Goldstein 1982.

Methods	Parallel design, randomised controlled trial
Participants	56 participants from multiple centres, three Departments of Dermatology, in United States of America Inclusion criteria: male participants with severe, treatment‐resistant nodulocystic acne; good general health; and to have at least ten inflammatory acne nodules or cysts, 4 mm or more in diameter, on the face, back, or chest Exclusion criteria: not stated Age: for all participants, ranged from 14 to 54 years (mean: 23.4 years) Gender: 100% male Duration of acne: average period of 8 years (range: 2 to 26 years) Acne severity: severe
Interventions	Intervention 1: (n = 28) oral isotretinoin 1.0 mg/kg/day Intervention 2: (n = 28) oral etretinate 1.0 mg/kg/day Both drugs were administered in two divided doses daily, for 8 weeks
Outcomes	Percentage change in lesion counts of the face, chest, and back, limited to inflammatory nodules, 4 mm or greater in diameter Changes from baseline in sebum excretion production (Strauss 1961) Frequency of any side effects evaluated subjectively* The three outcomes above were assessed at each visit and performed at baseline, 2, 4, and 8 weeks of therapy and at 4 and 8 weeks post‐therapy Laboratory alterations assessed by: urinalysis, complete blood count, and blood chemistry determinations repeated after 1, 2, and 8 weeks of therapy; semen analyses, including determination of sperm count, motility, and morphology, performed at baseline and the end of therapy and 8 weeks later* Frequency of ophthalmologic alterations assessed by examination, including dilated slit‐lamp and determination of ocular tension, done on each participant at baseline and after completion of drug therapy* * Indicates outcomes which matched those prespecified for this review
Funding body	None stated
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: The trial did not provide any information about random sequence generation
Allocation concealment (selection bias)	Unclear risk	Comment: There was no statement regarding methods of allocation concealment in the study
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "A multicenter double‐blind study..." "The capsules were coded and dispensed in such a fashion that neither the patients nor the examining physician knew which retinoid was being administered". Comment: There was a description of who was masked during the conduct of the trial, despite no description of any evaluation of the success of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "...neither the patients nor the examining physician knew which retinoid was being administered". Comment: This statement did not clarify whether all outcome assessors were blinded. It was not clear in the report if all the outcome assessments and the clinical evaluation of participants were done by the same people from the study staff
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "All fifty‐six patients completed the 8‐week course of drug therapy, and fifty‐one of these completed the 8‐week follow‐up period." Comment: The report did not provide detailed numbers and reasons for missing data in each intervention group
Selective reporting (reporting bias)	Low risk	Comment: No protocol available; however, there was an adequate report of outcomes listed in methods section
Other bias	Low risk	Comment: There were no other apparent sources of bias