Jacobs 2001

Methods	RCT, double‐blinded, controlled pilot study, 6 weeks duration
Participants	Setting: private group paediatric practice in Seattle, WA, USA Participants: 75; 36 randomised to homeopathy, 39 to placebo Recruitment method: clinic patients Withdrawals and exclusions: 3 children (2 from homeopathy, 1 from placebo) lost to follow‐up Age range: 18 months to 6 years Gender: 40% female Eligibility criteria: Inclusion criteria: diagnosis of otitis media (when there was middle ear effusion, along with 1 or both of: ear pain characterised as moderate or severe, fever of greater than 38 °C orally). Middle ear effusion determined by pneumatic otoscopy. Exclusion criteria: children with a history of ear pain for greater than 36 hours or those who had received antibiotics within the past week or homeopathic medications within the previous 72 hours; children who had previous tonsillectomy, adenoidectomy, or tympanostomy tubes as well as those with a perforated tympanic membrane and/or a discharge from the ear; children on concurrent medication for another acute or chronic illness; children with a cleft palate or Down syndrome
Interventions	Homeopathic medicinal product versus placebo Homeopathic product: children were given individualised homeopathic medicine. 8 different medications were prescribed in the study, but the 4 most common were prescribed in 88% of cases: Pulsatilla nigricans (62.7%) Chamomilla (10.7%) Sulphur (9.3%) Calcarea carbonica (5.3%) Medications were prepared on No. 38 lactose pellets impregnated and tumbled dry with an identical amount of either a homeopathic medication in the 30C potency, prepared in accordance with Homeopathic Pharmacopoeia of the USA, or placebo (water/alcohol solution lacking active substance).
Outcomes	Number of treatment failures at 5 days, 2 weeks, and 6 weeks; diary symptom score during first 3 days; middle ear effusion at 2 and 6 weeks' post‐treatment Outcomes provided by correspondence with author: cure rate (no symptoms or significant reduction in symptoms), mean daily symptom scores Adverse events
Notes	Funded by a grant from the Standard Homeopathic Company
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “For each of the 16 individual homeopathic medicines... coded bottles that had been randomised to contain either active medication or placebo using a random number generator and pattern blocks of 4 and 6.” (p. 179) Comment: use of random number generator suggests robust random sequence generation.
Allocation concealment (selection bias)	Low risk	Quote: “Study medications were randomised into code bottles by a pharmacist at the Standard Homeopathic Company in Los Angeles, who held the code until the study was completed.” (p. 180) Comment: robust allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: “One half of the children were given active homeopathic medicine, and the other half received placebo.” (p. 179); “There were no detectable differences in taste, odour or colour between the treatment medication and placebo” (p. 180) Comment: adequate blinding of children and parents. Homeopathic practitioners blinded. Low risk of broken blinding, as homeopathy and placebo were identical.
Blinding of outcome assessment (detection bias) Patient reported outcomes	Low risk	Parents assessed children’s symptoms and were adequately blinded.
Blinding of outcome assessment (detection bias) Practitioner outcome assessors	Low risk	Quote: “Follow‐up visits were made by an otolaryngology resident (LD), who was blinded as to treatment allocation” (p. 179) Comments: outcome assessors of follow‐up visits were also blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Participant‐reported outcomes:all participants in homeopathy group returned symptom diaries. 6/39 participants in placebo group did not return symptoms diary. No data exclusions made from returned forms. Practitioner‐assessed outcomes: 3 children (2 from homeopathy, 1 from placebo group) lost to follow‐up. No data exclusions made from returned participants.
Selective reporting (reporting bias)	Low risk	All primary outcomes mentioned in methods reported.
Other bias	Low risk	High‐quality reporting of methods and no risk of other bias identified.