Manns 2012a1

Methods	Randomised clinical trial
Participants	95 participants were randomised Sex: 55 men, 39 women Mean age: 46.2 years Inclusion criteria: adult, treatment‐naive participants with chronic, compensated, HCV genotype 1 infection, defined as HCV RNA levels ≥ 4 × 105 IU/mL at screening (i.e. within 75 days preceding the first dose of vaniprevir or placebo), were enrolled. All participants had positive serology for HCV or detectable HCV RNA ≥ 6 months before study initiation. Exclusion criteria: Participants with evidence of cirrhosis by histology, imaging, or physical findings were excluded.
Interventions	Experimental group: 300 mg twice a day plus open‐label peg‐IFN α‐2a and RBV 180 μg/week + 1000 mg‐1200 mg/day for 28 days. 600 mg twice a day plus open‐label peg‐IFN α‐2a and RBV 180 μg/week + 1000 mg‐1200 mg/day for 28 days. 600 mg once a day plus open‐label peg‐IFN α‐2a and RBV 180 μg/week + 1000 mg‐1200 mg/day for 28 days. 800 mg once a day plus open‐label peg‐IFN α‐2a and RBV 180 μg/week + 1000‐1200 mg/day for 28 days. Control group: placebo plus open‐label peg‐IFN α‐2a and RBV 180 μg/week + 1000 mg‐1200 mg/day for 28 days. Co‐intervention: peg‐IFN α‐2a and RBV 180 μg/week + 1000 mg‐1200 mg/day.
Outcomes	Primary: proportion of participants achieving RVR. AEs and participants that discontinued due to AEs. Exploratory: proportion of participants achieving EVR, proportion of participants achieving SVR.
Notes	We emailed Manns and colleagues on 26 April 2016 for additional information on allocation concealment, unpublished data, correlation of il28b genotype data and SVR but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central randomisation procedure by an interactive voice‐response system
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The study was described as double‐blinded to investigator and participant
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	The study was described as double‐blinded but it was unclear how the blinding was maintained and who performed the outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	15 participants dropped out
Selective reporting (reporting bias)	Unclear risk	A protocol was found (NCT00704184), primary objectives were reported correctly, secondary outcomes changed and new exploratory outcomes were reported in the paper
Vested‐interest bias	High risk	This study was funded by Merck Scharp and Dohme Corp.
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias