Jankovic 2011.
Study characteristics | ||
Methods | Randomised, double‐blind, parallel design Randomisation: carried out in blocks of four; RANCODE Setting: multicentre Duration: 20 weeks |
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Participants | 129 participants enrolled (BtA group = 75; placebo group = 34) % Female: BtA: 65%; placebo: 65% Mean age (range): BtA: 61.5 years (SD 11); placebo: 62.6 years (SD 8.7) Mean blepharospasm duration: BtA: 233.2 months; placebo: 278 months Mean blepharospasm severity (SD) using JRS total score: BtA: 5.87 (1.49); placebo: 5.76 (1.23) Inclusion criteria:
Exclusion criteria:
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Interventions | BtA dose, dilution, volume, and injection site were selected based on the last 2 BtA treatments (± 10%) prior to the start of the study, up to a maximum of 50 units per eye. Each participant received only one treatment in each eye. BtA: Xeomin (incobotulinumtoxinA); vials were reconstituted with 0.9% sodium chloride up to 50 units per eye Placebo: matching Study drug preparation: BtA provided in vials by Merz EMG guidance: no |
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Outcomes |
Primary outcome:
Secondary outcomes:
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Notes | Merz Pharmaceuticals GmbH (Frankfurt, Germany) was responsible for the funding, conduct, data collection, and statistical analysis of the study. Authors had full access to all study data. | |
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | ‘Patients were randomised by personnel not involved in other study procedures (…) using RANCODE version 3.6 (IDV, Gauting, Germany) for blockwise randomization (…), ensuring stratification by center.’ |
Allocation concealment (selection bias) | Low risk | Comment: method of concealment not specified |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | ‘Investigators and patients were blinded to the treatment assignment: placebo and incobotulinumtoxinA vials had the same appearance, and neither the investigator nor other medical staff or any subject knew the identity of individual study medication.’ |
Blinding of outcome assessment (detection bias) Objective outcomes | Low risk | ‘JRS (both subscores) and the BSDI assessments were performed at each visit by the same blinded, independent rater, who was not involved in any other trial procedure.’ |
Blinding of outcome assessment (detection bias) Subjective outcomes | Unclear risk |
‘A second investigator was responsible for all other assessments and procedures during the course of the trial.’ Comment: Investigator blinding not specified. Although placebo was identical to intervention, the fact that all of the participants were previously treated with botulinum toxin could have led to a degree of bias. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: post‐randomisation exclusions were low and roughly distributed evenly between groups (BtA group = 5/75; Placebo group = 2/34). The reasons are described and ‘no patient discontinued prematurely because of adverse events or insufficient efficacy’. |
Selective reporting (reporting bias) | Low risk | ‘Efficacy was analyzed using the full analysis set (FAS) population, which included all randomised patients.’ ‘All patients who received the trial medication were included in the descriptive safety analysis.’ Comment: The outcomes mentioned in the study protocol matched the outcomes reported in the study. |
Enriched population ‐ predominant enrolment of positive responders | High risk | Enriched population due to exclusive enrolment of people responsive to previous botulinum toxin treatment. ‘A documented stable therapeutic response to the last 2 consecutive injections with onabotulinumtoxinA.’ |
Enriched population ‐ exclusion of poor responders | Low risk | Exclusion of people known to have poorer response to treatment, such as eyelid ataxia. |
For‐profit bias | High risk | Comment: study funded by Merz Pharmaceuticals GmbH |