Elewski 2015a.

Methods	Study 1 RCT (parallel) Study design: Double blind Sample size calculation: No Diagnosis mycology: KOH and culture Big toenail specified: Yes Statistical comparisons for outcomes: Yes Duration of follow‐up: At 4 weeks and 12 weeks Time points of measurements: Weeks 2, 6, and every 6 weeks thereafter; at week 48, participants who achieved complete cure or treatment success were followed until week 60 (post‐study follow‐up (PSFU)) Location: United States and Mexico, 27 individual sites (cities/institutions not stated)
Participants	Total n: 594 Age: Mean ± SD: tavaborole 53.6 ± 12.5, vehicle 53.4 ± 12.3 Sex: Tavaborole: men 324/399 (81.2%); women 75/399 (18.8%); Vehicle: men 158/194 (81.4%); women 36/194 (18.6%) Inclusion criteria: People 18 years of age or older with distal subungual toenail onychomycosis involving 20% to 60% of at least 1 TGT were eligible if they had a positive potassium hydroxide (KOH) wet mount and positive culture for dermatophytes, greater than or equal to 3‐mm clear nail measured from the proximal nail fold to the most proximal visible mycotic border, and distal TGT thickness 3 mm or less Exclusion criteria: Patients with proximal subungual or superficial white onychomycosis, severe disease, dermatophytoma, exclusively lateral disease, yellow/brown spikes, co‐infection with nondermatophyte fungi, anatomic abnormalities of the toes or toenails, active tinea pedis (involving the sides or back of the foot, interdigital, or plantar) requiring treatment, history of chronic moccasin‐type tinea pedis (involving the sides or back of the foot), history of other significant chronic fungal disease, psoriasis, lichen planus, known immunodeficiency, significant peripheral vascular disease, known structural heart disease, or uncontrolled diabetes (haemoglobin A1C 8%). Patients who used topical antifungals on the toenails within 4 weeks or systemic antifungals within 24 weeks were also excluded. Recent use of other topical agents on the toe or toenails, systemic corticosteroids, or immunomodulatory agents was not permitted Disease duration: Unknown Comparable at baseline: Yes Causative species: Dermatophytes Number of people lost to follow‐up: Tavaborole: participant request n = 24, lost to follow‐up n = 18, noncompliance n = 2, adverse events n = 1, other n = 7. Vehicle: participant request n = 11, lost to follow‐up n = 5, noncompliance n = 2, adverse events n = 2, other n = 3 Trial duration: December 2010 ‐ November 2012
Interventions	Treatment duration: Once daily for 48 weeks Drug in study arm 1: Tavaborole topical solution 5%, n = 400; PSFU n = 18 Drug in study arm 2: Vehicle, n = 194; PSFU n = 2
Outcomes	Mycological cure (KOH and culture) at week 52 Complete cure (no clinical evidence of onychomycosis and mycological cure) at week 52 and 60 Complete or almost complete clear nail (≤ 10% nail affected) at week 52 Complete or almost complete clear nail (≤ 10% nail affected) plus mycological cure at week 52 and 60 (treatment success) Adverse events: reported
Notes	2 of 9 authors are employees of industry, while the remaining 7 have ties to industry (e.g. advisor, consultant, investigator). Funded by industry. Disclosures accompanied by a quote: "The authors were fully responsible for the content, editorial decisions, and opinions expressed in the current article. No author received an honorarium related to the development of this manuscript."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Email response: "The randomisation (blocks of 6) was stratified by investigational site in a 2:1 ratio to the following treatment groups: tavaborole or vehicle" Comment: Specific randomisation method that is suitable was specified
Allocation concealment (selection bias)	Low risk	Email response: "Treatment assignment was accomplished by a computer generated random sequence implemented through the interactive web randomisation system (IWRS)." Comment: Allocation concealment appropriate
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Email response: "Tavaborole or matching vehicle was supplied in amber glass bottles containing 10 mL of investigational product...neither the Investigator nor the subject knew the subject's treatment assignment." Comment: Blinding was adequate
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Email response: "...neither the Investigator nor the subject knew the subject's treatment assignment. The Sponsor’s staff involved in clinical management, data management, and statistical evaluation was to remain blinded until a database lock memo was issued and identification of the analysis populations was agreed upon and documented." Comment: Blinding was adequate
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: Reasons for participants discontinuing the study were provided for each treatment group. The ITT population was clearly specified
Selective reporting (reporting bias)	Low risk	Comment: Outcomes reported in trial protocol are explicit. The same outcomes are specified and reported verbatim in the publication. One variation of the secondary outcome was added to the publication that is not stated in the trial protocol. NCT01302119
Other bias	Low risk	Comment: Not a multiple intervention trial, but all outcomes reported for interventions