Poewe 2016.

Methods	Randomised, double‐blind, parallel design Randomisation: not adequately described Setting: multicentre (61 centres in 11 countries) Duration: 12 weeks
Participants	369 participants enrolled overall 213 participants enrolled with data contributing to the current review (BtA group = 159; placebo group = 54) % Female: BtA: 64%; placebo: 63% Mean age: BtA: 49 years; placebo: 50 years Mean CD duration: BtA: 7 years; placebo: 6 years Mean CD severity, SD (TWSTRS‐total): BtA: 46, 9; placebo: 47, 9 Inclusion criteria: ≥ 18 years old diagnosed with CD ≥ 18 months before trial enrolment untreated with BtA or BtB in the prior 14 weeks TWSTRS total score at baseline ≥ 30 with subscale scores for severity ≥ 15, disability ≥ 3, and pain ≥ 2 Exclusion criteria: known hypersensitivity to BtA, BtB, or related compounds or components in the study drug formulations diagnosis of isolated anterocollis or retrocollis previous poor response to BtA known requirement for ≥ 300 U of onabotulinumtoxinA injected into the neck muscles, ≥ 12,500 U of BtB or ≥1000 U of abobotulinumtoxinA requirement for injections at body sites other than the neck swallowing or respiratory abnormalities defective neuromuscular transmission or persistent neuromuscular weakness or any condition interfering with TWSTRS scoring a body weight < 45.4 kg previous phenol or alcohol injections into the neck muscles previous myotomy or denervation surgery to the neck/shoulder region limited passive range of motion in the neck region pregnancy
Interventions	BtA: Dysport (abobotulinumtoxinA) Placebo: supplied in a 1‐mL prefilled syringe indistinguishable from the active products Study drug preparation: provided as a freeze‐dried powder containing 500 U of BtA haemagglutinin complex together with 125 µg of human albumin and 2.5 mg of lactose. The powder was reconstituted with 1.1 mL sodium chloride for injection using a glass syringe Muscles injected: administered into 2‐4 neck muscles (levator scapulae, trapezius, sternocleidomastoid, splenius capitis, scalenus (medius and anterior), semispinalis capitis, or longissimus capitis) in a single dosing session according to the physicians’ clinical judgment of the individual’s pattern of dystonic activity EMG guidance: left at discretion of the investigator BtA dose per patient: 500 U
Outcomes	Primary outcome: TWSTRS total score at week 4 Secondary outcomes: TWSTRS total and TWSTRS subscales at weeks 4 and 8 Investigator’s and patient's VAS on symptoms Investigator’s overall treatment success VAS for pain at week 4 CD Impact Profile‐58 score at week 4 Adverse events
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information about the sequence generation process to permit judgement of low or high risk
Allocation concealment (selection bias)	Low risk	Participants and investigators enrolling participants could not foresee assignment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "To maintain blinding, all study treatments were identical in appearance and smell. All injections during the double‐blind phase were prepared by dedicated and trained site personnel who were independent from investigators and had no contact with the investigators performing study assessment or the trial patients"
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Quote: "To maintain blinding, all study treatments were identical in appearance and smell. All injections during the double‐blind phase were prepared by dedicated and trained site personnel who were independent from investigators and had no contact with the investigators performing study assessment or the trial patients"
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	Inclusion of a considerable proportion of non‐naive participants, meaning they may have been able to foresee group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons for missing outcome data unlikely to be related to true outcome
Selective reporting (reporting bias)	Low risk	The study protocol is not available but it is clear that the published reports include all expected outcomes
For‐profit bias	High risk	Quote: "This study was sponsored by Ipsen"
Enriched population – preferential enrolment of positive responders	High risk	Inclusion of a considerable proportion of non‐naive participants, meaning they may have been able to foresee group allocation
Enriched population – exclusion of poor responders	High risk	Exclusion of nonresponsive phenotypes