Thielitz 2015.

Study characteristics
Methods	Aim of study: to evaluate the efficacy of AZA 15% gel versus no treatment during maintenance therapy of female adult acne and to compare its efficacy and safety versus adapalene 0.1% gel (AD) during a 9‐month period (3‐month treatment and 6‐month maintenance treatment) Design: parallel Unit of allocation: individuals Allocation: randomisation; not reported Blinding: investigator‐blind Duration of trial (from recruitment to last follow‐up): study period was between August 2011 and October 2012 Dropouts at the end of treatment phase: AZA9M (AZA gel twice/day for 9 months): n = 3; AZA3M (AZA gel twice/day for 3 months followed by a 6‐month observational phase): n = 2; AD9M (adapalene 0.1% gel once daily for 9 months): n = 1
Participants	Population description: adult female participants with mild to moderate acne Setting: industry‐sponsored single‐site study in university, Germany Randomised number: 55 Age: AZA9M: 30.58 ± 9.28; AZA3M: 28.14 ± 4.56; AD9M: 28.94 ± 6.71 Sex: all subjects are females of European origin Severity of illness: mild to moderate acne
Interventions	Name of treatment group: AZA9M; n = 17 Description: AZA 15% gel twice daily for 9 months Treatment period: 36 weeks Timing: twice daily Name of treatment group: AZA3M; n = 19 Description: AZA gel for three months followed by a six‐month observational phase Treatment period: 12 weeks Timing: twice daily Name of treatment group: AD9M; n = 19 Description: adapalene 0.1% gel once daily for nine months Treatment period: 36 weeks Timing: once daily
Outcomes	Primary outcomes Participants' global self‐assessment of acne improvement (e.g. measured by a 4‐point scale: excellent, good, fair, and poor). Weeks 6 and 12; seven grades system 1: very much improved, 2: much improved, 3: improved, 4: unchanged, 5: worse, 6: much worse, 7: very much worse Withdrawal for any reason. 6 dropouts during the 12‐week treatment period Secondary outcomes Change in lesion counts (total or inflamed and non‐inflamed separately). Reduction of total, non‐inflamed, and inflamed lesions. Weeks 6 and 12, post‐treatment follow‐up for 6 months Physicians' global evaluation of acne improvement. Authors did not report this outcome Minor adverse events (assessed as total number of participants who experienced at least one minor adverse event). Assessed using a 0‐3 scale (0‐none, 1‐slight, 2‐moderate, 3‐strong). Reported number of participants who experienced minor adverse event Quality of life (QoL). Dermatology Life Quality Index questionnaire (DLQI) Other outcomes that were not analysed in this review Change in acne severity grade (Leeds Revised Acne Grading Scale)
Notes	Funding: Intendis GmbH, Max‐Dohrn‐Str. 10, 10589 Berlin, Germany. This was an investigator‐initiated trial. The funder was not involved in the development of the study protocol, the data collection or analysis and the preparation of the manuscript.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The three arms were randomised in the ratio 1 : 1: 1, using the minimization method of Pocock and Simon and a stratification for age (18–29 years; 30–45 years) and severity classification at study entry..." Comment: minimisation method is reliable for random sequence generation
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "The study materials were dispensed by a designated person other than the investigator and the subjects were instructed not to discuss the study materials, treatment schedule and potential side‐effects with the investigator". Comment: the subjects are not blinded and the investigators seemed blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "The study materials were dispensed by a designated person other than the investigator and the subjects were instructed not to discuss the study materials, treatment schedule and potential side‐effects with the investigator". Comment: unclear whether outcome assessor was blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	The author performed both ITT and per‐protocol analysis, reasons for attrition reported
Selective reporting (reporting bias)	Low risk	Results reported for all prespecified outcomes in the study protocol
Other bias	Low risk	No other potential bias identified