Gupta 2005.

Methods	Design: parallel group RCT
Participants	Number of participants randomised: 151 Sex: not stated (both sexes included) Mean age: not stated Number included in analysis: 135 Number completing treatment: 135 Inclusion criteria: onychomycosis confirmed by direct microscopy and/or fungal culture Type/location/characteristics of infection: distal subungual onychomycosis of 1 great toenail (min area 25%), and at least 2 mm proximal nail clear Duration of infection: not stated Exclusion criteria: conditions known to produce abnormal‐appearing nails (psoriasis), proximal subungual onychomycosis, white superficial onychomycosis, allergy to azole drugs, use of drugs that prolong QT interval, abnormal LFTs Washout period: 3 months for oral antifungals, 2 weeks for topical antifungals Setting: 10 dermatology practices in USA, Canada, France Comorbidities: not stated
Interventions	Placebo (12 weeks) Ravuconazole 200 mg/day (12 weeks) Ravuconazole 100 mg/week (12 weeks) Ravuconazole 400 mg/week (12 weeks)
Outcomes	Duration of follow‐up: 36 weeks after treatment Outcomes measured: effective cure (mycological and clinical cure or > 30% improvement), percentage of nail plate infected, length of unaffected nail, mycological examination of cultures, concentrations of ravuconazole in plasma and in toenails Safety and tolerability assessed by: adverse event reports, haematology, serum chemistry, urinalysis
Source of funding	No information available
Conflict of interest	No conflict of interest identified
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "[u]pon subject enrolment, subject number and treatment assignment were obtained from a central call‐in randomization system". "Age, sex and race distribution was similar between the four treatment groups." Comment: likely robust randomisation using this method. Baseline characteristics similar between treatment groups
Allocation concealment (selection bias)	Low risk	Quote: "[u]pon subject enrolment, subject number and treatment assignment were obtained from a central call‐in randomization system". Comment: allocation concealment likely achieved using the method above, as patients very unlikely unable to preempt treatment allocation prior to study enrolment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "[m]edication was administered in a double‐dummy fashion. Placebo tablets were identical to the treatment drug tablets. Neither subject nor evaluating physician was aware of which treatment group the subject had been assigned to." Comment: blinding of participants and personnel likely adequate using this double‐dummy method
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "[n]either subject nor evaluating physician was unaware of which treatment group the subject had been assigned to". Comment: outcome assessment likely blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "[o]ne hundred and fifty‐one subjects were randomised by 10 investigators in three countries … Of these 151 subjects, 148 received at least one dose of the study medication, and 135 were evaluable at the end of the study." "Of the 16 subjects who were randomised to treatment but were not evaluable at the test of cure visit, three were not treated because of withdrawal of consent or inability to comply with protocol requirements. Of the 13 treated subjects who were randomised to treatment but not evaluable at the test of cure visit, three had no test of cure evaluation performed, and 10 subjects did not complete the study". Comment: low number of dropouts, with reasons for exclusion explained Sufficient data provided to complete ITT analysis
Selective reporting (reporting bias)	Low risk	All results presented as set out in the Methods. All prespecified outcomes appear to be reported.
Other bias	Low risk	No clear other bias seen