title: Indirect comparison of the antiviral efficacy of peginterferon alpha 2a plus ribavirin used with or without simeprevir in genotype 4 hepatitis C virus infection, where common comparator study arms are lacking: a special application of the matching adjusted indirect comparison methodology.
abstract: BACKGROUND
  The need to assess relative efficacy in the absence of comparative clinical trials is a problem that is often encountered in economic modeling. The use of matching adjusted indirect comparison (MAIC) in this situation has been suggested. We present the results of a MAIC used to evaluate the incremental benefit offered by adding simeprevir (SMV) to standard therapy in the treatment of patients infected with genotype 4 hepatitis C virus (HCV).
  
  
  METHODS
  Individual patient data for a single arm study evaluating the use of SMV with peginterferon alfa 2a + ribavirin (PR) in genotype 4 HCV were available (RESTORE study). A systematic literature review was used to identify studies of PR alone used in the same patient group. By applying the inclusion criteria for each study in turn to the RESTORE dataset and then applying the published MAIC covariate matching algorithm, a series of pseudosamples from RESTORE were generated. After assessment of the matching outcomes, the best matched comparisons were used to derive estimates of efficacy for SMV + PR in patients equivalent to those participating in the PR trial.
  
  
  RESULTS
  Five potential comparator studies were identified. After applying the matching process, two emerged as offering the greatest equivalence with the generated RESTORE pseudosamples and were used to estimate SMV + PR efficacy, expressed as the percentage of patients achieving sustained viral response (SVR). In one comparison, SVR in the SMV + PR group was 85% versus 63% for PR alone. In the second comparison, the corresponding SVRs were 77% and 44% respectively.
  
  
  CONCLUSIONS
  After matching for varying baseline characteristics, both comparisons of RESTORE versus studies of PR alone yielded a benefit for SMV + PR vs PR alone in genotype 4 HCV-infected patients. The incremental gain in SVR associated with use of SMV ranged from 22% to 33%. In the absence of direct comparative studies, the MAIC gives a better perspective than simple comparison of absolute SVR from individual studies.
authors.affiliation: a a Janssen Pharmaceutica NV , Beerse , Belgium.
authors.forename: Suzy
authors.initials: S
authors.lastname: Van Sanden
authors.affiliation: a a Janssen Pharmaceutica NV , Beerse , Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Pisini
authors.affiliation: a a Janssen Pharmaceutica NV , Beerse , Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Duchesne
authors.affiliation: b b Janssen-Cilag GmbH , Neuss , Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Mehnert
authors.affiliation: c c JB Medical Ltd , Sudbury , UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Belsey
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D000069616:Simeprevir / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a
keywords: Genotype 4 hepatitis C virus; HCV infection; MAIC; Matching adjusted indirect comparison; Peginterferon alpha 2a + ribavirin; Simeprevir