Copeland 2014.

Methods	Method of randomisation: randomisation stratified by the primary goal area (upper limb or lower limb), as described in the previously published study protocol. Sequence generation method not described, but concealed allocation was reported. Blinding: participants, parents, and assessors masked to group allocation Intention‐to‐treat analysis: yes Loss of follow‐up: no Unit of analysis: child
Participants	Place: 1 centre in Australia Period of study: March 2009 to August 2011 Number assigned: 41 Number assessed: 41 23 BoNT‐A group 18 placebo group Inclusion criteria: Children aged 2 to 16 years at study entry Goals primarily concerned with improving ease of care or improving comfort, or both Spasticity in the upper or lower limbs (or both) causing discomfort or increased burden of care, or both Exclusion criteria: Children were excluded if their body weight was under 10 kg or there was a medical contraindication to BoNT‐A Study entry was delayed to ensure that no BoNT‐A injections or orthopaedic surgery had occurred within 6 months or change to oral or other antiplasticity treatment (e.g. intrathecal baclofen) within 2 months of study commencement Age: BoNT‐A group (mean/SD): 7.08/3.58 years Placebo group (mean/SD): 7.41/3.75 years Gender: BoNT‐A group (males/females): 16/7 Placebo group (males/females): 11/7 Motor distribution: Not described, but likely all quadriplegia GMFCS: BoNT‐A group (IV/V): 3/20 Placebo group (IV/V): 0/18
Interventions	BoNT‐A group: Single BoNT‐A injection (onabotulinumtoxinA) into the lower or upper limb muscles (0.5 to 4 U/kg/muscle group) not exceeding 12 U/kg (or total 400 U) Standardised physiotherapy protocol Placebo group: Sham procedure performed with a blunt needle (not penetrating the skin). Injection sites covered with iodine and dressings to ensure blinding. Standardised physiotherapy protocol
Outcomes	Length of follow‐up: Follow‐up of 16 weeks Assessments at baseline, 4 and 16 weeks Primary outcomes: Canadian Occupational and Performance Measure Secondary outcomes: Caregiver Priorities and Child Health Index of Life with Disabilities Care and Comfort Hypertonicity Questionnaire Cerebral Palsy Quality of Life Questionnaire for Children Paediatric Pain Profile
Notes	Comments: The Edwards 2015 report did a detailed safety evaluation of BoNT‐A and included a second cycle where all children received BoNT‐A injections. We did not analyse this cycle in our review. General adverse events data were already presented in the Copeland 2014a report. The detailed analysis provided in the Edwards 2015 report was beyond the scope of this review. Source of funding: supported by Queensland CP Health Service, which received an unrestricted educational grant (10268 to SD and LGP) through the Royal Children’s Hospital Foundation from Allergan Australia. Conflicts of interest: the study authors declare no conflicts of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: sequence generation not clearly described, but the study authors described in their previously published protocol that "randomization would be performed using concealed allocation" (quote), and block randomisation would be done. Likely computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Comment: concealed allocation is described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: participants and parents were masked to group allocation
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: assessors were masked to group allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no incomplete outcome data
Selective reporting (reporting bias)	Low risk	Comment: no selective reporting. The study protocol was previously published and available.
Other bias	Low risk	Comment: no other sources of bias identified