title: Cost effectiveness of guanfacine extended-release versus atomoxetine for the treatment of attention-deficit/hyperactivity disorder: application of a matching-adjusted indirect comparison.
abstract: BACKGROUND
  About 7% of children and adolescents are diagnosed with attention-deficit/hyperactivity disorder (ADHD) in the US. Patients with ADHD who are intolerant of or do not have an optimal response to stimulants often use non-stimulants as alternative therapies. Guanfacine extended-release (GXR) and atomoxetine (ATX) are the only non-stimulants approved by the US Food and Drug Administration for once-daily use in the treatment of children and adolescents with ADHD in the US. ATX has been on the market since 2002 while GXR was recently approved in 2009. To date, there is no comparative effectiveness or cost-effectiveness study comparing the two drugs.
  
  
  OBJECTIVE
  The aim of this study was to assess the cost effectiveness of GXR versus ATX for the treatment of ADHD in children and adolescents, using the comparative efficacy results from a matching-adjusted indirect comparison (MAIC).
  
  
  METHODS
  The MAIC method was used to compare the efficacy between GXR (target dose and lower doses) and ATX (target dose) in the absence of head-to-head clinical trials. Individual patients in the GXR trials were weighted such that the summary baseline characteristics and the efficacy of the placebo arm of the GXR trials matched exactly with those from published ATX trials. After weighting, the efficacy (i.e. change in the ADHD rating scale, fourth edition [ADHD-RS-IV] total score from baseline) was compared between each GXR dosing group and the ATX group. The results from the MAIC analyses were used to populate a 1-year Markov model that is used to compare the cost effectiveness of GXR versus ATX from a US third-party payer perspective. Effectiveness outcomes for each treatment group were estimated as the proportion of responders, defined as patients with ≥25% reduction in ADHD-RS-IV total score from baseline, and average quality-adjusted life years (QALYs). Utilities associated with response/non-response and disutilities due to adverse events were applied in the model. Costs included drug and medical service costs and were inflated to 2011 US dollars ($US). Incremental cost/QALY and incremental cost/responder were estimated. Univariate sensitivity analyses were conducted by varying all model parameters, including costs, utilities, and response rate.
  
  
  RESULTS
  The target dose of GXR was 0.12 mg/kg/day. In match-adjusted populations with balanced baseline characteristics, patients receiving GXR at the dose of 0.09-0.12(p = 0.0016) [DOSAGE ERROR CORRECTED] and 0.075-0.09 mg/kg/day (p = 0.0248) had better efficacy, while those receiving GXR at the dose of 0.046-0.075 mg/kg/day had comparable efficacy (p = 0.0699), compared with patients receiving ATX at the target dose of 1.2 mg/kg/day. In the base case of the cost-effectiveness analysis (CEA), GXR had incremental cost-effectiveness ratios of $US10 637/QALY and $US853/responder, compared with ATX (incremental costs: $US74; incremental effectiveness: 0.007 QALYs and 86 responders per 1000 patients treated). Results of all univariate sensitivity analyses showed that the model results were robust to changes in model inputs.
  
  
  CONCLUSIONS
  To our knowledge, this is the first application of the novel comparative efficacy method of MAIC to a CEA model. The MAIC results indicate that GXR (0.075-0.12 mg/kg/day) was more effective than ATX (1.2 mg/kg/day) in the trial population. The CEA results indicate that GXR is cost effective compared with ATX for the treatment of ADHD in children and adolescents.
authors.affiliation: Shire Development LLC, Wayne, PA 19087, USA.
authors.forename: M Haim
authors.initials: MH
authors.lastname: Erder
authors.forename: Jipan
authors.initials: J
authors.lastname: Xie
authors.forename: James E
authors.initials: JE
authors.lastname: Signorovitch
authors.forename: Kristina S
authors.initials: KS
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Hodgkins
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
authors.forename: Vanja
authors.initials: V
authors.lastname: Sikirica
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000191:economics* / Q000627:therapeutic use; D058647:Adrenergic alpha-2 Receptor Agonists / Q000191:economics* / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000191:economics*; D002648:Child; D003362:Cost-Benefit Analysis; D003692:Delayed-Action Preparations; D005260:Female; D016316:Guanfacine / Q000191:economics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008390:Markov Chains; D011437:Propylamines / Q000191:economics* / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D011437:Propylamines; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride