Sinha 2012

Methods	Randomised, placebo‐controlled, parallel‐group pilot study, 11 months' duration
Participants	Setting: the General Paediatric Clinic of the Regional Research Institute of Homeopathy in Jaipur, India Participants: 80; 40 randomised to homeopathy, 40 to conventional treatment Recruitment method: clinic patients Withdrawals and exclusions: 2 in homeopathy group due to lack of follow‐up. 1 excluded from conventional treatment group due to convulsions. Age range: 2 to 6 years Gender: 50% female Eligibility criteria: Inclusion criteria: earache of no more than 36 hours' duration; tympanic membrane bulging with loss of landmarks Exclusion criteria: children having any discharge or history of discharge from ear; history of convulsions; subperiosteal abscess of mastoid; grossly deviated nasal septum; suspected enlarged adenoids (persistent nasal discharge, snoring, history of tonsillar hypertrophy); OME; on antibiotics in the past 7 days or on corticosteroid therapy; suffering from any systemic disease
Interventions	Homeopathy group: children in homeopathy group were prescribed appropriate homeopathic medicinal products in 50 millesimal (LM) potencies. Medicine was repeated 2 to 6 hourly depending upon the severity of child’s signs/symptoms. “Repertorisation was done on the basis of totality of symptoms by using CARA software. After repertorisation, medicine was selected on the basis of Homeopathic Materia Medica.” The potency and the identity of the medicine was changed according to the outcome of the first prescription. A maximum of 2 changes in prescription were permitted. Medicines prescribed were: Arsenicum album (1), Calcarea carbonica (1), Chamomilla (4), Cina (1) Hepar sulphuratum (1) Lycophodium clavatum (3) Mercurius solubilis (7) Pulsatilla nigricans (14) Silicea (6) sulphur (2). Conventional treatment group: observation for 3 days (and treatment with antipyretics, anti‐inflammatories). Then prescription of antibiotics if less than 50% improvement on AOM‐SOS and tympanic membrane scales. Antibiotics prescribed were azithromycin (17 children) and amoxicillin (22 children).
Outcomes	Change of symptoms (0 to 21 days) Time to cure using AOM‐SOS scale plus tympanic membrane scale Signs on tympanic membrane exam
Notes	No mention of any funding sources, no conflict of interest statement available
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Randomization was done by a computer generated random number list to receive either of the interventions” (p.7). “The participant’s enrolment numbers were used for the purpose of randomisation.” (p. 7) Comment: use of random number generator suggests robust random sequence generation.
Allocation concealment (selection bias)	Unclear risk	Quote: “The parents/guardian and the research personnel remained unaware of the participant’s group assigned throughout the study.” Comment: specific allocation concealment such as coded bottles not described.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: “The parents/guardian and the research personnel remained unaware of the participant’s group assigned throughout the study.” (p. 7) Comment: does not give details of blinding, e.g. double‐dummy technique or method of making treatments indistinguishable to participants. In conventional treatment group, children were given symptomatic treatment with analgesic, anti‐inflammatory, and antipyretics, which are likely to be identifiable as separate from homeopathy (there would need to be a separate protocol for giving these medications as they are not safe to repeat 2 to 6 hourly depending upon the severity of child’s signs/symptoms). Therefore high risk of homeopathy and conventional treatment groups being identifiable to participants.
Blinding of outcome assessment (detection bias) Patient reported outcomes	High risk	Quote: "To assess the severity of disease, response of each patient was noted by the investigator and ENT Specialist as per the information gathered from parents/guardians on AOM‐SOS scale and with the help of Tympanic Membrane Examination scale on third, seventh, tenth and 21st day respectively." (p. 8) Comment: the 2 treatment groups' interventions were quite different, e.g. conventional analgesics and antipyretics versus homeopathy regimen. In the absence of clear documentation as to how these regimens were made indistinguishable, blinding of outcome assessment for parent‐reported outcomes cannot be relied upon.
Blinding of outcome assessment (detection bias) Practitioner outcome assessors	Unclear risk	Quote: "In both the groups, patients were followed up in person on third, seventh, tenth and 21st day assessed with the AOM‐SOS scale and Tympanic Membrane Examination scale." "In homeopathy group, all follow‐ups were done as per the guidelines laid down for the second prescription in the protocol, i.e. increasing the potency and change of medicine depending on the outcome of the first prescription." (p. 8) Comment: does not give any detail of blinding or if ear, nose, and throat specialists performing tympanic membrane exams were blinded. The above quote suggests that practitioner may be aware of group, as for homeopathy participants they were adjusting the prescription.
Incomplete outcome data (attrition bias) All outcomes	Low risk	2 children in homeopathy group did not attend last 2 follow‐ups, but were still included in analysis (last observation carried forward). One child in conventional treatment group was excluded from study due to hospitalisation with convulsions. Comment: minimal dropouts, which are accounted for
Selective reporting (reporting bias)	Unclear risk	No data reported on results of AOM‐SOS scale, the measure of symptom severity for this trial, despite the importance of this result in the study design for deciding on addition of antibiotic medication.
Other bias	High risk	Quote: "No patient in the Homeopathy group required antibiotics" (p. 11) Comment: inconsistency in the methods ‐ homeopathy group and conventional treatment group were treated differently. Although the methods state "In both groups, if less than 50% improvement was observed in first 3 days of treatment, antibiotics were given" (p. 8), this was apparently not the case. It appears that antibiotic commencement at the 3‐day mark occurred only for the conventional group, not the homeopathy group. In the homeopathy group, only 4 children were cured at day 3, and the mean symptom score for homeopathy participants was reduced by less than 50% (from 14.28 to 8.18), making it impossible that all homeopathy group participants had a 50% improvement in the first 3 days of treatment. However, no homeopathy participants were commenced on antibiotics. The study makes much of the fact that "In Homeopathy group antibiotics were not required for any case." (p. 11). It seems that the total symptom score was a sum of the AOM‐SOS scale and the Tympanic Membrane Examination scale, with a maximum score of 22. We suspect that the criteria for commencing antibiotics was a score above 11, which is not actually the same as less than 50% reduction in symptoms score for each child. The placebo group had a higher mean symptom score at the commencement of the study, so a larger percentage would be above a fixed numerical score, even with an identical amount of symptomatic improvement. This is a major bias within the study design.