King 1982.

Methods	Parallel design; randomised controlled trial
Participants	48 participants from two centres, Departments of Dermatology from the General Infirmary and from St James’s University Hospital, both at Leeds, United Kingdom Inclusion criteria: failure to respond to conventional therapy, including several courses of antibiotics Exclusion criteria: not stated Age: for all participants, mean age was 25 years Gender: 24 male/24 female Duration of acne: not provided Acne severity: not provided
Interventions	Intervention 1 (n = 13): oral isotretinoin 0.1 mg/kg/day Intervention 2 (n = 21): oral isotretinoin 0.5 mg/kg/day Intervention 3 (n = 14): oral isotretinoin 1.0 mg/kg/day All interventions were administered for 16 weeks
Outcomes	Clinical improvement assessed as percentage change in acne severity on face, back and chest ‐ evaluated by a 0‐10 acne grading scale (Burton 1971; Cunliffe 1981) Changes from baseline in sebum excretion rate measured by a gravimetric method (Strauss 1961) Changes from baseline in production rate of free fatty acids assessed by the method described in Dole 1960 Changes in skin micro‐organisms population assessed by the collection of skin samples from the right cheek using the scrub technique (Williamson 1965) and the determination of the number of bacterial colony‐forming units present per cm2 skin by the method of Miles & Mistra (Miles 1938)
Funding body	Roche Products Limited
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	Unclear risk	Quote: "A double‐blind study of the effects of 13‐cis‐retinoic acid on acne, sebum excretion rate and microbial population". Comment: There was no description of who was blinded and also no description of efforts to ensure blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "A double‐blind study of the effects of 13‐cis‐retinoic acid on acne, sebum excretion rate and microbial population". Comment: There was no description of who was blinded and also no description of efforts to ensure blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: There was no information regarding missing data
Selective reporting (reporting bias)	Low risk	Comment: No protocol available; however, there was an adequate report of outcomes listed in methods section
Other bias	Unclear risk	Comment: The study might be at risk of inappropriate influence of funders, as it was sponsored and promoted by a pharmaceutical company