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. 2015 May 29;10(5):e0127237.
doi: 10.1371/journal.pone.0127237. eCollection 2015.

Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate

Jurjen van der Schans  1 , Nikos Kotsopoulos  1 , Pieter J Hoekstra  2 , Eelko Hak  1 , Maarten J Postma  3
Affiliations

Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate

Jurjen van der Schans et al. PLoS One. .

Abstract

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH) formulation may improve drug response and economic efficiency.

Objective: To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.

Methods: A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1) optimal response, (2) sub-optimal response, (3) discontinued treatment, and (4) natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS) and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs). Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.

Results: Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.

Conclusions: This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

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Conflict of interest statement

Competing Interests: PJH has been member of paid advisory board meetings of Shire and Eli Lilly and has received an unrestricted research grant from Shire. MJP has received grants, honoraria and travel stipends from various pharmaceutical companies, inclusive those interested in the subject matter of this paper. JvdS, NK and EH declare that they have no conflict of interest in relation to this work. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Decision tree of the exploratory initial two-month phase prior to the Markov model.
a. Source: Expert panel Faber et al. (2008)[2] b. Source: Expert panel Faber et al. (2008)[2] c. Source: Gau et al. (2008)[17]
Fig 2
Fig 2. Markov model IR-MPH treatment with daily transition probabilities and utilities on an annual basis (QALY).
QALY = Quality adjusted life years a Source: Lloyd et al. (2011) [19] b Source: Wong et al. (2009) [18] c Source: Expert panel Faber et al. (2008) [2] d Source: Faber et al. (2008) [2] e Source: Biederman et al. (2000) [20] f Source: Remaining probabilities
Fig 3
Fig 3. Markov model ER-MPH treatment with daily transition probabilities and utilities on an annual basis (QALY).
QALY = Quality adjusted life years a Source: Lloyd et al. (2011) [19] b Source: Wong et al. (2009) [18] c Source: Expert panel Faber et al. (2008) [2] d Source: Faber et al. (2008) [2] e Source: Steele et al. (2006) [21] f Source: Biederman et al. (2000) [20] g Source: Remaining probabilities
Fig 4
Fig 4. Effect of the univariate sensitivity analyses on the outcome of costs (€) (IR-MPH vs ER-MPH). Illustrative result for ER-MPH, example of MPH-OROS.
tp = transition probability, SR = suboptimal response, OR = optimal response, DT = discontinuing treatment, NR = natural remission, IR-MPH = immediate release methylphenidate, ER-MPH = extended release methylphenidate.
Fig 5
Fig 5. Effect of the scenario analyses on the outcome of costs (€) (IR-MPH vs ER-MPH). Illustrative result for ER-MPH, example of MPH-OROS.
tp = transition probability, SR = suboptimal response, OR = optimal response, DT = discontinuing treatment, NR = natural remission, IR-MPH = immediate release methylphenidate, ER-MPH = extended release methylphenidate.
Fig 6
Fig 6. Effect of the univariate sensitivity analyses on the outcome of effect (QALY) (IR-MPH vs ER-MPH). Illustrative result for ER-MPH, example of MPH-OROS.
tp = transition probability, SR = suboptimal response, OR = optimal response, DT = discontinuing treatment, NR = natural remission, IR-MPH = immediate release methylphenidate, ER-MPH = extended release methylphenidate.
Fig 7
Fig 7. Effect of the scenario analyses on the outcome of effect (QALY) (IR-MPH vs ER-MPH). Illustrative result for ER-MPH, example of MPH-OROS.
tp = transition probability, SR = suboptimal response, OR = optimal response, DT = discontinuing treatment, NR = natural remission, IR-MPH = immediate release methylphenidate, ER-MPH = extended release methylphenidate.
Fig 8
Fig 8. Cost and effect differences of probabilistic sensitivity analysis in cost-effectiveness plane and 95% confidence interval (Illustrative result for ER-MPH, example of MPH-OROS).
QALY = Quality adjusted life years
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