Malapane 2014

Methods	RCT, double‐blinded, placebo‐controlled pilot study, 6 days' duration
Participants	Setting: a primary school in Gauteng, South Africa Participants: 30; 15 randomised to homeopathy, 15 to placebo Recruitment method: parents or guardians and teachers were requested to refer children reporting a sore throat or tonsillitis to the researcher. Withdrawals and exclusions: none Age range: 6 to 12 years Gender: 73.3% female in placebo group and 53.3% female in treatment group Eligibility criteria: Inclusion criteria: children had to have symptoms of viral tonsillitis (sore throat, pain on swallowing, erythema and/or oedema of the tonsils, and enlarged or tender tonsillar and cervical lymph nodes), recent onset tonsillitis (i.e. ≤ 2 days), and possible presence of exudates on the pharynx and tonsils. Exclusion criteria: positive rapid streptococcal antigen test result; diphtheria; otitis media; lymphadenopathy, except for the tonsillar and cervical lymph nodes; tonsillectomy; a medical history of rheumatic fever or glomerular nephritis; malabsorption syndrome; diseases that compromise breathing stridor (e.g. bronchitis, bronchopneumonia, or very enlarged tonsils); temperature > 39 °C; HIV/AIDS; symptoms of Group AStreptococcus and confirmed diagnosis; using long‐term medication, immune stimulants (including homeopathic or herbal remedies), and/or antibiotic treatment during the previous 14 days; or analgesic, antipyretic, or cold medications (e.g. decongestant, antihistamine, antitussive or throat lozenges) within the previous 8 hours
Interventions	Homeopathic medicinal product versus placebo Each participant was given instructions to dissolve 2 tablets 4 times a day under their tongue (after breakfast, lunch, and supper and before bedtime), with the first dose administered by the researcher. Each child received an information leaflet detailing the dosage and storage instructions. Homeopathic product: the homeopathic complex used in this study was commercially available in the South African market under the trade name Tonzolyt and was marketed for the treatment of acute or chronic tonsillitis and pharyngitis. It includes the following remedies: Atropa belladonna D4, Calcarea phosphoricum D4, Hepar sulphuris D4, Kalium bichromate (potassium dichromate) D4, Kalium muriaticum D4, Mercurius protiodide D10, and Mercurius biniodid D10. The D (or Decimal) potency is created by diluting the crude substance in a 1:10 ratio (i.e. 1 part solute in 10 parts solvent, usually ethanol‐water solution); each dilution is followed by succussions (vigorous shaking against a hard surface). Placebo: the placebo was similar in appearance and taste and was labelled in the same manner as the treatment medication.
Outcomes	Pain score (daily for 6 days) Pain on swallowing Referred ear pain Tonsil size Erythema/inflammation of pharynx Vital signs At each consultation, participants completed the Wong‐Baker FACES Pain Rating Scale and a Symptom Grading Scale (SGS) under the supervision of the researcher, and a relevant physical examination was performed. The SGS was used to grade tonsillar hypertrophy and erythema/inflammation of the pharynx. The researcher also determined the presence of associated ear pain and pain on swallowing using the SGS.
Notes	Author disclosure statement states that no competing financial interests exist. No other mention of funding support
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Assignment to medication or placebo was randomised by an outside party using the simple random sampling method.” (p. 869) Comment: robust method of random sequence generation used.
Allocation concealment (selection bias)	Low risk	Quote: “the participants received one bottle containing 48 tablets of the homeopathic complex medicated onto lactose tablets or un‐medicated lactose tablets. The placebo was similar in appearance and taste and was labelled in the same manner as the treatment medication.” (p. 869) Comment: robust method of allocation concealment used.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: “This was a 6‐day, double‐blind, placebo‐controlled pilot study with daily follow‐up assessments” (p. 869) Comment: although study was stated to be double‐blind, there was no description of how blinding of personnel or participants took place.
Blinding of outcome assessment (detection bias) Patient reported outcomes	Unclear risk	Comment: although study was stated to be double‐blind, there was no description of how blinding of participants took place.
Blinding of outcome assessment (detection bias) Practitioner outcome assessors	Unclear risk	Quote: "The red/inflamed pharynx was measured in ordinal categories: absent (code 0), slightly red (code 2), red (code 4), very red (code 6), severely red (code 8), and extremely red (code 10)." (p. 870) Comment: although study was stated to be double‐blind, there was no description of how blinding of investigators took place. Rating scales for some examination items appear subjective.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No loss to follow‐up, data provided for all 30 enrolled participants
Selective reporting (reporting bias)	Unclear risk	All outcomes described in methods are reported in results, however inadequate raw data provided. Only means of rating scales reported in text, not presented in a table with components of severity that contributed to the final mean score.
Other bias	Unclear risk	Positive outcomes emphasised in the discussion, but lack of clinically significant findings despite statistical significance were played down because of the use of reporting means of rating scales rather than any dichotomous outcomes. Study is of small sample size, allocation concealment poorly described; unequal groups at beginning regarding severity of disease. The duration of pain/symptoms at baseline is not reported, which is vital information when studying a self limiting condition. Despite these issues, the discussion claims “Analysis between groups showed that the homeopathic complex outperformed placebo, with a large effect size. The associated symptom of pain on swallowing also significantly improved over time, while the placebo group did not”. (p. 872) Intervention stated to be well tolerated with no adverse events, however very small sample size with population from a single source and demographic group. Children were self administering medication sublingually with aid of a leaflet – no mechanism described to ensure correct administration technique or adherence.