Protocol for evaluation of sustained virological response as a surrogate outcome for mortality, decompensated cirrhosis, or hepatocellular carcinoma in people with chronic hepatitis C virus infection treated with direct-acting antivirals

IntroductionSustained virological response (SVR) is commonly used as an indicator of treatment success in people with chronic hepatitis C virus (HCV) infection. However, there is uncertainty on whether SVR is a validated surrogate marker of successful treatment of chronic HCV infection. AimTo evaluate whether SVR is a good surrogate for all-cause mortality, decompensated cirrhosis, or any specific aspect of liver decompensation (jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, or variceal haemorrhage), or hepatocellular carcinoma in people with chronic HCV infection eligible to receive direct-acting antiviral drugs. MethodsO_ST_ABSData sourceC_ST_ABSTwo ongoing systematic reviews on the effectiveness of direct-acting antiviral drugs in chronic HCV infection. AnalysisO_LIEstimate the regression coefficients or between-studies correlation between SVR and the event by three different Bayesian approaches with OpenBUGS, as outlined in the guidance by the Evidence Synthesis Unit (Technical support document 20). C_LIO_LIEstimate the average proportion of the effect mediated through SVR by causal mediation analysis using R. C_LI DiscussionWe will use the German Institute of Quality and Efficiency in Health Care (IQWiG) criterion for surrogacy for cancer and at least 50% of the treatment effect mediated through SVR but will report the information in a way that allows people to interpret the information using their own criteria.