Lawitz 2015

Methods	Randomised clinical trial
Participants	85 adult participants Sex: 68 men, 19 women Mean age: 47 years Countries: USA and Puerto Rico Inclusion criteria: 18–65 years, with treatment‐naive chronic genotype 1–6 HCV infection and HCV RNA levels ≥5 log10 IU/mL at screening. Participants were required to have a BMI of 19–34 kg/m2 inclusive, creatinine clearance > 70 mL/min and QTcF ≤450 ms for men and ≤470 ms for women. Exclusion criteria: co‐infected with HBV or HIV, had prior treatment with a HCV NS5Ainhibitor, evidence of cirrhosis or HCC, history of clinical hepatic decompensation (e.g. ascites, jaundice, encephalopathy or variceal haemorrhage) or any other clinically significant condition other than chronic HCV infection.
Interventions	The trial was divided into 11 dosing cohorts: 5 cohorts of participants with genotype 1a infection; 1 cohort of participants with genotype 1b infection, 1 cohort of participants with genotype 2 infection, 3 cohorts of participants with genotype 3 HCV infection and 1 cohort of participants with genotype 4 HCV infection. Experimental group: oral GS‐5816 (5 mg, 25 mg, 50 mg, 100 mg, 150 mg). Control group: matching placebo.
Outcomes	Safety assessment, efficacy analysis, pharmacokinetic analysis.
Notes	ClinicalTrials.gov number: NCT01740791. The trial reported that 87 participants were randomised, however it was also stated that those with genotype 4 (n = 2) were not randomised. Therefore we could not use data from the combined 150 mg group, as the non‐randomised genotype 4 participants were included in this group. We emailed Lawitz and colleagues on 26 April 2016 for additional information on allocation, blinding, how the trial handled missing data but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central computer‐generated randomisation scheme, by the sponsor
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Matching placebo
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There were more than 5% dropouts and it was unclear how the trial handled missing data.
Selective reporting (reporting bias)	Low risk	All outcomes stated in the protocol were reported on
Vested‐interest bias	High risk	The study was funded by Gilead Sciences
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias