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

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Economic model
TABLE 92 Alternative utility values used in sensitivity analysis of the economic model
Health state Utility value (SE)
Responder to ATX, no side-effects 0.959 (0.077)
Responder to IR-MPH, no side-effects 0.913 (0.128)
Responder to ER-MPH, no side-effects 0.930 (0.107)
Non-responder, no medication 0.880 (0.133)
SE, standard error.
Sensitivity to estimated utility values
The base case analysis employs estimates of the
utility associated with response to treatment and
non-response to treatment that are independent of
the treatment received. A responder to ATX
therefore receives the same utility value as a
responder to MPH or DEX. The submission by Eli
Lilly utilised a different set of utility estimates
derived using SG methodology. These estimates
valued response (and non-response) to treatment
dependent on the medication received. Hence
separate values were available for response (and
non-response) to ATX, IR-MPH and ER-MPH,
also separated by the presence or absence of
treatment side-effects. The review of the company
submissions highlighted some concerns about the
validity of these estimates, particularly the fact
that the utility of a non-responder without sideeffects
differs between treatments. For example,
the utility associated with non-response to ATX,
without side-effects, is estimated to be 0.902,
which compares with an estimated utility of 0.880
associated with non-response and no medication.
A difference in utility of 0.022 is relatively large in
this population, particularly between health states
with identical characteristics.
A sensitivity analysis was conducted using these
alternative estimates of utility. The reason for the
differences in utility of non-response by treatment
(including no treatment) is unclear, so the
sensitivity analysis uses the utility of non-response
associated with no medication. Our model does
not separate responders into those with sideeffects
and those without, so we conducted the
sensitivity analysis including the utility of response
without side-effects. Table 92 shows the utility
values used in this sensitivity analysis.
The health state descriptions used to obtain these
valuations are shown in Appendix 10. These
vignettes were designed to maximise the
differences between treatments. The results of this
sensitivity analysis rely on the validity of these
health state descriptions. No estimate was
available for DEX, so the utility associated with IR-
MPH was applied to patients responding to DEX,
in accordance with the assumption made in the
submission by Eli Lilly.
The results of the sensitivity analysis are shown in
Table 93. Strategy 13 remained the cheapest
strategy, but it no longer dominated the other
strategies. By calculating the ICERs, according to
the rules of dominance and extended dominance
(p. 95), we see that strategies 5, 10, 11 and 16 are
not ruled out by dominance or extended
dominance. Strategies 5, 10 and 11 all feature
ATX as first-line therapy. This is unsurprising
given that a response to ATX is associated with a
utility gain of 0.046 over a response to IR-MPH
(and DEX). Response to ATX is associated with a
utility gain of 0.079 compared with non-response
with no treatment, whereas response to IR-MPH
entails a gain of only 0.033 over non-response
with no treatment. For comparison, in the base
case analysis, response is associated with a utility
gain of 0.064 compared with non-response.
Figure 24 shows the cost-effectiveness acceptability
frontier for the optimal strategies in this sensitivity
analysis. If society were willing to pay £30,000 per
additional QALY, strategy 11 is the optimal
strategy with a 3% probability of being the optimal
strategy.
The discontinuities in the frontier in Figure 24
illustrate that the distribution of incremental net
benefit is skewed. Strategies 13 and 6 have a
higher probability of being cost-effective than
strategies 5, 10, 11 and 16 for values of willingness
to pay per QALY >£11,000, but they do not have
the highest expected net benefit.
Co-morbid conditions
The base case analysis does not include the
additional costs of the common co-morbid
conditions of CD and ODD. Estimates of the
additional cost of common co-morbid conditions
were available from the same source that provided