Nelson 2012b

Methods	Randomised clinical trial
Participants	323 adult participants Inclusion criteria: chronic HCV infection for at least 6 months prior to baseline (Day 1), liver biopsy results (performed no more than 2 years prior to screening) indicating the absence of cirrhosis, mono‐infection with HCV genotype 1a or 1b, HCV treatment‐naive, BMI between 18 and 36 kg/m2, creatinine clearance >/= 50 mL/min, participant agreed to use highly effective contraception methods if female of childbearing potential or sexually active male, screening laboratory values within defined thresholds for ALT, AST, leukopenia, neutropenia, anaemia, thrombocytopenia, thyroid stimulating hormone, potassium, magnesium. Exclusion criteria: autoimmune disease, decompensated liver disease or cirrhosis, poorly controlled diabetes mellitus, severe psychiatric illness, severe chronic obstructive pulmonary disease, serological evidence of co‐infection with HIV, HBV, or another HCV genotype, suspicion of HCC or other malignancy (with exception of certain skin cancers), history of haemoglobinopathy, known retinal disease. participants who were immunosuppressed, participants with known, current use of amphetamines, cocaine, opiates (i.e. morphine, heroin), methadone, or ongoing alcohol abuse, participants who were on or are expected to be on a potent cytochrome P450 (CYP) 3A4 or Pgp inhibitor, or a QT prolonging medication within 2 weeks of baseline (Day 1) or during the study, participants must have had no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant ECG abnormalities at screening.
Interventions	Experimental group 1: tegobuvir (20 mg twice a day) + GS‐9256 (150 mg twice a day). Experimental group 2: GS‐9256 (150 mg twice a day). Control group: placebo. Co‐intervention: Peg (180 mg/week) + RBV (1000–1400 mg/day).
Outcomes	Safety, SVR12 (not fully reported so could not be used).
Notes	Participants receiving the 4‐drug therapy who achieved an extended vRVR were randomised to stop treatment at either Week 16 or Week 24. We contacted the trial authors on 06 June 2016 for additional information allocation sequence generation, blinding, dropouts and how this was handled, primary publication, SAE, death, SVR24, number of participants randomised to each group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Described as double blind but the placebo was not further described
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	It was unclear how many participants dropped out
Selective reporting (reporting bias)	High risk	Not all predefined outcomes in the protocol were reported on (viral resistance, SVR24)
Vested‐interest bias	High risk	The trial was supported 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