ODYSSEY COMBO I

Methods	Type of RCT: 1:2 parallel‐group, double‐blind, stratified RCT Settings: outpatient care Duration: 52 weeks Start and stop dates: 07/2012 and 04/2014
Participants	Number of participants: 316 Number lost to follow‐up: 30 Women: 108 (34%) Age (SD), years: 63 (9) History of CVD: 247 (78%) FH participants: 0 Participants with hypercholesterolaemia (LDL‐C ≥ 70 mg/dL) and established CVD or LDL‐C of 100 mg/dL and CHD risk equivalents (e.g. chronic kidney disease) and on a maximally tolerated dose of statin, with possible addition of other lipid‐lowering therapies
Interventions	Background therapy: both add‐on to maximal tolerated dose of statin Randomised therapy: alirocumab vs placebo Alirocumab dose: 104 weeks of 75 mg alirocumab every 2 weeks, with 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 NCT01644175
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Does not mention randomisation but presumably similar as COMBO II: using an interactive voice‐response system
Allocation concealment (selection bias)	Unclear risk	Does not describe this
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	High risk	20 (9.57%) participants in the alirocumab arm had missing lipid measurements compared with 10 (9.34%) in the comparator arm. Potenially, these "missing" participants simply did not make the required follow‐up time (24 weeks) owing to late enrolment; however, without specific description of the reasons for these lower numbers, some concern is warranted
Selective reporting (reporting bias)	Low risk	Reports on protocol‐defined endpoints
Other bias	High risk	Funded by Sanofi and Regeneron