Foster 2015a1

Methods	Randomised clinical trial
Participants	558 adult participants Sex: 374 men, 178 women Mean age: 49.5 years Inclusion criteria: chronic hepatitis C genotype 3 who were treatment‐naive or treatment‐experienced, and were required to have liver imaging within 6 months of baseline/Day 1; adults with cirrhosis to exclude HCC , women of childbearing potential (as defined in Appendix 4 must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Baseline/Day 1 prior to randomisation, male participants and female participants of childbearing potential who engage in heterosexual intercourse had to agree to use protocol‐specified method(s) of contraception, lactating women had to agree to discontinue nursing before the study drug was administered, participant had to be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator, participant had to be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments Exclusion criteria: current or prior history of clinically‐significant illness (other than HCV that may interfere with treatment, assessment or compliance with the protocol, screening ECG with clinically significant abnormalities, laboratory results outside of acceptable ranges at screening, pregnant or nursing female or male with pregnant female partner, chronic liver disease of a non‐HCV aetiology (e.g. haemochromatosis, Wilson's disease, alfa‐1 antitrypsin deficiency, cholangitis), infection with HBV or HIV
Interventions	Experimental group: 100 mg of velpatasvir once a day and 400 mg of sofosbuvir once a day for 12 weeks Control group: 400 mg of sofosbuvir plus RBV 1000 or 1200 mg (weight‐based) both for 24 weeks
Outcomes	SVR12, SAE, death, viral resistance
Notes	We could only use data reported at 12 weeks meaning no data were available. We contacted the trial authors for additional information on allocation sequence generation, how many had incomplete outcome data at 12 weeks, SAE, death, health‐related quality of life) at 12 weeks at g.r.foster@qmul.ac.uk on 21 April 2016 but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	An Interactive Web Response System was used
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Described as open‐label
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Described as open‐label
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	There were above 5% dropouts and it was unclear how the trial handled missing participants. It was unclear how many dropouts there were at 12 weeks.
Selective reporting (reporting bias)	Unclear risk	SVR 24 was not reported as described in the prepublished protocol NCT02201953 and supplementary material at NEJM.org
Vested‐interest bias	High risk	The trial was funded by a company that might have an interest in a given result (Gilead Sciences)
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias