Secondary outcomes ‐ (a) late improvement defined as resolution of symptoms and normal tympanic membrane at 14 to 18 days, (b) bacteriological cultures
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Pre‐determined code, which was unknown to physician; method of random sequence generation unclear
Allocation concealment (selection bias)	Unclear risk	Method not described
Other bias	Unclear risk	ITT analysis ‐ unclear, baseline characteristics ‐ not described
Blinding of participants and personnel (performance bias)	Unclear risk	Identical taste and appearance to antibiotics and placebo not described
Incomplete outcome data (attrition bias)	Unclear risk	Reasons described, unclear from which treatment group patients were excluded