A systematic review and economic model of the effectiveness and ...

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Review of economic evaluations of ADHD drug interventions in children and adolescents
associated with multiple daily dosing is expected to
result in higher total costs. The impact of comorbid
conditions on the costs of care was not
assessed, nor were patient preferences or QoL
variables. The model relies on assumptions about
the relative efficacy of the drugs evaluated and
does not have a strong evidence base. Metadate
CD was assumed to have a higher response rate
than its generic counterpart, ER-MPH8, and the
authors failed to justify this.
Vanoverbeke and colleagues 129 also used a decisionanalytic
framework to model costs for management
of ADHD in 6–16-year-old children in the UK.
Medications compared starting treatment with IR-
MPH (once, twice or three times daily), Concerta
XL or BT over a 1-year time horizon.
An incidence-based decision tree was constructed
and the probabilities of success or failure were
based on average probabilities derived from the
literature. The probabilities for second-line
treatment were obtained from an expert panel of
eight UK psychiatrists and paediatricians, as were
data on treatment choices in response to adverse
events, co-morbidities and/or insufficient response
to treatment. Six out of the eight experts involved
also estimated resource use data for a typical
ADHD patient requiring treatment. To obtain the
data from an expert panel a two-stage approach
was followed, including a questionnaire completed
independently. Group average responses and
range of responses for each item were presented
and the experts were asked to provide new
estimates and a ‘certainty score’ to indicate the
expected variability associated with a given value
(of between one and four).
Costs were based on published estimates and
hospital prices and relate to 2001. Costs of
medications, laboratory tests, clinical personnel
and school staff personnel involved in BT were
included. Clinical outcomes for BT and IR-MPH
were obtained from the MTA trial and for Concerta
XL were obtained from Pelham and colleagues. 82
The cost of starting treatment with IR-MPH was
marginally lower than with Concerta XL (£1332
and £1362, respectively) and BT was the most
costly initial treatment (£2147). The probability of
treatment success was highest for Concerta XL
(77.8%), 82 then IR-MPH (55.6%), 133 followed by
BT (33.8%). 133
Data from different trials were used in the model
and this breaks the randomisation achieved in the
individual trials. As the authors state, Pelham and
colleagues’ study 82 on which the Concerta XL
clinical outcomes are based was a short-term, smallscale
study. A probabilistic sensitivity analysis was
undertaken which showed that results were sensitive
to treatment success and the proportion of patients
with co-morbidities. Although the sensitivity
analysis did not alter the results, the response rates
used in the model may be questioned.
In summary, across the five studies reviewed
above, all were based on a 1-year time horizon,
with the exception of the Lord and Paisley study 4
that covered a period of 14 months. However,
ADHD and treatment are known to continue for
much longer. Therefore, no consideration of longterm
adverse events or outcomes is incorporated
within the analyses. None of the full economic
evaluations compared all treatment strategies
relevant to this review. Zupancic and colleagues 126
did compare a number of treatments, but no
assessment of ATX drug therapy, which is
necessary for this review, was provided. A common
feature across all studies is the lack of data, with
expert/author opinion being used to fill in gaps.
In addition to the existing economic evaluations,
three submissions were received from Janssen-
Cilag, Celltech and Eli Lilly.
Review of the Janssen-Cilag
submission
Overview
The aim of the Janssen-Cilag submission was to
compare Concerta XL (ER-MPH12) with IR-MPH,
ATX, Equasym XL (ER-MPH8) and behavioural
therapy (BT) using new evidence made available
since the previous NICE guidance was issued. 134
The previous guidance recommended the use of
IR-MPH as part of a comprehensive treatment
programme, including advice and support to
parents and/or teachers and potentially BT, for
children diagnosed with severe ADHD. ‘Severe
ADHD’ was defined as broadly similar to HKD,
although it also includes some patients with severe
problems with inattention and/or hyperactivity
who do not meet the diagnostic criteria for HKD.
Treatment initiation was restricted to child and
adolescent psychiatrists or paediatricians, but
prescriptions could then be maintained by GPs.
A cost–utility analysis (classified CIC) was
conducted based on the results of two recent
randomised, open-label studies comparing
Concerta XL with IR-MPH 90 and ATX 99 and the
MTA trial. 133 The model took the form of a