Wissel 2001.
| Methods | Randomised, double‐blind, parallel design Randomisation: method not described Setting: multicentre (Austria and Czech Republic) Duration: 4 weeks, follow‐up up to 16 weeks |
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| Participants | 68 participants enrolled (BtA group = 35; placebo group = 33) % Female: BtA: 46%; placebo: 56% Mean age, SD: BtA: 45.8 years, 13.2; placebo: 49.7 years, 9.6 Mean CD duration, SD: BtA: 6.5 years, 8.0; placebo: 4.8 years, 4.4 Mean CD severity, SD (Tsui scale): BtA: 11.1, 1.7; placebo: 11.5, 1.8 Inclusion criteria:
Exclusion criteria:
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| Interventions |
BtA: Dysport (abobotulinumtoxinA); 500 U, diluted with 1 mL 0.9% saline solution Placebo: 0.125 mg of human serum albumin and 2.5 mg of lactose, diluted with 1 mL 0.9% saline solution Study drug preparation: BtA and placebo provided in vials by Ipsen Muscles injected: based on clinical assessment 2 or 3 muscles were selected for injection: sternocleidomastoid (100 U‐200 U), splenius capitis (250 U‐350 U), trapezius (100 U‐200 U), and levator scapulae (100 U‐200 U). Each muscle was injected in 2 sites EMG guidance: no BtA dose per participant: 500 U |
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| Outcomes |
Primary outcome:
Secondary outcomes:
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| Notes | Participants were withdrawn from the study if they were considered non‐responders at week 4. Participants with an ongoing response at weeks 4 and 8 continued until re‐treatment was required. Study discontinuations (at week 4), reasons: BtA: n = 0 Placebo: n = 0 |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Patients were randomly assigned to receive either placebo or 500 units of Dysport" Comment: insufficient information about the method of randomisation to permit judgement of low risk or high risk |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information to permit judgement of low risk or high risk |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Blinded study medication was supplied (...) as identical vials containing either Dysport (...) or placebo" |
| Blinding of outcome assessment (detection bias) Objective outcomes | Unclear risk | Comment: insufficient information to permit judgement of low or high risk |
| 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: "In order to remove the bias created by the withdrawal of the majority of placebo patients at week 4, a last observation carried forward technique was used for the week 8 analyses" |
| Selective reporting (reporting bias) | Low risk | Comment: the expected outcomes that are usually evaluated in intervention trials for this condition were reported in this study. |
| For‐profit bias | High risk | Quote: "Blinded study medication was supplied by Ipsen Ltd" |
| Enriched population – preferential enrolment of positive responders | High risk | Comment: out of the 68 participants enrolled, 47 had received BtA injections previously |
| Enriched population – exclusion of poor responders | High risk | Quote: "Patients with pure anterocollis were excluded" |
Bt: botulinum toxin BtA: botulinum toxin type A CD: cervical dystonia CDSS: Cervical Dystonia Severity Scale F/U: follow‐up GAS: Global Assessment Scale IGAE: Investigator Global Assessment of Efficacy PEGR: Patient Evaluation of Global Response TWSTRS: Toronto Western Spasmodic Torticollis Rating Scale VAS: visual analogue scale