• comparative effectiveness;
  • matching-adjusted indirect comparison;
  • attention-deficit/hyperactivity disorder (ADHD);
  • oppositional defiant disorder (ODD);
  • nonstimulants



To illustrate a matching-adjusted indirect comparison by comparing the efficacy of guanfacine extended release (GXR) and atomoxetine (ATX) in reducing oppositional symptoms in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.


Individual patient data were used from a GXR trial; only published summary data were used from ATX trials. In a matching-adjusted indirect comparison, individual patients from the GXR trial were weighted such that their mean baseline characteristics matched those published for ATX trials. Placebo-arm outcomes were then compared to further assess balance between the matched populations. Changes in the Conners' Parent Rating Scale-Revised Short Form Oppositional Subscale from baseline to endpoint among GXR-treated and ATX-treated patients were then compared.


Before matching, the GXR (n = 143) and ATX (n = 98) trial populations had significant differences in baseline characteristics and placebo-arm outcomes. After matching, baseline characteristics were well balanced across trials, and placebo-arm outcomes became nearly identical. Comparing active treatment arms across the matched populations, GXR was associated with a significantly greater reduction in mean Conners' Parent Rating Scale-Revised Short form oppositional subscale compared with ATX {−5.0 [95% confidence interval (CI): −6.6 to −3.4] vs. −2.4 [CI: −3.7 to −1.1], p = 0.01, effect size = 0.58}.


In the absence of head-to-head randomized trials, matching-adjusted indirect comparisons can provide timely and reliable comparative evidence for decision makers and can be applied even when very few trials are available for the treatments of interest. Copyright © 2012 John Wiley & Sons, Ltd.