title: The clinical effectiveness and cost-effectiveness of peginterferon alfa and ribavirin for the treatment of chronic hepatitis C in children and young people: a systematic review and economic evaluation.
abstract: BACKGROUND
  Optimal therapy for children with chronic hepatitis C is unclear. Two treatment regimens are currently licensed in children.
  
  
  OBJECTIVE
  To assess the clinical effectiveness and cost-effectiveness of peginterferon alfa-2a (Pegasys®, Roche) and peginterferon alfa-2b [ViraferonPeg®, Merck Sharp & Dohme (MSD)] in combination with ribavirin (RBV), within their licensed indications, for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3-17 years.
  
  
  METHODS
  Twelve electronic bibliographic databases, including The Cochrane Library, MEDLINE and EMBASE, were searched from inception to November 2012. Bibliographies of retrieved papers, key hepatitis C websites and symposia and manufacturers' submissions to the National Institute for Health and Care Excellence were also searched, and clinical experts were contacted.
  
  
  METHODS
  Systematic reviews of clinical effectiveness and cost-effectiveness were conducted, including studies of health-related quality of life (HRQoL), following standard guidelines to ensure methodological rigour. Clinical effectiveness studies were included if they were in children and young people aged 3-17 years with chronic compensated HCV of any severity, including those with human immunodeficiency virus co-infection and those who were treatment naive or had been previously treated. Eligible interventions were peginterferon alfa-2a or peginterferon alfa-2b, each in combination with RBV, compared against best supportive care (BSC) or against each other, and study designs were randomised controlled trials (RCTs) or non-RCTs, or uncontrolled cohort studies. Outcomes included sustained virological response (SVR) and adverse events. Previously published Markov state-transition economic models of chronic HCV in adults were adapted to estimate the cost-effectiveness of peginterferon alfa-2a and -2b (in combination with RBV), compared with BSC and with one another in children. The model extrapolated the impact of SVR on life expectancy, quality-adjusted life expectancy and lifetime costs. Uncertainty was explored through probabilistic and deterministic sensitivity analyses.
  
  
  RESULTS
  Seven studies [two peginterferon alfa-2a and RBV (Copegus®, Roche), and five peginterferon alfa-2b and RBV (Rebetol®, MSD)] were included in the review of clinical effectiveness. Six were single-arm cohort studies and one was a RCT for which only those data for a single arm met the inclusion criteria. Overall, the studies were relatively small and of generally poor quality. SVR rates ranged from 53% to 66% (peginterferon alfa-2a) and 29% to 75% (peginterferon alfa-2b) (49% to 65% if excluding two studies with very small sample sizes). Rates of non-response and relapse were variable and adverse events were generally mild. No studies of cost-effectiveness or HRQoL in children and young people met the inclusion criteria. HRQoL, utilities and costs of treatment were therefore taken from studies of adults with chronic HCV. From this model, peginterferon alfa (-2a or -2b) in combination with RBV was more effective and had lower lifetime costs than BSC. Peginterferon alfa-2a had slightly lower lifetime costs and higher quality-adjusted life-years than peginterferon alfa-2b; therefore, peginterferon alfa-2b was dominated by peginterferon alfa-2a. Results were robust to changes in the sensitivity analyses.
  
  
  CONCLUSIONS
  There were few good quality studies and parameter data had to be taken from adult studies, which is a limitation of the work.
  
  
  CONCLUSIONS
  Treatment of children and young people with peginterferon (alfa-2a or -2b) and RBV may be an effective therapy. Results from the independent Markov model suggest that peginterferon (alfa-2a or -2b) in combination with RBV is cost-effective compared with BSC. However, the available evidence is of poor quality. Future research into the impact of these treatments on growth and quality of life in children and young people is recommended.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42012002743.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: Hartwell
authors.affiliation: Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Cooper
authors.affiliation: Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK.
authors.forename: Geoff K
authors.initials: GK
authors.lastname: Frampton
authors.affiliation: Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Baxter
authors.affiliation: Southampton Health Technology Assessments Centre (SHTAC), University of Southampton, Southampton, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Loveman
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D015415:Biomarkers; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000191:economics / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D008297:Male; D008390:Markov Chains; D017059:Models, Econometric; D011092:Polyethylene Glycols / Q000191:economics / Q000627:therapeutic use; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012367:RNA, Viral; D011994:Recombinant Proteins / Q000191:economics / Q000627:therapeutic use; D012254:Ribavirin / Q000191:economics / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a