Cost effectiveness of guanfacine extended release as an adjunctive therapy to a stimulant compared with stimulant monotherapy for the treatment of attention-deficit hyperactivity disorder in children and adolescents

Abstract

Background: Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in childhood, affecting 3-7% of school-age children in the US and imposing substantial economic burden. Stimulants are considered first-line pharmacological treatment and are the most prescribed treatment for ADHD. However, approximately 30% of children with ADHD do not have an optimal response to a single stimulant and may require adjunctive therapy.

Objective: Our objective was to conduct a cost-effectiveness analysis (CEA) of adding a non-stimulant, guanfacine extended release (GXR), to stimulants versus maintaining existing stimulant monotherapy in the treatment of ADHD in children and adolescents with suboptimal response to stimulant monotherapy.

Methods: A 1-year Markov model was developed to estimate costs and effectiveness from a US third-party payer perspective. Effectiveness was measured by the QALY. The model assumed that patients transitioned among four health states (normal, mild, moderate and severe), defined by the Clinical Global Impression-Severity (CGI-S) scale. Transition probabilities were estimated in an ordered logit model using patient-level data from a multicentre, 9-week, double-blind, placebo-controlled, dose-optimization study, where subjects (n = 461) continued their stable morning stimulant and were randomized to GXR administered in the morning, GXR administered in the evening, or placebo. The model assumed that patients in moderate/severe health states after week 8 would discontinue ADHD treatment and remain in that state for the rest of the study period. Direct costs included drug wholesale acquisition costs and health state costs, all in $US, year 2010 values. Utility associated with each health state was obtained from the literature and disutilities associated with adverse events were applied for the first 4 weeks. One-way sensitivity analyses and probabilistic sensitivity analysis (PSA) were conducted by varying costs, utilities, adverse-event duration, and transition probabilities.

Results: Compared with maintaining existing stimulant monotherapy, adding GXR to existing stimulant monotherapy was associated with an incremental drug cost of $US1016 but a lower medical cost of $US124, resulting in a total incremental cost of $US892 at 1 year. The addition of GXR to stimulants led to an incremental QALY of 0.03 and an incremental cost-effectiveness ratio (ICER) of $US31,660/QALY. In one-way sensitivity analysis, ICER values ranged from $US19,723, when 100% of patients were assumed to be severe in their initial health state, to $US46,631, when the last observed states from the clinical trial were carried forward to the end of the 1-year analysis period. PSA demonstrated a 94.6% likelihood that the ICER falls below $US50,000/QALY.

Conclusions: The impairment associated with residual ADHD symptoms after stimulant therapy is becoming increasingly recognized. This is the first analysis of the cost effectiveness of stimulants combined with an adjunctive medication. This study suggests that the adjunctive therapy of GXR with stimulants is a cost-effective treatment based on a willingness-to-pay threshold of $US50,000/QALY. This may address an unmet need among patients with suboptimal response to stimulant monotherapy.

Fig. 1

Diagram of health states. Patients may enter the model in the mild, moderate or severe states. The data in the tables represent the various transition probabilities. = guanfacine extended release; SE = standard error.

Table I

Key model inputs

Table II

Adverse events^a

Table III

Base-case results

AE

Fig. 2 Univariate sensitivity analysis. The base-case incremental cost-effectiveness ratio is $US31 660/QALY. = adverse event; AWP = average wholesale price; CI = confidence interval; GXR = guanfacine extended release; HCl = hydrochloride; ICER = incremental cost-effectiveness ratio; LOCF = last observation carried forward; WTP = willingness to pay.

Fig. 3

Cost-effectiveness acceptability curve comparing stimulant monotherapy with stimulant and adjunctive therapy of guanfacine extended release. = guanfacine extended release; ICER = incremental cost-effectiveness ratio.