Bertucci 2020.

Study characteristics
Methods	Study design‐ multicentre, randomised, double‐blinded, placebo‐controlled, parallel‐design. Phase III in glabellar lines (SAKURA 1 and SAKURA 2). NCT03014622 and NCT03014635 Study date‐started December 5, 2016, and ended on 14 November 2017 Study setting‐ outpatients, 30 centres (24 in the USA and 6 in Canada
Participants	Randomised 609 participants with age range 50.2 ± 10.56 years in DaxibotulinumtoxinA group, and 49.8 ±10.58 years in placebo group. Gender 335/405(88.1%) females in DaxibotulinumtoxinA group, and 175/204 (85.8%) in placebo group. Prior treatment‐ 213/405(52.6%) in DaxibotulinumtoxinA group and 105/204(51.5%) in placebo group. Inclusion criteria Provide written informed consent including authorisation to release health information Moderate (2) or severe (3) glabellar lines during maximum frown based on the Investigator Global Assessment Frown Wrinkle Severity (IGA‐FWS) scale Moderate (2) or severe (3) glabellar lines during maximum frown based on the Patient Frown Wrinkle Severity (PFWS) scale Willing and able to follow all trial procedures, attend all scheduled visits, and successfully complete the trial Exclusion criteria Any neurological condition that may place the participant at increased risk with exposure to botulinum toxin type A, including peripheral motor neuropathic diseases such as amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert‐Eaton syndrome and myasthenia gravis Active skin disease, infections or inflammation at the injection sites Plan to receive botulinum toxin type A anywhere in the face through the duration of the study History of allergy or sensitivity to any botulinum toxin preparations or to any component of the test article Current enrolment in an investigational drug or device trial or participation in such a trial within the last 30 days prior to screening through end of trial Severity of the disease‐ moderate 252/405(62.2%) in DaxibotulinumtoxinA group, and 133/204(65.2%) in placebo group. Ethinicity‐ caucasian 353/405 (87.2%),19/405(4.7%) African American, 18/405 (4.4%) Asian, 15/405 (3.7%) other in DaxibotulinumtoxinA group; Caucasian 173/204 (87.4.8%),11/204(5.4%) African American, 7/204 (3.4%) Asian, 13/204 (6.4%) other in
Interventions	Duration: 36 weeks Intervention DaxibotulinumtoxinA 40 U, (N = 405), two 0.1‐mL injections into each corrugator muscle and one 0.1‐mL injection into the procerus muscle. Intramuscular injection in glabella region Comparator Placebo (N = 204), two 0.1‐mL injections into each corrugator muscle and one 0.1‐mL injection into the procerus muscle.Iintramuscular injection in glabella region.
Outcomes	Primary outcomes Proportion of participants who achieve the following status concurrently at Week 4: A score of 0 or 1 (i.e. none or mild wrinkles in severity) on both IGA‐FWS and PFWS assessments; At leas tone‐point improvement from baseline on both IGA‐FWS and PFWS assessments [Time Frame: Week 4] Secondary outcomes Proportion of participants who achieve a score of ≥ 1 on the investigator's assessment of GAIS [Time Frame: From Week 2 to Week 24] Proportion of participants who achieve a score of ≥ 1 on the participant's self‐assessment of GAIS [Time Frame: From Week 2 to Week 24] Duration of the treatment Adverse events
Notes	"We thank Revance Therapeutics, Inc, for sponsoring the studies and funding the development of the manuscript."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote:"An independent statistician produced a computer‐generated randomization code (using SAS PROC PLAN [SAS Institute, Inc, Cary, NC])...page 840 Comment: we considered this low risk of bias
Allocation concealment (selection bias)	Low risk	Quote:" Study treatments were provided in sequentially numbered clinical trial kits containing single use 50‐U vials,"... page 840
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote:"All vials looked identical to each other before and after reconstitution"...page 840 Comment: we considered this low risk of bias
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote:"All vials looked identical to each other before and after reconstitution"...page 840 Comment: we considered this low risk of bias
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote:"Discontinuations were attributable predominantly to withdrawal of consent and loss to follow‐up, with none being due to adverse events (Supplemental Fig 1)...page 841 Comment: we considered this low risk of bias
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported Comment: we consider low risk of bias
Other bias	Low risk	Pharmaceutical sponsored