Arenas 1991.

Methods	Design: open‐label RCT
Participants	Number of participants randomised: unclear, initially stated 90, but participants that did not show a response or did not attend appointments where eliminated from the studies and replaced Number included in analysis: 83 Sex: not stated but M/F ratio 3:1 Mean age: 40.5 years (range 20‐60) Number completing treatment: unclear, see above Inclusion criteria: onychomycosis in the first toe, diagnosed by clinical examination or laboratory findings Type/location/characteristics of infection: first toe only Duration of infection: not stated Exclusion criteria: pregnancy or breastfeeding, treatment in the last month prior to the study Washout period: 1 month Setting: hospital dermatology department in Mexico Comorbidities: not stated
Interventions	Itraconazole 100 mg (oral) + isoconazole 1% (topical) Itraconazole 100 mg (oral) + urea 40% (topical) Itraconazole 100 mg (oral) + placebo(topical) Griseofulvin 500 mg (oral) + isoconazole 1% (topical) Griseofulvin 500 mg (oral) + urea 40% (topical) Griseofulvin 500 mg (oral) + placebo(topical)
Outcomes	Monthly millimetric measurements of the nail
Source of funding	No information available
Conflict of interest	No conflict of interest identified
Notes	Not included in the meta‐analysis due to methodological issues, namely the exclusion and replacement of participants that did not respond to treatment; total number of participants unclear, we have written to the author, but he has not been able to provide the needed data yet
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "[p]atients were randomly selected to enter the study and were divided into two groups of 45 patients each." "Patients were assigned a number according to the order in which they came to the clinic and were randomly included in any of the following groups." Comment: no evidence provided of any method of random sequence generation
Allocation concealment (selection bias)	High risk	Quote: "[p]atients were assigned a number according to the order in which they came to the clinic and were randomly included in any of the following groups." Comment: given that order of presentation to clinic was used to assign a number and it was an open‐label study, there is no suggestion of any allocation concealment being done.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "[a] comparative, open, prospective, longitudinal study" Comment: open‐label study, no blinding
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "[a] comparative, open, prospective, longitudinal study with a blind evaluator was undertaken" Comment: no method of blinding the outcome assessor was detailed.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quotes: "[p]atients were eliminated from the study if they did not keep up their appointments, became pregnant during the study, did not show improvement of clinical symptoms or mycosis after 3 months of treatment, or reported side effects." "Side effects were recorded and most of the patients who were eliminated from the study were substituted with other patients." "In subgroup I/U (14 patients) one patient dropped out and in subgroup I/P (12 patients) one patient dropped out and two patients were eliminated; and in subgroup G/Is (13 patients) two patients experienced side effects and in subgroup G/U (14 patients) one patient experienced side effects. In subgroups I/Is and G/P all patients finished treatment." Comment: participants that did not respond to treatment were replaced. risk of incomplete outcome data given the replacement of participants who were eliminated or dropped out. 7 of an original 90 patients were not included in results.
Selective reporting (reporting bias)	Low risk	Quote: "[m]ethods: monthly millimetrical measurements of the nail were taken according to the Zaias method." Comment: results described 'cure' rates. No mention of millimetrical measurements in Results. All outcome measures presented as set out in the Methods. All prespecified outcomes appear to be reported.
Other bias	Low risk	No other sources of bias seen