Ascher 2004.

Study characteristics
Methods	Study design‐ multicentre, randomised, double‐blind, parallel‐design in glabellar lines Study date‐ start date March and June 2002” no information about end date Study centre‐ outpatients from three centres
Participants	Randomised 119 participants with mean age of 48. 6 ±7.9 years in BontA 25 U group; 50.9 ± 7.5 years in BontA 50 U group; 48.8 ± 7.7 years in BontA75u group; 48.3 ± 6.4 years in placebo group; 49. 3 ±7.5 years total population. Gender: 114/119 (95.8%) female and 5/119 (4.2%) male in total population, 33/34 (97.1%) female and 1/34 (2.9%) male in BontA 25 U group; 32/34 (94.1%) female and 2/34 (5.9%) male in BontA 50 U group; 32/34 (94.1%) female and 2/34 (5.9%) male in BontA75 U group; 17/17 (100% female) and 0/17 (0%) male in placebo group Inclusion criteria Males and females aged 18‐70 years with moderate to severe (grade 2 and 3) glabellar lines during maximum frown and at rest Exclusion criteria Previous face procedure (dermabrasion, fillers) in the face or any prior botulinum toxin treatment in the last 12 months Ptosis or facial nerve palsy that can confound efficacy and safety. Previous insertion of non‐absorbable material or surgical removal of the corrugator, procerus or supercilii, or a combination of these Participants taking medication, with facial conditions affecting neuromuscular function Women with pregnancy test positive Severity of disease‐ moderate to severe glabellar lines at rest Ethnicity‐ no information
Interventions	Duration of study‐ 24 weeks Intervention  AbobotulinumtoxinA (25 U) (N = 34), AbobotulinumtoxinA 50 U(N = 34) AbobotulinumtoxinA (75 U) in glabella, 0.05 mL/site, 5 points (N = 34) Comparator Placebo in glabella (0.05 mL per injection, 5 injections) (N = 17)
Outcomes	Primary outcome Percentage of responders defined as patients with grade 0 or 1 glabellar line (standardised severity scale of 0 = none to 3 = severe) at rest 1 month after treatment, glabellar lines at rest and maximum frown by the investigator (4‐point) Secondaries outcomes Criteria from day 14 to month 6 allowed us to assess the time course and duration of action of the treatment. Adverse events
Notes	“Supported by Beaufour Ipsen Pharma SAS. Disclosure: Dr Zakine is an employee of Beaufour Ipsen Pharma”
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "This multicenter, randomised, double‐blind study compared..." page 224 "Patients were randomly assigned to receive BTX‐A, according to a computer‐generated randomisation schedule" page 225 Comment: we considered low risk of bias
Allocation concealment (selection bias)	Unclear risk	No information available to allow a judgement Comment: we consider this unclear risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "To maintain the study blind, treatments were reconstituted and syringes for injection prepared by a third party not involved with the patient treatment or assessment" page 225 Comment: we considered this low risk of bias
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "double‐blind... study" To maintain the study blind, treatments were reconstituted and syringes for injection prepared by a third party not involved with the patient treatment or assessment" page 224/225 Comment: we considered this low risk of bias
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote:"two patients withdrew before the first month" page 227 Comment: we considered a unclear risk of bias because the authors did not explain the reason of drop outs
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported. Comment: we considered this low risk of bias
Other bias	High risk	Quote: "the two series of glabellar severity scores were not fully superimposable: taking the objective double‐blind, digital photographic baseline results as a reference, it appears that clinical scoring overestimated the occurrence of medium scores (scores of 2) by including patients with a mild score (score of 1). Conversely, severe scores were slightly underestimated by the investigators." page 227 Comment: to clarify this information an e‐mail was sent on 23 May 2015, we did not receive any answer.