Verplancke 2005.

Methods	Randomised controlled trial. Setting: acute general hospital in the UK. Funding: Allergan Inc. and 3M Health Care Ltd.
Participants	Total participants: 35, 71% male, including 20 participants with TBI. Adults: 35, children 0. Serial casting + botulinum toxin A 200 U: total 12 participants, median age 41.5 years; TBI 6 participants. Serial casting + placebo (saline): total 12 participants, median age 33.5 years; TBI 6 participants. Control (physiotherapy): total 11 participants, median age 40 years; TBI 8 participants. Inclusion criteria: participants were screened twice weekly for 4 weeks and their passive range of ankle dorsiflexion was measured in a supine position by a goniometer attached to a multi‐myometer and pressure strain gauge device (MIE Medical Research, Leeds, UK) at a force of 65 N and by the same person, who documented the higher of 2 joint range measurements; unable to achieve 3 degrees of passive ankle dorsiflexion at 65 N of force. Exclusion criteria: pregnant; history of deep vein thrombosis within the previous 12 months; severe lower limb injury or lower limb fracture; previous exposure to continuous muscle relaxants; hypersensitivity to botulinum toxin; received botulinum toxin injections within the previous 3 months. Location of spasticity: lower limb: gastrocnemius and soleus. The authors did not report if the participants had bilateral or unilateral symptoms.
Interventions	Physiotherapy (control): standard programme of physiotherapy, as currently practiced in the neurosciences unit, but were not supplied with sheepskin bootees. Casting and placebo: lower leg casting plus injections with saline into gastrocnemius and soleus muscles, those in casting and placebo were injected with 0.5 mL 0.9% normal saline into each of 4 standard points into gastrocnemius and soleus muscles, giving a total of 4 mL. They were additionally placed in a bespoke 'combicast' made up of Soft Cast and Scotchcast Plus (supplied by 3M Health Care Ltd, Loughborough, UK), which held the lower leg and foot in a neutral plantargrade position, but still allowed soft tissue functioning within the rest of the limb. Casting and botulinum toxin A:  lower leg casting + injections with botulinum toxin A into gastrocnemius and soleus muscles. These participants were placed in casts in the same way as for casting and placebo participants, but were additionally given an injection of botulinum toxin A 200 U (Allergan Pharmaceuticals Inc., Irvine, CA, USA) per leg, equally divided into gastrocnemius and soleus muscles. Each 100‐U vial of botulinum toxin A was diluted.
Outcomes	Outcome assessed at: baseline and 12 weeks. Primary outcomes: spasticity: Modified Ashworth Scale; adverse effect: not listed as an outcome measure, but was reported in the results section. Secondary outcomes: range of movement (ankle); Glasgow Outcome Scale; Glasgow Coma Scale. Length of follow‐up: not reported.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Patients were enrolled in a strict numeric order, but the treatments were randomised in groups of three (i.e., block randomisation in groups of three)."
Allocation concealment (selection bias)	Unclear risk	No Information provided.
Blinding of participants and personnel (performance bias) All outcomes	High risk	"This ensured that blinding of the active (casting +/‐ botulinum toxin A) treatments still occurred and that recruitment produced an even spread of patients within the groups. Blinding the assessor was not possible for control (physiotherapy) patients, as they were not cast. Those treating patients were also blinded." The authors attempted to blind the personnel; however, this was impossible due to some participants not receiving a cast.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The observer was blinded between the active groups, but the absence of a cast in control patients may have biased the findings. This is actually unlikely, as the primary outcome measure was a quantifiable number at a given force and previous data were not available to the assessor for comparison until all the measurements were carried out."
Incomplete outcome data (attrition bias)	Unclear risk	4 participants were withdrawn from the study but it was not reported which groups they from. However, the final measure used in these participants was the 1 taken prior to their exclusion. "In order to prevent fixed contracture formation, patients were withdrawn from the study if they became unable to dorsiflex to > ‐10 degrees. At the time it was considered unethical to continue without using botulinum toxin A and/or casting, and rescue treatment was administered (botulinum toxin injections for groups controls and cast and saline and normal saline injections for cast and botulinum toxin patients). As the assessor continued to be blinded to treatment after rescue treatment was administered, assessment of patients' spasticity continued, but the final measurement prior to exclusion was used for statistical analysis."
Selective reporting (reporting bias)	High risk	All outcomes were reported but no published protocol. No baseline data for the primary outcome (ankle dorsiflexion). No between‐group comparisons for the secondary outcomes.
Baseline Imbalances	Unclear risk	"...patients in the three groups were sufficiently uniform in their characteristics;" however, the authors later stated that, "The patients in all the groups were similar in most respects, but control patients had the smallest range of dorsiflexion at entry and exit."
Appropriate study design (cross‐over trial only)	Low risk	Not relevant, not a cross‐over trial.
Adequate washout period (cross‐over trial only)	Low risk	Not relevant, not a cross‐over trial.
Other bias	Low risk	No concerns noted.

EQ‐5D: EuroQol; FIM: Functional Independence Measure; ITT: intention to treat; SD: standard deviation; SF‐36: 36‐item Short Form; TBI: traumatic brain injury.