Truong 2008.

Study characteristics
Methods	Randomised, double‐blind, placebo‐controlled Randomisation: participants were allocated sequential numbers and randomly assigned to one of the four treatment groups according to a computer‐generated randomisation schedule prepared before study initiation Setting: multicentre (USA only) Duration: 16 weeks
Participants	123 participants enrolled (BtA group = 92; placebo group = 28) Placebo arm: 28 participants (18 dropouts: 64%); 19 participants were female and 9 were male; median age was 62 years (range: 45 to 82); ethnicity: 26 participants were Caucasian, 1 was African‐American, 1 was Asian, none were Hispanic, none were other ethnicity; mean duration of symptoms not stated; mean BDS score at baseline: not stated BtA(Dysport) 40 units/eye: 30 participants (7 dropouts: 23%); 21 participants were female and 9 were male; median age was 66 years (range: 35 to 82); ethnicity: 27 were Caucasian, 1 was African‐American, 1 was Asian, none were Hispanic, none were other ethnicity; mean duration of symptoms not stated; mean BDS score at baseline: not stated BtA(Dysport) 80 units/eye: 31 participants (6 dropouts: 19%); 24 participants were female and 7 were male; median age was 67 years (range: 45 to 80); ethnicity: 28 participants were Caucasian, 2 were African‐American, 1 was Asian, none were Hispanic, none were other ethnicity; mean duration of symptoms not stated; mean BDS score at baseline: not stated BtA(Dysport) 120 units/eye: 31 participants (4 dropouts: 13%); 25 participants were female and 6 were male; median age was 62 years (range: 33 to 91); ethnicity: 24 participants were Caucasian, 1 was African‐American, 1 was Asian, 2 were Hispanic, 2 participants were other ethnicity; mean duration of symptoms not stated; mean BDS score at baseline: not stated Inclusion criteria: bilateral benign essential blapharospasm ‐ defined as a focal dystonia of no known etiology, exhibiting sustained or repetitive involuntary spasm of the muscles of the upper face age ≥ 18 years symptomatic onset at least 6 months before baseline visit minimum score of 8 on the Blepharospasm Disability Scale BtA naive and non‐naive people were accepted, as long as non‐naive were BtA free for at least 12 weeks Exclusion criteria: BtA non‐naive people who had not been BtA free for at least 12 weeks neuroleptic associated blepharospasm; isolated levator dysfunction or eyelid apraxia previous myectomy or neurectomy; people receiving anti‐spastic and muscle‐relaxant medication or neuromuscular joint affecting medication on the 30 days previous to the baseline visit unless taken at a constant dose throughout the study concomitant BtA injections at a site other than the orbicularis oculi muscles people receiving investigational drugs or devices within 30 days prior to the baseline visit, or were expecting to receive such a drug or device over the study period current ophthalmologic infection, a disease of the neuromuscular junction, such as myasthenia gravis or related muscle disorders, or any condition where an intramuscular injection was contraindicated women with a positive urine pregnancy test, who were pregnant or lactating, and those of childbearing potential who were not practicing an efficient method of contraception hypersensitivity to BtA or other components of the test materials, or if they had a history of, or were currently abusing, drugs or alcohol
Interventions	Participants were randomly assigned to one of 4 groups: placebo, 40 units/eye, 80 units/eye, 120 units/eye. The process was completed by an investigator not involved in treatment administration nor participant assessment. A total volume of 0.1 mL of Dysport or placebo was injected subcutaneously in each of the 6 injections sites in the region of the orbicularis oculi muscle. Each participant received only one treatment in each eye. BtA: Xeomin (incobotulinumtoxinA) Placebo: The reconstituted volume of placebo was equivalent to the reconstituted volume for the 120 units study group. Study drug preparation: Dysport (abobotulinumtoxinA) was prepared by reconstituting 500 units of freeze‐dried toxin with 2.5 ml of sodium chloride 0.9% to provide a concentration of 200 units/mL. A volume of reconstitute containing the appropriate number of units per study group (40, 80, or 120 units) was drawn up into a 1.0 mL syringe, which was filled with sodium chloride 0.9% up to a total volume of 0.6 mL EMG guidance: no information
Outcomes	Primary outcome: percentage of normal activity on the Blepharospasm Disability Scale Secondary outcomes: functional disability Frequency on Involuntary Movement scale severity of oculofacial spasms rated using the Severity Rating Scale adverse events
Notes	This study was supported by funding from Ipsen Ltd.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“Eligible patients were allocated sequential numbers before being randomly assigned to one of the four treatment groups according to a computer‐generated randomization schedule prepared before study initiation”
Allocation concealment (selection bias)	Low risk	“A pack containing one vial of study medication (active treatment or placebo, identical in size and appearance) was allocated to each patient. Reconstitution of treatments was prepared by a third party, who was not involved with patient management or assessments”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“A pack containing one vial of study medication (active treatment or placebo, identical in size and appearance) was allocated to each patient. Reconstitution of treatments was prepared by a third party, who was not involved with patient management or assessments. Investigators were blinded to the treatment dose and type of treatment throughout the study"
Blinding of outcome assessment (detection bias) Objective outcomes	Unclear risk	Although all study personnel were stated to be blinded, the high proportion of dropouts in the placebo group (64%) suggests it was possible that the rating investigator identified the treatment group
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	Although all study personnel were stated to be blinded, the high proportion of dropouts in the placebo group (64%) suggests it was possible that the rating investigator identified the treatment group
Incomplete outcome data (attrition bias) All outcomes	High risk	The large proportion of dropouts in the placebo group (64%) might have induced a clinically relevant bias
Selective reporting (reporting bias)	Low risk	The expected outcomes that are usually evaluated in intervention trials for this condition were reported in this study
Enriched population ‐ predominant enrolment of positive responders	Low risk	The inclusion and exclusion criteria do not make any reference to previous response to Botox
Enriched population ‐ exclusion of poor responders	High risk	"Patients were not eligible for inclusion in the study if they had isolated levator dysfunction or eyelid apraxia"
For‐profit bias	High risk	Study funding supported by Ipsen

JRS: Jankovic Rating Scale

BSDI: Blepharospasm Disability Index