Ballantyne 2015

Methods	Type of RCT: 5:2 parallel‐group, double‐blind dose‐ranging RCTs Settings: outpatient care Duration: 24 weeks Start and stop dates: 07/2012 and 05/2013
Participants	Number of participants: 354 Number lost to follow‐up: NA Women: 182 (51%) Age (SD), years: 59 (11) History of CVD: NA Participants with FH: NA Participants with hypercholesterolaemia on stable statin therapy with fasting LDL‐C of 80 mg/dL or more and triglycerides of 400 mg/dL or less
Interventions	Background therapy: statin therapy Randomised therapy: bococizumab (RN316) vs placebo Bococizumab dose: Participants were offered 50 mg, 100 mg, 150 mg once every 2 weeks, or 200 mg, 300 mg every 4 weeks, resulting in a dosage range of 50 mg to 150 mg every 2 weeks Intervention was continued for 24 weeks with dose reduction at day 43 (14‐week regimen) or at day 57 (28‐week regimen)
Outcomes	Adverse events
Notes	Lipid measurement available for 12 weeks of follow‐up NCT01592240
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation by interactive voice‐response system
Allocation concealment (selection bias)	Unclear risk	Unclear how the interactive voice system was implemented
Blinding of participants and personnel (performance bias) LDL‐C	Unclear risk	Although paper and appendix describe the study as double‐blind, it is unclear how this was maintained and who was blinded. However, no LDL‐C measurement was available at/near any of the predefined time points, making this less important
Blinding of outcome assessment (detection bias) LDL‐C	Low risk	Although paper and appendix describe the study as double‐blind, it is unclear how this was maintained and who was blinded. Any lack of blinding of participants and personnel seems unlikely to bias LDL‐C assessment, which was performed in independent laboratories. On the other hand, outcomes such as adverse events may be biased owing to detection bias
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not reported; mixed‐effects models, including baseline measurement, were used for continuous outcomes
Selective reporting (reporting bias)	Unclear risk	Study protocol was unavailable
Other bias	High risk	Funded by Pfizer