de Lange de Klerk 1994

Methods	RCT, double‐blinded, parallel study, 1‐year duration
Participants	Setting: paediatric outpatient department of university hospital, Netherlands Participants: 170 participants were randomised: 86/84 to homeopathy/placebo groups Recruitment method: participants were recruited by their general practitioners and by articles in the popular press. Withdrawals and exclusions: 5 children (2 in homeopathy group and 3 in placebo) participated for < 26 weeks and their results were not analysed. Age range: 18 months to 10 years Gender: 47% female Baseline demographics: the median age was 4.2 years in the homeopathy group and 3.6 years in the placebo group. The lifetime prevalence of otitis media with effusion was 64% in the homeopathy group and 52% in the placebo group. Eligibility criteria: Inclusion criteria: children who had at least 3 URTIs in the past year or had 2 previous URTIs as well as otitis media with effusion at the time of entry examination Exclusion criteria: children who had adenoidectomy, tonsillectomy, or a 'constitutional' homoeopathic treatment in the past 6 months; regular medical care for any other chronic condition including chronic non‐specific lung disease; untreated dental caries; congenital malformation of the respiratory tract or the heart; mental handicap; neurological disorder; children with height outside the third centile; a history of rheumatic fever, endocarditis, myocarditis, or nephritis; children for whom no suitable homoeopathic constitutional medicine could be chosen at the entry examination because they did not have at least 3 symptoms relevant for the choice of a matching homoeopathic medicine; and children whose parents were not fluent enough in Dutch to answer the questionnaires
Interventions	Homeopathic medicinal products were chosen individually by a homeopathic practitioner for each participating child. Mainly 6th, 30th, and 200th decimal potencies were used. The homeopathic treatment consisted of constitutional medicines for improving general health in the long run and acute medicines for treating URTIs.
Outcomes	Mean daily symptom score, mean percentage of days symptom‐free, number of antibiotic courses, number of adenoidectomies and tonsillectomies over 1‐year follow‐up
Notes	Insufficient reporting of details of the intervention including medication frequency and which homeopathic medicines were used Funded by a grant from the Dutch Ministry of Welfare, Cultural Affairs and Public Health
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "We assigned children to the study groups using permuted blocks (size 4) stratified for age in (18‐23 months, two to five years, and six to nine years). This achieves balance for age and also for any variables which tend to vary over time or season." (p. 1330) Comment: well‐described methods, low risk of selection bias
Allocation concealment (selection bias)	Unclear risk	Quote: "The identity of the treatment groups was concealed until all the data analysis was complete" (p. 1330) Comment: specific method of allocation concealment was not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The child was given either active medicine or a placebo for the appropriate treatment for the whole study period." (p. 1330) Comment: does not specify whether placebo was indistinguishable from homeopathy, however as long as participants remained unaware of allocation, this detail is unlikely to make a difference
Blinding of outcome assessment (detection bias) Patient reported outcomes	Low risk	Quote: "The parents kept diaries, and their observations were collected once every two weeks through structured telephone interviews." (p. 1330) "We calculated each child's daily symptom score for each day of follow up." (p. 1330) Comment: as parents were blinded, the risk of detection bias for participant‐reported outcomes is likely to be low
Blinding of outcome assessment (detection bias) Practitioner outcome assessors	Low risk	Quote: “The identity of the treatment groups was concealed until all the data analysis was complete.” (p. 1330) "The randomised double blind placebo controlled design was used because we wanted to study the intrinsic effects of the homeopathic medicines, not the effects of the treatment as a whole, including counselling and advice." (p. 1331) Comment: it is likely that treatment groups were blinded throughout assessment given these statements
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "A total of 175 children were eligible for study. Data were analysed for all 170 children who participated for more than 26 weeks, including three children (one in the treatment group, two in the placebo group) who stopped taking trial treatment but continued follow up." (p. 1330) Comment: only 5 of 175 children were excluded from analysis (2 from homeopathy, 3 from placebo) due to less than 26 weeks' participation. Exclusions are accounted for.
Selective reporting (reporting bias)	Low risk	All primary outcomes stated in methods were reported.
Other bias	Low risk	No other bias identified.