title: Is adjunctive pharmacotherapy in attention-deficit/hyperactivity disorder cost-effective in Canada: a cost-effectiveness assessment of guanfacine extended-release as an adjunctive therapy to a long-acting stimulant for the treatment of ADHD.
abstract: BACKGROUND
  Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada.
  
  
  METHODS
  A Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles.
  
  
  RESULTS
  Over a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11,845/QALY. Probabilistic sensitivity analysis (PSA) of GXR + stimulant showed that it remains a cost-effective strategy in 100 % of the simulations from both perspectives in numerous PSA and one-way sensitivity analyses, relative to a willingness to pay threshold of $50,000/QALY.
  
  
  CONCLUSIONS
  This economic evaluation demonstrates that GXR +  stimulant is cost-effective compared to stimulant alone in the treatment of children and adolescents with ADHD in Canada.
authors.affiliation: Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Station Centre-ville, Montreal, Quebec, H3C 3J7, Canada. jean.lachaine@umontreal.ca.
authors.forename: Jean
authors.initials: J
authors.lastname: Lachaine
authors.affiliation: Shire, 725 Chesterbrook Boulevard, Wayne, PA, 19087, USA. vanja.x.sikirica@gsk.com.
authors.forename: Vanja
authors.initials: V
authors.lastname: Sikirica
authors.affiliation: Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Station Centre-ville, Montreal, Quebec, H3C 3J7, Canada. karine.mathurin@umontreal.ca.
authors.forename: Karine
authors.initials: K
authors.lastname: Mathurin
mesh_terms: D000661:Amphetamine / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000191:economics*; D000697:Central Nervous System Stimulants / Q000191:economics* / Q000627:therapeutic use*; D002648:Child; D003362:Cost-Benefit Analysis; D003692:Delayed-Action Preparations / Q000191:economics / Q000627:therapeutic use; D016527:Drug Costs / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination / Q000191:economics*; D005260:Female; D016316:Guanfacine / Q000191:economics* / Q000627:therapeutic use*; D017048:Health Care Costs / Q000706:statistics & numerical data; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate / Q000627:therapeutic use; D008297:Male; D008390:Markov Chains; D008774:Methylphenidate / Q000627:therapeutic use; D009864:Ontario; D019057:Quality-Adjusted Life Years
chemical_list: D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate; D016316:Guanfacine; D000661:Amphetamine; D000069478:Lisdexamfetamine Dimesylate