|Long-acting methylphenidate-OROS in youths with attention-deficit hyperactivity disorder suboptimally controlled with immediate-release methylphenidate: a study of cost effectiveness in the Netherlands
|Faber A, van Agthoven M, Kalverdijk L J, Tobi H, de Jong-van den Berg L T, Annemans L, Postma M J
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
This study examined the cost-effectiveness of long-acting methylphenidate osmotic release oral system (OROS) for the treatment of young people (8 to 18 years) with attention deficit hyperactivity disorder, for whom treatment with immediate-release (IR) methylphenidate was effective, but sub-optimal due to problems with multiple daily administration. The authors concluded that OROS methylphenidate was cost-effective compared with IR methylphenidate. The methodology was valid and the study was well presented, especially the economic details. The authors’ conclusions appear to be robust.
Type of economic evaluation
This study examined the cost-effectiveness of long-acting methylphenidate osmotic release oral system (OROS) for the treatment of young people (8 to 18 years) with attention deficit hyperactivity disorder (ADHD), for whom treatment with immediate-release (IR) methylphenidate was effective, but sub-optimal due to problems with the multiple daily administration regimen.
The two treatments were OROS methylphenidate (once daily) versus IR methylphenidate (three times daily).
This economic evaluation was based on a Markov model with a 10-year time horizon. The authors stated that the analysis was conducted from the perspective of society or the community.
The clinical data came from a selection of known sources including a randomised controlled trial (RCT), a database that covered all prescriptions from an estimated population of approximately 450,000 people in the Netherlands, and a published study the details of which were not given. Most of the data, however, were derived from a panel consisting of three paediatricians and two child psychiatrists with expertise in ADHD. The key clinical endpoint was the probability of functional remission, which was assumed to be similar between treatments.
Monetary benefit and utility valuations:
The utility valuations were derived from a UK study that used 83 parents of patients as a proxy, using the standard gamble method. Some assumptions were also made for a few health states.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure and were discounted at an annual rate of 4%.
The economic analysis included the costs of medications (acquisition and pharmacy fee), consultations (specialist, general practitioner, and crisis contact), treatment interventions (psycho-education, parent training, behavioural therapy, social skills training, teacher training, remedial teaching, home training, out-patient treatment, and institutionalisation), and additional costs for attending special education. The resource use was derived from the panel of experts. The unit costs were presented for all items and were derived from official Dutch sources. Costs were in Euros (EUR) for the price year 2005. Future costs were discounted at an annual rate of 4%.
Analysis of uncertainty:
A series of one-way sensitivity analyses was carried out on all the model inputs, including the time horizon. A worst- and best-case scenario were also considered.
The expected 10-year costs were EUR 15,739 with IR methylphenidate and EUR 16,015 with OROS methylphenidate. The QALYs were 7.66 with IR and 7.79 with OROS methylphenidate. Thus, under base-case conditions, the incremental cost per QALY gained with OROS over IR methylphenidate was EUR 2,004.
The most influential model inputs were resource use in the optimal and sub-optimal response states, and the probability of stopping IR methylphenidate versus OROS methylphenidate. The cost of OROS methylphenidate was another influential input.
In the worst-case scenario, the incremental cost per QALY gained was EUR 38,363. In the best-case scenario, OROS methylphenidate was simultaneously less expensive and more effective than IR methylphenidate.
The authors concluded that OROS methylphenidate was a cost-effective alternative to IR methylphenidate for young people with ADHD for whom treatment with IR methylphenidate was not optimal. The authors stated that future studies should provide more reliable inputs for the model to assess the societal impact of ADHD and its treatment.
The selection of the comparators appears to have been appropriate, since the two available formulations of the most commonly used stimulant for ADHD were compared.
The authors selected the sources of clinical data, which were presumably considered to be the most appropriate for the study. A RCT is considered to be a valid source of evidence on treatment efficacy, given the strengths of its design. Similarly, the use of a large database reflected treatment patterns in the authors’ setting. Expert opinions supplemented the published evidence, which might introduce bias and uncertainty into the clinical inputs, as the authors acknowledged. However, the authors investigated the impact of variations in the clinical inputs on the findings and identified the most critical inputs, which showed that the model was generally robust. The derivation of the utility values used to calculate the QALYs was partially described. In general, QALYs are an appropriate benefit measure of the impact of the treatments on quality of life. They enhance the external validity of the analysis.
The categories of costs may not have fully reflected the perspective stated. Extensive information on the cost calculation was provided. The use of a panel of experts to derive the resource use was justified by the lack of reliable published evidence. Quantities of resources used were presented separately from unit costs for most items. Other details such as the price year, use of discounting, assumptions made in the assessment of resources, and sources of data were reported. In general, the economic analysis was carried out in a credible fashion. The authors noted that the inclusion of indirect costs or direct non-medical costs was not attempted due to the lack of reliable estimates. Other studies had shown that the inclusion of these costs would not have altered the conclusions of the base-case analysis.
Analysis and results:
The synthesis of costs and benefits was based on an incremental approach. The issue of uncertainty was addressed using a deterministic analysis, but the multivariate approach should have ensured a comprehensive evaluation of all uncertain aspects of the model. The findings of both the base case and the sensitivity analyses were clearly presented and discussed. The authors pointed out that their findings applied to the specific subgroup of patients for whom IR methylphenidate was not optimal as a result of administration problems, and that they should not be generalised to other ADHD patients.
The study was based on valid methodology and was well presented, especially the economic details. The authors’ conclusions appear to be robust.
Supported by Janssen Cilag BV, The Netherlands.
Faber A, van Agthoven M, Kalverdijk L J, Tobi H, de Jong-van den Berg L T, Annemans L, Postma M J. Long-acting methylphenidate-OROS in youths with attention-deficit hyperactivity disorder suboptimally controlled with immediate-release methylphenidate: a study of cost effectiveness in the Netherlands. CNS Drugs 2008; 22(2): 157-170
Other publications of related interest
Steele M, Weiss M, Swanson J, et al. A randomized, controlled, effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention-deficit-hyperactivity-disorder. Can J Clin Pharmacol 2006;13:e50-62.
Vanoverbeke N, Annemans L, Ingham M, et al. A cost analysis of the management of attention-deficit/hyperactivity disorder (ADHD) in children in the UK. J Med Economics 2003;6:79-94.
Wolraich ML, Greenhill LL, Pelham W, et al. Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Pediatrics 2001;108:883-92.
Subject indexing assigned by NLM
Adolescent; Adult; Attention Deficit Disorder with Hyperactivity /drug therapy /epidemiology; Central Nervous System Stimulants /administration & Child; Clinical Trials as Topic; Cost-Benefit Analysis; Delayed-Action Preparations /economics; Female; Humans; Male; Markov Chains; Methylphenidate /administration & Netherlands /epidemiology; dosage /economics; dosage /economics
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Date abstract record published