Feng 2015.

Study characteristics
Methods	Study design‐ multicentre, randomised, dose‐ranging placebo‐controlled, parallel‐design in glabellar lines Study date‐ start (25 November 2009), end (27 November 2010) Study setting‐ outpatients from seven centres
Participants	Randomised‐ 448 participants, with mean age of 44.34 years in placebo group; 44.2 years in low‐dose BontA (10 u) group; 42.79 years in high‐dose BontA (20 u). Gender: male 17/122 (13.93%), female 105 /122 (86.07%) in placebo group; male 29/183 (15.85%), female 154/183 (84.15%) in BontA low‐dose group; male 27/183(14.75%), female 156/183 (85.25%) in BontA hig‐ dose group Inclusion criteria Moderate‐or‐severe glabellar lines; and age: 18 to 65 years Exclusion criteria Previous BontA treatment Systemic neuromuscular junction disorder Known allergy to BontA or excipients Disease at an injection site or any conditions interfering with study assessments Cosmetic surgical procedures scheduled during the study period And any significant comorbidity precluding BontA treatment Severity of disease‐ Participants with moderate‐to‐severe glabellar lines Ethnicity‐ no information
Interventions	Duration of study‐ 16 weeks Intervention BontA(HBTX‐A) (10 U) (N = 183), BontA‐ 20 U (N =183) Comparator Placebo‐0.5 mL (N =122)
Outcomes	Primary outcome Clinical glabellar line severity score at maximum contraction on day 30 Secondary outcomes Improvement in graded severity of glabellar lines during relaxation; overall assessment of glabellar line severity reduction; participant satisfaction Adverse events.
Notes	“The authors have indicated no significant interest with commercial supporters.”
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "double‐blind trial and randomly divided into" page S56 Comment: we consider unclear risk of bias because the authors did not explain how they randomised the participants
Allocation concealment (selection bias)	Unclear risk	Quote: "Participants were assigned to low‐dose (10 units, n = 183), high‐dose (20 units, n = 183), or saline" page S57 Commen: we consider unclear risk of bias because the authors did not explain the methods used for maintaining the allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: "Participants who met the inclusion and exclusion criteria were enrolled in a double‐blind, placebo‐controlled" page S57 Comment: we consider unclear risk of bias because the authors did not explain how they blinded the participants
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "Participants who met the inclusion and exclusion criteria were enrolled ina double‐blind, placebo‐controlled" page S57 Comment: we consider unclear risk of bias because the authors did not explain how they blinded the outcome assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Four participants were lost to follow‐up (one in the placebo group, 2 in the low dose, and 1 in the high‐dose group), and excluded from primary end point data. Another 13 participants statistically 'out of the time window' were excluded from analysis, including 5 participants in the placebo group, 5 in the low‐dose group, and 3 in the high‐ dose groups, respectively. One participant in the high‐dose group receiving combined therapy was not included in the per protocol set (PPS). The final PPS consisted of 449 (92.01%) participants, including 111, 167, and 171 in the placebo, low‐dose and high‐dose arms, respectively." page S58 Comment: we consider low risk of bias
Selective reporting (reporting bias)	High risk	The authors did not mention if the investigator assessment was done at rest or at contraction Comment: we consider this high risk of bias, we sent an e‐mail on 21 November 2015. We received no answer
Other bias	Low risk	We considered this study at low risk of other bias