Wu 2010.

Study characteristics
Methods	Study design‐ multicentre, randomised double‐blind, placebo‐controlled, parallel‐design in glabellar lines Study date‐ no information Study setting‐ outpatient from four centres
Participants	Randomised 227 participants, with median age of 41.7 years in BontA group, and 44.1years in placebo group. Gender: 142/170 (83.5%) female, 28/170 (16.5%) male in BontA group; 53/57 (93%) female, 4/57 (7%) male in placebo group Inclusion criteria Participants were required to be aged 18 to 65 with glabellar lines of at least moderate severity at maximum frown (graded on a 4‐point facial wrinkle scale: 0 = none, 1 = mild, 2 = moderate to 3 = severe) Participants were also required to be able to complete the entire course of the study and to comply with study instructions Exclusion criteria Any treatment with botulinum toxin before the study Systemic nerve conduction junction disorder (e.g. myasthenia gravis or Eaton‐Lambert syndrome) Known allergy or sensitivity to the study medication or its components Infection or other skin disease at injection sites Any condition that might confound study results (e.g. marked facial asymmetry or eyelid ptosis) Any other planned facial cosmetic or aesthetic medical treatment (e.g. face lift surgery, resurfacing, filler treatment) during the study period Severe heart, kidney, or lung disease Pregnancy, lactation, or participants planning a pregnancy Severity of disease‐ moderate severity at maximum frown (graded on a 4‐point facial wrinkle scale: 0 = none, 1 = mild, 2 = moderate to 3 = severe) BontA (FWS at maximum frown) 86/170 (50.6%) moderate, 84/170 (49.4%) severe Placebo (FWS at maximum frown) 27/57 (47.4%) moderate, 30/57 (52.6%) severe Ethnicity‐ 100% Chinese
Interventions	Duration‐ 16 weeks Intervention OnabotulinumtoxinA (20U), 4 U per site, 2 in each corrugator muscle and 1 in the procerus muscle (N = 170) Comparator Placebo 0.5 mL, 2 in each corrugator muscle and 1 in the procerus muscle (N = 57)
Outcomes	Primary outcome Investigator's rating of wrinkle severity at maximum frown and rest Secondary outcome Participant's global assessment Self‐perception of age Adverse events
Notes	"GlaxoSmithKline provided funding and study material."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "A total of 227 patients were randomised to receive a single treatment of 20 U of BontA or identical placebo in a ratio of 3:1" page 102‐3 Comment: we considered unclear risk of bias because the authors did not explain how they allocated the participants
Allocation concealment (selection bias)	Unclear risk	Quote: "A total of 227 patients were randomised to receive a single treatment of 20U of BontA or identical placebo in a ratio of 3:1" page 102‐3 Comment: we considered unclear risk of bias because the authors did not explain the methods used for allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Vials of BoNTA and placebo had identical investigational labels, which prevented identification of the contents." page 103 Comment: we considered low risk of bias
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	no information Comment: we considered unclear risk of bias because the authors did not explain how they maintained the blindness of the assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Of 258 subjects screened, 227 were randomised, with 170 in the BoNTA group and 57 in the placebo group; 222 completed the study. Reasons for discontinuation included SAEs (one breast cancer and one gastric cancer) that the investigator considered to be unrelated to the treatment, withdrawal from the study (N = 2), and loss to follow‐up (n = 1)" page 104 Comment: we considered this low risk of bias
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported Comment: we considered this low risk of bias
Other bias	Low risk	We considered this study at low risk of other bias