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

Extrapolation
A secondary analysis extends the time horizon
from 1 year to when the cohort reaches 18 years of
age. In this secondary analysis, it is assumed that
patients on active medication are given an annual
drug-free period of 2 weeks to assess the ongoing
need for medication. A proportion of patients,
whose symptoms are found to be in remission, do
not resume medication following this 2-week drugfree
period. The model also incorporates the
proportion of patients on no treatment who
experience remission from symptoms, and hence
are no longer defined as non-responders. The
model makes the simple assumption that patients
not in remission will return to their pre-drug-free
period medication, that this medication will be
tolerated and that the patient will continue to
respond on medication as before. Patients in
remission are assumed to be identical to
responders in terms of utility and non-drug health
expenditure.
In this extended analysis, costs are discounted at
an annual rate of 6%, and health benefits are
discounted at an annual rate of 1.5%, in
accordance with NICE guidance.
Clinical effectiveness
As identified in the clinical effectiveness review in
Chapter 4, there is huge variation in the
instruments used and the outcomes reported
regarding the clinical effectiveness of alternative
treatment options. This reflects the lack of
consensus on what constitutes successful treatment
of ADHD in the absence of a biological marker
and hampers between-study comparisons. The
clinical effectiveness review addressed this issue of
disparity by identifying the most valid and reliable
measure in consultation with a clinical expert and
adopting a standard method of presentation. Thus
Chapter 4 presents an overview of the change in
mean score on the Conners’ Teachers
Hyperactivity Subscale (CTRS-H) and Conners’
Parent Hyperactivity Subscale (CPRS-H). Although
this measure facilitates comparison across a large
number of studies, there are limitations in its use
in a decision-analytic model. As noted in the
literature review in Chapter 4, if this measure is
used, a gain of one point on the scale is valued the
same, regardless of where one begins on that scale,
so the relative value of different effect sizes is not
readily interpretable. In addition, no published
studies were available to provide a link between
mean CTRS-H or CPRS-H score and utility data.
In order to identify the most optimal treatment
strategy in a decision-analytic model, one must be
able to value the differences in outcome, and this
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Health Technology Assessment 2006; Vol. 10: No. 23
is not currently possible with mean CTRS-H or
CPRS-H score.
Alongside mean scores on various rating scales, a
proportion of studies also report response rates to
treatment. These indicate the percentage of
children who reach a specified level of
improvement. Response rates would be preferred
from an economic evaluation perspective for two
reasons. First, they explicitly identify a clinically
meaningful change on the rating scale used to
determine effectiveness. Second, the utility data
currently available for patients with ADHD pertain
to the states of ‘responder’ and ‘non-responder’.
Therefore, an economic model based on response
can estimate a cost per QALY, which is more
interpretable and generalisable than a cost per
point gain in CTRS-H or CPRS-H. On the other
hand, there are limitations with the use of
response rate as a measure of clinical effectiveness,
primarily owing to the lack of an agreed definition
of response to treatment for ADHD. This makes
comparisons between studies difficult as they may
use different definitions.
Hence the measure of clinical effectiveness in the
economic model is response rate to treatment.
This reflects the approach used in the existing
economic literature and the manufacturers’
submissions, but must be interpreted according to
the caveats used in calculating response rates. The
model considers a number of different sets of
response rates, each estimated from the clinical
studies with different inclusion criteria. The first
set of response rates was estimated using the most
common definition of response in the included
studies, namely a score of 1 or 2 (much improved
or improved) on the clinician-rated Clinical Global
Impression improvement subscale (CGI-I). These
rates are used in the base case analysis. This allows
a comparison of all relevant treatment strategies
without making assumptions about the
comparability of different definitions of response.
The second definition of response is a score of 1
or 2 on the clinician-rated Clinical Global
Impression severity subscale (CGI-S). There was
no estimate available for the response rate to DEX
using this definition. A third group of trials
defined response as a reduction of ≥ 25% on the
parent-rated ADHD-RS. Measures of response
according to this criterion were only available for
placebo, ATX and ER-MPH12. Hence for this
third definition of response, further modelling was
required in order to compare all relevant
treatment strategies [details follow in the section
‘Sensitivity to structural assumption regarding
MPH’ (p. 117)]. Finally, estimates of response
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