title: Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.
abstract: OBJECTIVE
  In the absence of head-to-head randomized trials, indirect comparisons of treatments across separate trials can be performed. However, these analyses may be biased by cross-trial differences in patient populations, sensitivity to modeling assumptions, and differences in the definitions of outcome measures. The objective of this study was to demonstrate how incorporating individual patient data (IPD) from trials of one treatment into indirect comparisons can address several limitations that arise in analyses based only on aggregate data.
  
  
  METHODS
  Matching-adjusted indirect comparisons (MAICs) use IPD from trials of one treatment to match baseline summary statistics reported from trials of another treatment. After matching, by using an approach similar to propensity score weighting, treatment outcomes are compared across balanced trial populations. This method is illustrated by reviewing published MAICs in different therapeutic areas. A novel analysis in attention deficit/hyperactivity disorder further demonstrates the applicability of the method. The strengths and limitations of MAICs are discussed in comparison to those of indirect comparisons that use only published aggregate data.
  
  
  RESULTS
  Example applications were selected to illustrate how indirect comparisons based only on aggregate data can be limited by cross-trial differences in patient populations, differences in the definitions of outcome measures, and sensitivity to modeling assumptions. The use of IPD and MAIC is shown to address these limitations in the selected examples by reducing or removing the observed cross-trial differences. An important assumption of MAIC, as in any comparison of nonrandomized treatment groups, is that there are no unobserved cross-trial differences that could confound the comparison of outcomes.
  
  
  CONCLUSIONS
  Indirect treatment comparisons can be limited by cross-trial differences. By combining IPD with published aggregate data, MAIC can reduce observed cross-trial differences and provide decision makers with timely comparative evidence.
authors.affiliation: Analysis Group, Inc., Boston, MA 02199, USA. jsignorovitch@analysisgroup.com
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.forename: Vanja
authors.initials: V
authors.lastname: Sikirica
authors.forename: M Haim
authors.initials: MH
authors.lastname: Erder
authors.forename: Jipan
authors.initials: J
authors.lastname: Xie
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Paul S
authors.initials: PS
authors.lastname: Hodgkins
authors.forename: Keith A
authors.initials: KA
authors.lastname: Betts
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D057186:Comparative Effectiveness Research / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods