Bronowicki 2013a1

Methods	Randomised clinical trial
Participants	48 adult participants Sex: 35 men, 12 women Mean age: 48.5 years Inclusion criteria: 18‐70 years old with Chronic HCV genotype 1 infection and HCV RNA above 100,000 IU/mL. Participants had no prior treatment or < 4 weeks of total exposure to RBV or peg‐IFN‐based therapy. Participants had to be non‐cirrhotic, documented by liver biopsy obtained within 24 months before randomisation. Exclusion criteria: advanced liver disease, co‐infection with HBC or HIV, hepatocellular carcinoma, other clinical relevant comorbidity. ALT > 5 x the ULN, total bilirubin > 2 mL/dL, albumin < 3.5 g/dL, international normalised ratio > 1.7, platelets < 90x10^9, haemoglobin < 12 g/dL (women) or < 13 g/dL (men).
Interventions	Experimental group 1: oral asunaprevir (200 mg) twice daily for 48 weeks. Experimental group 2: oral asunaprevir (600 mg) twice daily for 48 weeks. Experimental group 3: oral asunaprevir (600 mg) once daily for 48 weeks. Control group: placebo 48 weeks. Co‐intervention: peg‐IFN (subcutaneously at 180 µg/week) and RBV orally twice daily dosed according to body weight.
Outcomes	Proportion of participants with undetectable HCV RNA at week 4 and 12, SAE, AE, mortality, sustained virological response.
Notes	Experimental group 1 vs control. We contacted trial authors on 20 April 2016 for additional information on allocation concealment, specifics of the blinding, what SAE were experienced, and how they dealt with missing data, reached required sample size but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random allocation sequence
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	It was stated that investigators and participants were blinded to treatment assignment throughout the study but it was not stated how the blinding was maintained.
Blinding of outcome assessment (detection bias) All outcomes	High risk	The sponsor was blinded to treatment assignment until the primary end point analysis which was at 12 weeks and we used data at week 24.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	It was unclear how many participants had missing data and how the trial handled participants with missing data
Selective reporting (reporting bias)	Low risk	All outcomes stated in the pre published protocol (NCT01030432) were reported
Vested‐interest bias	High risk	The study was funded by Bristol‐Myers Squibb
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias