Atsukawa 2016.

Methods	Open‐label randomised clinical trial with parallel group design (two groups)
Participants	Number of participants randomised: 115 patients (50% women), aged 31 to 82 years, mean age 64 years, with chronic hepatitis C. Inclusion criteria: HCV genotype 1b as determined by the conventional polymerase chain reaction (PCR)‐based method; IL28B SNP rs8099917 genotype TG or GG (designated as non‐TT); HCV RNA persistently detectable in serum by the real‐time PCR technique; white blood cell count of more than 2000/μ; platelet count of more than 50 000/μL; and haemoglobin levels of more than 9.0 g/dL at the time of enrolment. Patients could participate in the study regardless of whether they had received prior IFN‐based therapy. When patients had not received PEG IFN/ribavirin combination therapy, they were considered as naive patients. Exclusion criteria: Decompensated liver cirrhosis, evidence of other forms of liver disease, presence of malignancy and other serious medical illness, evidence of hypercalcaemia or hyperparathyroidism, positive hepatitis B surface antigen and antibody to HIV type 1, medication with Chinese herbal medicine or other type of vitamin D, past medical history of interstitial pneumonia, pregnancy or possibility of pregnancy, lactating, and past medical history of allergy to biological preparations or antiviral agents.
Interventions	Intervention: lead‐in treatment with oral native vitamin D3 (Healthy Natural Products, Florence, KY, USA) at a dose of 2000 IU once daily for 4 weeks, followed by the addition of the vitamin D3 to the 12‐week triple therapy (PEG IFN‐α‐2a (Roche group‐Chugai, Tokyo, Japan), ribavirin (Chugai) and simeprevir (Janssen, Tokyo, Japan)), followed by 12 weeks of PEG IFN‐ α‐2a and ribavirin (n = 57); Control: 12‐week triple therapy (PEG IFN‐α‐2a (Roche group‐Chugai, Tokyo, Japan), ribavirin (Chugai) and simeprevir (Janssen, Tokyo, Japan)) for 12 weeks, followed by 12 weeks of PEG IFN‐ α‐2a and ribavirin (n = 58). PEG IFN‐α‐2a was administrated subcutaneously at a dose of 180 μg once weekly. Ribavirin was administrated orally twice daily, with doses adjusted according to bodyweight (600 mg daily for <60 kg, 800 mg daily for 60–80 kg and 1000 mg daily for >80 kg). Simeprevir was administrated orally once daily at a dose of 100 mg. Because of the low likelihood of achieving an SVR and high likelihood of developing antiviral resistance, treatment was stopped for patients with serum HCV RNA decline from baseline of less than 3 log IU/mL at 4 weeks of treatment, detectable HCV RNA at 12 weeks of treatment or more than 2 log IU/mL increase in HCV RNA levels from the lowest levels during treatment (defined as viral breakthrough).
Outcomes	Primary outcome: sustainability undetectable viraemia 24 weeks after the end of treatment.
Stated aim of study	To clarify whether native vitamin D3 supplementation could improve SVR rate in PEG‐IFN/ribavirin therapy with simeprevir for people with treatment‐refractory genotype 1b HCV with the IL28B SNP rs8099917 non‐TT.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Used computer‐generated random number table.
Allocation concealment (selection bias)	Unclear risk	Method used to conceal the allocation not described so intervention allocations may have been foreseen before, or during, enrolment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding, and outcome likely to be influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No blinding, and outcome measurement likely to be influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to assess whether missing data in combination with method used to handle missing data were likely to induce bias.
Selective reporting (reporting bias)	Unclear risk	Unclear whether all predefined and clinically relevant and reasonably expected outcomes reported.
For‐profit bias	Unclear risk	Trial may or may not be free of for‐profit bias as no information provided on clinical trial support or sponsorship.
Other bias	Low risk	Trial appeared free of other factors that could put it at risk of bias.