Drake 1997.

Methods	Design: parallel group RCT
Participants	Number of participants randomised: 358 Sex: 77% male Mean age: 45 years Number included in analysis: 238 Number completing treatment: not stated Inclusion criteria: mycological confirmation of onychomycosis and evidence of ability of nail to grow Type/location/characteristics of infection: distal subungual onychomycosis of at least 1 great toenail (if both great toenails affected, more severe was selected for observation and testing) Duration of infection: not stated Exclusion criteria: psoriasis, proximal subungual onychomycosis, superficial white onychomycosis Washout period: 3 months for oral antifungals, 1 month for topical antifungals Setting: multicentre, USA and Canada Comorbidities: not stated
Interventions	Placebo (24 weeks) Oral terbinafine 250 mg once daily (12 weeks) then placebo (12 weeks) Oral terbinafine 250 mg once daily (24 weeks)
Outcomes	Duration of follow‐up: 24 weeks follow‐up without treatment. Those with negative mycology and > 5 mm unaffected nail growth were followed up for an additional 48 weeks Outcomes measured: negative mycology (negative culture and KOH), length of unaffected nail,% nail involvement, participant‐ranked response to therapy (excellent, very good, slight improvement, fair, poor/no effect), recurrence rate Safety and tolerability assessed by ‐ physical exam, vital signs, lab evaluation (haematology, LFTs, bilirubin), reports of adverse events
Source of funding	Supported by Novartis pharmaceuticals cooperation
Conflict of interest	Clear disclosure of pharmaceutical industry funding (Novartis), several authors work for Novartis
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "[p]atients were randomised" Comment: method of random sequence generation not stated. Baseline characteristics similar for different groups
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment not stated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "[t]he 96‐week study included a double‐blind treatment phase of 24 weeks in which patients were randomly assigned to one of three parallel groups: oral terbinafine for 12 weeks then placebo for 12 weeks, oral terbinafine for 24 weeks, or placebo for 24 weeks." "This phase was followed by 24 weeks of blinded follow‐up without treatment (weeks 24 to 48)" Comment: study states participants were blinded, and all treatment groups were given therapy for the same duration; however it is unclear if placebo and terbinafine were indistinguishable
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "[m]ycologic and clinical assessments were performed on the 'target' nail" Comment: study states evaluators were blinded, but no detail on method of blinding
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "[a] total of 358 patients … were enrolled." "Patients were randomly assigned to one of three parallel groups in a 2:2:1 ratio: oral terbinafine for 12 weeks (N = 142), oral terbinafine for 24 weeks (N = 145), or placebo (N = 71)." "At week 48, 70% of patients treated with terbinafine for 12 weeks and 87% of patients treated for 24 weeks exhibited both negative microscopy and negative culture versus 9% for placebo‐treated patients." No patient numbers provided for these percentages Comment: number of participants reported in outcome data is not always clear 358 participants were randomised (287 into terbinafine groups and 71 into placebo group). The number included in short‐term follow‐up data is unclear as only percentages are reported. For long‐term follow‐up, where actual patient numbers are reported, 238 participants were included in long‐term follow‐up analysis; those with new unaffected nail by week 48 were designated by protocol to be followed up for an additional 48 weeks.
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