Kawashima 2015.

Methods	Study design: parallel design Duration of follow‐up: 12 weeks
Participants	Total number of participants randomised: N = 800 Inclusion criteria Male and female participants aged 12 to 45 years 17 to 60 inflammatory lesions, 20 to 150 non‐inflammatory lesions Investigator’s Static Global Assessment (ISGA) score ≥ 2 (mild) Exclusion criteria Nodulo‐cystic lesions History or presence of regional enteritis, inflammatory bowel disease, or similar symptoms Use of prohibited medications or procedures improving or exacerbating acne within specified washout periods Hypersensitivity or previous allergic reaction to any component of study drugs Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator’s Static Global Assessment (ISGA) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 65/139; B = 109/187; C = 97/202 Age (years): A = 20.4 (6.1); B = 20.7 (6.3); C = 21.1 (6.5) Duration of acne (years): unclear
Interventions	Interventions in Group A* Topical treatment: clindamycin/BPO Regimen: leave‐on Concentration: clindamycin: 1%; BPO: 3% Vehicle: gel Dose: once daily Duration: 12 weeks Number of participants assigned: 204 Interventions in Group B* Topical treatment: clindamycin/BPO Regimen: leave‐on Concentration: clindamycin: 1%; BPO: 3% Vehicle: gel Dose: twice daily Duration: 12 weeks Number of participants assigned: 297 Interventions in Group C Topical treatment: clindamycin Regimen: leave‐on Concentration: 3% Vehicle: gel Dose: twice daily Duration: 12 weeks Number of participants assigned: 299 Co‐interventions: none
Outcomes	Primary outcomes of review interest Withdrawal due to adverse effects Secondary outcomes of review interest Investigator‐assessed change in lesion counts** Percentage of participants rated 'clear' or 'almost clear' on the Investigator Global Assessment (IGA) scale of acne severity Reduction in C acnes strains (total and clindamycin‐resistant) Percentage of participants experiencing any adverse event Other outcomes reported in the study Proportion of participants who achieved a minimum 2‐grade improvement in ISGA score Proportion of participants with ≥ 50% reduction in TL counts Investigator‐assessed local skin tolerability for erythema, dryness, and peeling on a scale ranging from 0 (none) to 4 (severe) Participant‐assessed local skin tolerability for itching and burning/stinging on a scale ranging from 0 (none) to 4 (severe) Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 **This outcome was assessed as the primary outcome in the trial
Study details	Study period: unclear Country: Japan Setting: unclear Number of study centres: 26 Washout period: 2 weeks for topical anti‐acne medications (e.g. BPO, azelaic acid, resorcinol, salicylates, antibiotics); 4 weeks for topical corticosteroids, facial procedure; 12 weeks for oestrogens, androgens, or anti‐androgenic agents; 6 months for systemic or topical retinoids Registered number: NCT01445301 ITT analysis: yes
Publication details	Language of publication: English Funding: commercial Conflicts of interest: "M.K. served as a coordinating investigator and a third‐party reviewer of facial photographs, for which he received compensation, and has served as a consultant for other pharmaceutical companies. M.Y., H.H. and M.O. are employees of GSK, Tokyo, Japan. A.B.A.S. is a dermatologist and an employee of Stiefel, a GSK company" Publication status: full article
Stated aim for study	Quote from publication: "this multicentre study was conducted to evaluate the efficacy and safety of CLNP/BPO 3.0% gel applied once daily or twice daily relative to CLNP twice daily when applied topically for 12 weeks in Japanese patients with acne"
Notes	*Data from group A and group B were combined for the meta‐analysis in this review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "using a computer randomization system, eligible patients were randomized (2:3:3) to receive CLNP/BPO 3 0% once daily, CLNP/BPO 3 0% twice daily, or CLNP twice daily" Comment: the method used to generate the random sequence was specified
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information on the method of allocation concealment used was provided
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: the trial was single‐blind and investigators were blinded, indicating that participants were not blinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "to keep the single blinding, investigators were not permitted to ask about or collect any information related to the dose regimen, colour of the gel, external appearance or weight of the tubes, or to access patient compliance records" Comment: although blinding was conducted, complete blinding was difficult as it was reported that treatment‐related adverse events were more common in the 2 BPO/clindamycin groups
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: the proportion of withdrawals and corresponding reasons were not similar between the 3 groups
Selective reporting (reporting bias)	Low risk	Comment: all outcomes planned on the trial registry have been reported
Other bias	Low risk	Comment: according to Table 1, demographics and baseline disease characteristics were similar across both groups. Washout periods were long enough