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

of the 64 identified in the clinical effectiveness
review. This analysis showed that a treatment
strategy of first-line DEX, followed by second-line
IR-MPH for treatment failures, followed by thirdline
ATX for repeat treatment failures was
optimal. This strategy remained optimal when
including the additional costs of co-morbid
conditions, extrapolating the model to age
18 years, and using alternative estimates of
resource use in ADHD. A sensitivity analysis
employing alternative estimates of the utility
values associated with ADHD did alter the results,
but problems in interpreting these alternative
utility values mean that the result may not be
valid. It is interesting that, despite using a
different measure of efficacy to that used in the
clinical effectiveness review in Chapter 4, the
conclusions are broadly similar. Chapters 4 and 6
indicate the superiority of drugs over no drug
therapy, but show no significant difference in
terms of efficacy or side-effects between the active
therapies. This lack of significant difference could
be due simply to the lack of available evidence in
both cases. The main additional feature of this
chapter in comparison with Chapter 4 is the
consideration of costs. Given the lack of evidence
for differences in efficacy between active therapies,
the results of the economic model are largely
driven by drug cost, in which there are marked
differences between the relevant comparators.
It is possible that DEX may not be considered
suitable as a first-line therapy; if the interpretation
of its licence is that it can only be used following
failure on another medication for ADHD, or if
concerns about its abuse potential (not reflected in
the model) are so much greater than concerns
about MPH. In this case, the model identified an
optimal treatment strategy of first-line IR-MPH,
followed by second-line DEX for treatment
failures, followed by third-line ATX for repeat
treatment failures. However, data on the relative
abuse potential of MPH and DEX are scarce, and
the costs and dis-benefits associated with such
abuse would be hard to quantify in this simple
model. As such, we presented results for the case
where DEX is considered suitable as first-line
therapy, and the case where it is not, leaving the
reader to decide whether strategies with DEX firstline
therapy are relevant comparators.
It is feasible that factors in the school environment
or characteristics of particular patients with
respect to compliance make a midday dose of
medication unworkable. If this is the case, the
analysis in the section ‘Sensitivity to structural
assumption regarding MPH’ (p. 117) indicates
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Health Technology Assessment 2006; Vol. 10: No. 23
that ER-MPH12 would be preferred to ATX,
and so would precede ATX in any treatment
strategy.
In order to increase the number of trials used in
calculating response rate, the MTC model used to
synthesise the data in the base case analysis was
extended to estimate a relationship between
responses defined by different criteria. Bringing in
additional trials increased the certainty around the
model results, and a three-treatment strategy
(first-line DEX, second-line IR-MPH, third-line
ATX) remained cost-effective. However, even this
extended analysis only employs data from 14 out
of 64 trials. The model also relies on non-drug
resource use data estimated using an expert panel.
This increases the uncertainty in the model
results, but the model was robust to using very
different estimated resource use.
For a decision taken now, with current available
data, the results of the economic evaluation clearly
identify an optimal treatment strategy. However,
the model is not without limitations, and new data
on long-term outcomes associated with medical
management of ADHD could change the analysis
significantly. The model considers a broadly
defined set of patients with ADHD, as the data did
not allow us to discriminate between patients in
terms of ADHD subtype, gender, age or previous
treatment. The resource use data are based on
expert opinion, which may not reflect resource use
in practice in the UK. Similarly, resource use and
monitoring in UK practice may be lower than that
observed in clinical trials, which could translate to
lower effectiveness in practice compared with that
observed in clinical trials. The effectiveness data
used in the model are based on trials set in North
America, owing to the lack of data specific to the
UK. Although there are many trials in this area,
the outcome measures used, and the way in which
results are reported, vary widely. As such, the
treatment effects used to populate the economic
model are based on a subset of the clinical
evidence, predominantly recent trials. An analysis
of treatment effects that included all the available
trial data would involve many assumptions
regarding the clinical value of mean difference in
different rating scales, the role of baseline mean
score in relation to mean difference, the
distribution of mean score and mean difference on
each rating scale and the utility associated with
mean score on different rating scales. Such
assumptions would go beyond what is justified by
the data, so it was felt that a more robust synthesis,
based on a subset of the available evidence, would
be more appropriate.
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