Comella 2011.

Methods	Randomised, double‐blind, parallel design Randomisation: block‐wise randomisation using a software‐generated code Setting: multicentre (37 centres in the USA) Duration: 8 weeks, follow‐up up to 20 weeks
Participants	233 participants enrolled (BtA 120 U group = 78; BtA 240 U group = 81; placebo group = 74) % Female: BtA 120 U: 51%; BtA 240 U: 54%; placebo: 49% Mean age, SD: BtA 120 U: 52.8 years, 11.5; BtA 240 U: 53.2 years, 12.2; placebo: 52.4 years, 10.8 Mean CD duration: BtA 120 U: 9.3 years, 8.4; BtA 240U: 9.7 years, 9.0; placebo: 10.8 years, 9.0 Mean CD severity, SD (TWSTRS total): BtA 120 U: 42.6, 9.7; BtA 240 U: 42.1, 9.3; placebo: 41.8, 7.9 Inclusion criteria: 18‐75 years of age primary CD with predominantly rotational form TWSTRS total score ≥ 20 Exclusion criteria: predominant anterocollis or retrocollis prior CD surgery previous treatment with Bt injections in the last 10 weeks concomitant treatment with phenol, alcohol injections or local anaesthetics in the affected area intrathecal baclofen in the last 2 weeks parenteral use of tubocurarines, barbiturates, aminoglycosides or aminoquinolones Other medications for focal dystonia were required to be on a stable dose for at least 3 months
Interventions	BtA: Xeomin (incobotulinumtoxinA); 120 U or 240 U, diluted in 4.8 mL Placebo: reconstitution of powder with 0.9% NaCl diluted in 4.8 mL Study drug preparation: vials and providers not mentioned Muscles injected: the number of injection sites per muscle and the volume injected into each muscle were determined at the discretion of the investigator EMG guidance: left at discretion of the investigator BtA dose per participant: 120 U or 240 U
Outcomes	Primary outcomes: TWSTRS total (range, 0‐85) at week 4 Secondary outcomes: TWSTRS total and TWSTRS subscales at weeks 4, 8 and final visit PEGR (range, ‐4 to +4; ‐4: marked worsening, +4 complete remission) IGAE (4‐point scale; poor, moderate, good, very good) Adverse events
Notes	Study discontinuations (at week 8), reasons: BtA 120 U: n = 3 (4%), adverse events: n = 1, consent withdrawal: n = 1, lost to F/U: n = 1 BtA 240 U: n = 5 (6%), adverse events: n = 2, consent withdrawal: n = 1, lost to F/U: n = 1, unrelated reasons: n = 1 Placebo: n = 6 (8%), lack of efficacy: n = 3, consent withdrawal: n = 1, lost to F/U: n = 1, unrelated reasons: n = 1
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was performed using RANCODE version 3.6 (IDV, Gauting). Block‐wise randomization by previous treatment with botulinum toxin ensured a balanced treatment assignment for each center for pretreated and treatment‐naïve patients"
Allocation concealment (selection bias)	Unclear risk	Comment: method of concealment not specified
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Subjects, investigators, medical staff, (…) data managers and monitors were blind to subjects' treatment group"
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Quote: "Subjects, investigators, medical staff, biostatisticians responsible for data analysis, data managers and monitors were blind to subjects' treatment group"
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	Comment: although placebo was identical to intervention, the fact that most of the participants had previously been treated with Bt could have led to a degree of bias
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Missing subject data was provided and their absence was regarded according to an ITT protocol" Comment: post‐randomisation exclusions were low and roughly distributed evenly between groups (BtA 120 U group = 3; BtA 240 U group = 5; Placebo group = 6). The reasons for exclusions were described.
Selective reporting (reporting bias)	Low risk	Comment: the outcomes mentioned in the study protocol matched the outcomes reported in the study.
For‐profit bias	High risk	Comment: study funded by Merz Pharmaceuticals GmbH, Frankfurt
Enriched population – preferential enrolment of positive responders	High risk	Quote: "A total of 233 subjects were randomized (...) Of these, 143 were previously treated with botulinum toxin"
Enriched population – exclusion of poor responders	High risk	Quote: "Subjects were excluded if they had (…) predominant anterocollis or retrocollis"