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

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Economic model
TABLE 94 Additional resource use data attributed to co-morbid conditions in patients with ADHD
Item Average per year Lower CI limit Upper CI limit
Consultations
Psychiatrist 2.25 1.30 3.00
Paediatrician 0.25 0.00 0.70
GP 2.25 1.30 3.40
Tests
Blood test 0.53 0.00 1.43
ECG 0.03 0.00 0.07
the non-drug costs used in the base case analysis.
Table 94 presents the additional cost of these comorbid
conditions.
When the model is re-analysed to include these
additional costs, strategy 13 remains the dominant
strategy, with a cost of £1491 and 0.8281 QALYs
per patient over a time horizon of 1 year. This
compares with a cost of £1098 and 0.8289 in the
base case (difference in QALYs due to random
variation). This sensitivity analysis relies on the
assumption that the relative treatment effects on
ADHD are independent of the presence of comorbid
conditions.
If DEX is not suitable as first-line therapy, strategy
7 (first-line IR-MPH, second-line DEX, third-line
ATX) is optimal. In this analysis strategy 9 (firstline
ER-MPH12, second-line DEX, third-line ATX)
is more costly and more effective compared with
strategy 7, but the cost per QALY gained is
£5,697,763.
The base case analysis also does not consider
patients with co-morbid conditions that make
them unsuitable for treatment with stimulants,
such as severe tics or Tourette’s syndrome. In these
patients, MPH and DEX may be unsuitable,
leaving ATX as the only available
pharmacotherapy. The submission by Eli Lilly
used data from an unpublished trial comparing
ATX with placebo in children with Tourette’s
syndrome and severe tics. The response rate to
ATX was found to be 66.67%, defined as a
reduction of ≥25% on the parent-rated ADHD-RS,
which compares with a response rate of 65.08% in
children and adolescents without these
contraindications to treatment with stimulants.
No published trials were available comparing ATX
with placebo in patients with severe tics or
Tourette’s syndrome. As such, a sensitivity analysis
was conducted based on the assumption that the
relative treatment effect of ATX on ADHD is
independent of the presence of tics or Tourette’s
syndrome. Using the base case estimates of
response rates (estimated from trials that excluded
patients with severe tics and Tourette’s syndrome),
the cost per QALY gained with ATX compared
with no treatment (strategy 19) is £7951. Hence
treatment with ATX appears cost-effective in
patients who are contraindicated to treatment with
stimulants. If society were willing to pay £30,000
per additional QALY, treatment with ATX would
have an 86% probability of being cost-effective.
Sensitivity to time horizon
The base case model considers a time horizon of
1 year. At the end of this year, the cohort is
divided into responders on various medications
and non-responders on no medication. It is
unlikely that the proportion of patients in each of
the health states at the end of 1 year will remain
the same indefinitely. Unfortunately, there is a lack
of long-term data in this area that might inform
the model in terms of long-term adverse events
with treatment, length of treatment and long-term
benefits of treatment. As such, no extrapolation
was considered in the base case analysis.
Two studies were identified that explored the agedependent
decline of symptoms of ADHD. 148,158
The data provided by Hill and Schoener 148 were
transformed into a yearly probability of remission
of 13% (50% over 5 years). This estimate of 50%
remission over 5 years was calculated using a nonlinear
regression analysis on cohorts of children
who received a mixture of treatments for ADHD.
The yearly rate was applied to patients in each
health state, including non-responders. Patients in
remission were assumed to be identical with
medication responders, without the cost of
medication itself. The long-term model has been
described in the section ‘Extrapolation’ (p. 103).
Figure 25 illustrates the simple structure, which
employs a 1-year cycle length. Table 95 shows the
results from the extrapolation. Strategy 13 remains