title: Systematic Review of Modelling Approaches for the Cost Effectiveness of Hepatitis C Treatment with Direct-Acting Antivirals.
abstract: New direct-acting antivirals (DAAs) are highly effective for hepatitis C virus (HCV) treatment. However, their prices have been widely debated. Decision-analytic models can project the long-term value of HCV treatment. Therefore, understanding of the methods used in these models and how they could influence results is important.
  
  
  
  Our objective was to describe and systematically review the methodological approaches in published cost-effectiveness models of chronic HCV treatment with DAAs.
  
  
  
  We searched several electronic databases, including Medline, Embase and EconLit, from 2011 to 2015.
  
  
  
  Study selection was performed by two reviewers independently. We included any cost-effectiveness analysis comparing DAAs with the old standard of care for HCV treatment. We excluded non-English-language studies and studies not reporting quality-adjusted life-years.
  
  
  
  One reviewer collected data and assessed the quality of reporting, using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Another reviewer crosschecked the abstracted information. The development methods of the included studies were synthetized on the basis of good modelling practice recommendations.
  
  
  
  Review of 304 citations revealed 36 cost-effectiveness analyses. The reporting quality scores of most articles were rated as acceptable, between 67 and 100 %. The majority of the studies were conducted in Europe (50 %), followed by the USA (44 %). Fifty-six percent of the 36 studies evaluated the cost effectiveness of HCV treatment in both treatment-naive and treatment-experienced patients, 97 % included genotype 1 patients and 53 % evaluated the cost effectiveness of second-generation or oral DAAs in comparison with the previous standard of care or other DAAs. Twenty-one models defined health states in terms of METAVIR fibrosis scores. Only one study used a discrete-event simulation approach, and the remainder used state-transition models. The time horizons varied; however, 89 % of studies used a lifetime horizon. One study was conducted from a societal perspective. Thirty-three percent of studies did not conduct any model validation. We also noted that none of the studies modelled HCV treatment as a prevention strategy, 86 % of models did not consider the possibility of re-infection with HCV after successful treatment, 97 % of studies did not consider indirect economic benefits resulting from HCV treatment and none of the studies evaluating oral DAAs used real-world data.
  
  
  
  The search was limited by date (from 1 January 2011 to 8 September 2015) and was also limited to English-language and published reports.
  
  
  
  Most modelling studies used a similar modelling structure and could have underestimated the value of HCV treatment. Future modelling efforts should consider the benefits of HCV treatment in preventing transmission, extra-hepatic and indirect economic benefits of HCV treatment, real-world cost-effectiveness analysis and cost effectiveness of HCV treatment in low- and middle-income countries.
authors.affiliation: Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, 101 Merrimac Street, 10th Floor, Boston, MA, 02114, USA. jagchhatwal@mgh.harvard.edu.
authors.forename: Jagpreet
authors.initials: J
authors.lastname: Chhatwal
authors.affiliation: Tsinghua University School of Medicine, Beijing, China.
authors.forename: Tianhua
authors.initials: T
authors.lastname: He
authors.affiliation: Department of General Internal Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lopez-Olivo
mesh_terms: D000998:Antiviral Agents / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D018803:Models, Economic; D019057:Quality-Adjusted Life Years
chemical_list: D000998:Antiviral Agents