Ogilvie 2019.

Study characteristics
Methods	Study design‐ multicentre, randomised, double‐blind, placebo‐controlled, parallel ‐design,phase III in glabellar lines (Period 1) and an open‐label extension (period 2) Study date‐ Start October 2014. Finished April 2016 Study setting‐ outpatients from 16 centres (9‐USA, 5‐Canada, 2‐Europe)
Participants	Randomised 391 participants. Age 44.5 ±11.2 Onabotulinum group and 42.4 ±10.6 placebo group. Gender 85.9% female in OnabotulinumtoxinA group and 86.1% in placebo group. Inclusion criteria Botulinum toxin–naive men and women aged at least 18 years Moderate to severe FHL at maximum eyebrow elevation, as evaluated by the investigator Exclusion criteria Any uncontrolled systemic disease, marked periocular or eyebrow asymmetry Marked dermatochalasis Deep dermal scarring, excessively thick sebaceous skin Eyebrow or eyelid ptosis, eyelid folds reaching the pupil or touching the upper lash line Known immunisation to any botulinum toxin serotype, or anticipated need for botulinum toxin treatment for another indication during the study Had ever undergone prior periorbital, midfacial, or upper facial treatment with permanent soft‐tissue fillers, synthetic implant placement, autologous fat transplantation, surgery   Ethnicity: Caucasian 89.7% in OnabotulinumtoxinA group and 86.1% in placebo group. Asian 3.1 in OnabotulinumtoxinA group and 5% in placebo. Others 7.2% in OnabotulinumtoxinA group and 8.9% in placebo group. Severity of the disease:(maximum frown):Moderate 47.6% in OnabotulinumtoxinA group and 47.5% in Placebo group. Severe 52.4 % in OnabotulinumtoxinA group and 52.4% in Placebo group.
Interventions	Duration:Period 1‐ 6 months. Period 2‐6 months Intervention OnabotulinumtoxinA 40 U (20 U in FHL and 20 U in GL) administered at 10 injection sites Comparator Placebo same volume in FHL and in GL) administered at 10 injection sites Ratio: 3:1 (OnabotulinumtoxinA: placebo)
Outcomes	Primary outcome Proportion of mostly or very satisfied patients Secondary outcomes Responders rate of FLSQ Impact domain Responders rate FLO‐11item 1, item 4, item 5, and total score
Notes	This study was funded by Allergan plc, Dublin, Ireland. Editorial support for this article was provided by Peloton Advantage, Parsippany, New Jersey, and was funded by Allergan plc. P. Ogilvie has received research support or speaking/consultant fees from Allergan plc, Evolus, Inc., Galderma, Merz Aesthetics, and Revance. A.Z. Rivkin serves as a consultant and investigator for Allergan plc and Merz Aesthetics.  S. Dayan has received research support or speaking/consultant fees from Allergan plc, Galderma, Merz Aesthetics, and Valeant. S.G. Yoelin serves as a consultant and investigator for Allergan plc. B.M. Weichman was employed by Peloton Advantage, which received funding from Allergan plc for medical editing and editorial support. J.K. Garcia is an employee of Allergan plc and owns stock/options in the company. The opinions expressed in this article are those of the authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote:"The randomization assignment was obtained from an interactive voice/web response system, which was based on a randomization scheme prepared by Allergan Biostatistics"...Page3 Comment: we consider a low risk of bias
Allocation concealment (selection bias)	Low risk	Quote:"The randomization assignment was obtained from an interactive voice/web response system, which was based on a randomization scheme prepared by Allergan Biostatistics"...Page3 Comment: we consider a low risk of bias
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote:The study comprised a 6‐month, double‐blind,placebo‐controlled"...Page 3 Comment: we consider unclear bias because the authors did not mention how they blinded the participants and staff
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote:The study comprised a 6‐month, double‐blind,placebo‐controlled"...Page 3 Comment: we consider unclear bias because the authors did not mention how they blinded the participants and staff
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote:"early discontinuations were mostly attributable to personal reasons or being lost to follow‐up (Figure 2...Page4 Comment: we consider unclear risk of bias because the authors did not mention the reasons of the drop‐out
Selective reporting (reporting bias)	Low risk	All prespecified outcomes were reported Comments: we consider low risk of bias
Other bias	Unclear risk	One of the authors was an employee of the sponsor