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.

Method: 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.

Fig. 1

Diagram of health states. Patients may enter the model in the mild, moderate, or severe states. Adapted from Sikirika et al. 2012

Fig. 2

Results of one-way sensitivity analysis. Results of one-way sensitivity analysis are presented in a Tornado diagram from a Ministry of Health perspective. Lower and upper bounds for considered for the sensibility analysis are indicated on the y-axis for each parameter. The base-case icremental cost-effectiveness ratio is $CA23,720/QALY. AE: adverse event; CI: confidence interval; ICER: incremental cost-effectiveness ratio; LOCF: last observation carried forward; MAS-XR: amphetamine mixed salts; MPH-CR: methylphenidate HCl controlled release; QALY: quality-adjusted life year

Fig. 3

Results of probabilistic sensitivity analysis. Results of probabilistic sensitivity analysis are presented in cost-acceptability curves. Dashed line is from a MoH perspective while solid line is from a societal perspective. The commonly cited threshold in Canada is $CA50,000/QALY. ICER: incremental cost-effectiveness ratio; MoH: Ministry of Health; QALY: quality-adjusted life year