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
constellation of problems rather than a single
disorder, with core symptoms of inattention,
hyperactivity and impulsivity and other more
general symptoms such as poor school
performance and poor social functioning. 121 Since
these behavioural traits can be present in
unaffected children, symptoms and functionalitybased
outcomes need to have discriminant validity,
that is, they should be able to discriminate
between children with and without ADHD. It has
been suggested that there might be unique
patterns of effects created by different treatments
(e.g. drug interventions versus BT) and a single
outcome measure might not be sufficiently
sensitive. 118 Although measures that are used for
reporting outcomes in a disaggregated way may be
useful from a clinical perspective, the use of these
instruments has limitations from a decisionmaking
perspective. Many of the measures feature
subscales, and the scoring of the instrument may
not be designed to provide an overall summary
score. Unless the relative importance of each
subscale or of each different profile measure can
be valued, it is not possible to use these measures
to calculate the net impact on HRQoL.
When assessing the cost-effectiveness of an
intervention, the use of such disparate measures
may lead to conflicting results depending on the
instrument or subscale used. One way to overcome
this problem is to use a preference-based index of
HRQoL. These provide a summary score, typically
between 0 (death) and 1 (full health), with the
relative importance of changes in different
dimensions of health being weighted according to
people’s preferences. Given the perspective of
NICE, the most relevant values are those of the
general population of England and Wales. The
focus of this review is children and adolescents so,
in principle, their preferences may be most
relevant. When preference values are obtained
using the standard gamble (SG) or time-trade-off
(TTO) techniques, they can be used to represent
utilities. (The NICE technical guidance requires
that health states should be measured in patients
using a generic and validated classification system
for which reliable UK population preference
values, elicited using such a choice-based method,
for example. 122 ) Utility values for health states can
be combined with the length of time spent in
those health states to calculate quality-adjusted
survival.
The quality-adjusted life-year (QALY) is commonly
used to measure health outcomes in health
economic evaluations, combining QoL with quality
of life in a single measure. Two studies contained
utility information for use in the construction of
QALYs 123 (Gilmore and Milne 123 is based on the
Wessex Institute DEC Report number 78 124 ), 125
(authors include Eli Lilly employees, producers of
Strattera/ATX).
Gilmore and Milne 123 generated QALYs based on
data from the IHRQoL. 119 The population
preference-based IHRQoL system was used, which
incorporates three dimensions: disability,
(physical) discomfort and (emotional) distress.
Since the authors could not find accurate
estimates of disability directly in the literature,
they used their own judgement, in consideration
of trial evidence. It was assumed that the QoL
improvements were 0.086 per individual for a
year. [The IHQoL health state was assumed to
change from that of no pain, slight social disability
(some role functions slightly impaired by social
disability) and moderate emotional distress
(anxious and depressed most of the time but
happy and relaxed some of the time) to no pain,
no physical or social disability and slight
emotional distress (happy and relaxed more of the
time, but anxious and depressed some of the
time). Based on IHQoL data, this generates a
score of 0.970 – 0.884 = 0.086]. Estimations were
made for 1 year only, reflecting the better quality
of shorter-term trial data.
Initially, to calculate QALYs it was assumed, based
on the literature, that benefits observed at
4–6 months persisted for the year of follow-up
provided that medication continued. In addition,
it was assumed that 6% of individuals discontinued
treatment over the year owing to side-effects and
that the average response rate in those who
remained within the trial was 70%. From this, it
was estimated that 100 children gained 94.06
QALYs per year using MPH compared with 88.4
QALYs per year for the placebo arm, an
incremental difference of 5.66 QALYs or 0.0566
QALYs per child.
There are a number of caveats surrounding the
usefulness of these findings. The authors
acknowledge that the main limitation of their
work lies in the generation of the QALY using the
IHRQoL. Values for health states for children with
ADHD were obtained using expert judgement with
consideration of published trials. The process of
synthesising this information from the literature
was not explained. The authors state that the
IHRQoL is not a sensitive tool for measuring the
types of disabilities encountered in ADHD. They
mention that typically children with ADHD have
moderate to severe social disability, whereas the