title: Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?
abstract: BACKGROUND
  Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.
  
  
  METHODS
  We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality "wears off").
  
  
  RESULTS
  The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.
  
  
  CONCLUSIONS
  SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker.
authors.affiliation: Department of Surgery, University College London, London, United Kingdom.
authors.forename: Kurinchi S
authors.initials: KS
authors.lastname: Gurusamy
authors.affiliation: Health Economics Group, University of East Anglia, Norwich, United Kingdom ; Cambridge Centre for Health Services Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Edward
authors.initials: E
authors.lastname: Wilson
authors.affiliation: Cochrane Hepato Biliary Group, Granada Hills, California, United States of America.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Koretz
authors.affiliation: Department of Surgery, University College London, London, United Kingdom.
authors.forename: Victoria B
authors.initials: VB
authors.lastname: Allen
authors.affiliation: Department of Surgery, University College London, London, United Kingdom.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
authors.affiliation: Sheila Sherlock Liver Centre and Institute of Liver and Digestive Health, Royal Free Hospital, and UCL, London, United Kingdom.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
authors.affiliation: Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet,Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008954:Models, Biological; D015996:Survival Rate
chemical_list: D000998:Antiviral Agents