Atsukawa 2016.

Study characteristics
Methods	Open‐label randomised clinical trial with parallel‐group design (2 groups)
Participants	Number of participants randomised: 115 participants (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 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 μL; 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. Patients who had not received PEG IFN/ribavirin combination therapy were considered 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 administered subcutaneously at a dose of 180 μg once weekly. Ribavirin was administered orally twice daily, with doses adjusted according to body weight (600 mg daily for < 60 kg, 800 mg daily for 60 to 80 kg, and 1000 mg daily for > 80 kg). Simeprevir was administered 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 participants 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 of 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	Study authors did not report any deaths. "No patient complained of vitamin D‐related symptoms or developed signs of a vitamin D‐related adverse reaction".
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 is likely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding, and outcome measurement is likely to have been 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 was likely to induce bias
Selective reporting (reporting bias)	Unclear risk	Unclear whether all predefined and clinically relevant and reasonably expected outcomes were reported
Other bias	Low risk	Trial appeared to be free of other factors that could put it at risk of bias.