ODYSSEY FH II

Methods	Type of RCT: 2:1 parallel‐group, double‐blind, stratified RCT Settings: outpatient care Duration: 52 weeks Start and stop dates: 12/2012 and 01/2015
Participants	Number of participants: 249 Number lost to follow‐up: 2 Women: 118 (47%) Age (SD), years: 53.2 (17.2) History of CVD: 89 (36%) Participants with FH: 249 (100%) Participants with heFH not adequately controlled with a maximally tolerated daily dose of statin with or without the other LMT, at a stable dose before the screening visit
Interventions	Background therapy: add‐on to maximal tolerated dose of statin and possible addition of other lipid‐lowering therapies Randomised therapy: alirocumab vs placebo Alirocumab dose: 78 weeks 75 mg alirocumab every 2 weeks, with possible uptitration of alirocumab to 150 mg every 2 weeks at week 12. Resulting in a 2‐week equivalent dose of 75 mg to 150 mg
Outcomes	CVD, lipids, any adverse events, all‐cause mortality
Notes	LDL‐C was calculated using the Friedewald formula, or if triglycerides exceeded 400 mg/dL, via the beta quantification method NCT01709500 Subgroup analyses are provided for FH I and FH II combined
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centralised interactive voice‐response system or interactive Web‐response system
Allocation concealment (selection bias)	Low risk	Central allocation
Blinding of participants and personnel (performance bias) LDL‐C	Low risk	Both were blinded
Blinding of outcome assessment (detection bias) LDL‐C	Low risk	Central laboratory
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 (0.60%) portion of the alirocumab arm had missing lipid measurements compared with 1 (1.22%) participant in the comparator arm. Additionally, mixed‐effects (ANCOVA) models were used
Selective reporting (reporting bias)	Low risk	Reports on protocol‐defined endpoints
Other bias	High risk	Funded by Sanofi and Regeneron