Donepezil, rivastigmine, galantamine and memantine for ...

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Economic analysis
4. The model estimates of cost-effectiveness are
driven by relatively high estimates for
utility/QALY gains (compared with published
literature and other industry submissions), an
incremental gain of 0.0862, but it is difficult to
adjust this in a simple SHTAC analysis as it is
generated from an equation (predicting a
1-point change in MMSE results in a difference
of 0.03 QALY). SHTAC have crudely altered
this equation so that the active coefficient of
0.029793 is divided by two, i.e. a 1-point
change in MMSE reflects a utility change of
0.015; this results in a prediction of a lower
level of utility per change in MMSE, and results
in an incremental QALY gain (base case) of
0.0431, essentially halving the benefits seen in
the base case industry analysis. This SHTAC
alteration is experimental and illustrative only,
and has no statistical grounding. However,
given that the utility gains in the model are
based on differences in MMSE between
treatment groups, as shown in Table 51
[commercial/academic confidential
information removed], we note that at 2 years
(already 47% dropout in rivastigmine trial) the
difference in MMSE is 1.4 points, reflecting a
utility difference of 0.041 on the QALY 0–1
scale. (For justification of the cost assumptions
for SHTAC parameters, see the text
accompanying the SHTAC model on
pp. 123–4.)
Galantamine – SHTAC adjustments to industry
model
Where SHTAC have used the industry model
with alternative assumptions for cost inputs and
time frame, it results in a cost per QALY of
£49,000, for the galantamine 24-mg dose (all
other functions in the model remain the same as
in the manufacturer’s analysis and no re-wiring
of the model has been undertaken). With
additional assumptions to reflect a higher
mortality rate, we may expect a higher cost per
QALY estimate.
Adjustments made by SHTAC to industry base
case model inputs:
1. Time frame set at 5 years (base case at
[commercial/academic confidential
information removed].
2. Cost per month for pre-FTC set to £328 (base
case at [commercial/academic confidential
information removed]).
3. Cost per month for FTC community remains
the same at [commercial/academic
confidential information removed].
4. Cost per month for FTC institution set at £937
(base case at [commercial/academic
confidential information removed]).
5. Drug cost increased by £0.60 per day (base case
at [commercial/academic confidential
information removed]) to allow for an additional
monitoring cost of £219 per year (i.e. two
additional outpatient visits, expected to cost
£216 per year). (For justification of these
alternative SHTAC parameters see the text
accompanying the SHTAC model on
pp. 123–4.)
Where only time frame is altered to 5 years from
the industry base case of [commercial/academic
confidential information removed], all other
settings as industry base case, the cost per QALY is
£17,385.
Comparison of SHTAC model and
analysis with industry cost-effectiveness
analysis
Concerns that the methods currently available to
model disease progression in AD are suboptimal
have been highlighted above, and a critical review
of the industry models has been provided.
Nevertheless, a model, similar to that used in the
industry submission for galantamine, has been
developed to consider the cost-effectiveness of
donepezil, rivastigmine and galantamine in the
treatment of mild to moderately severe AD,
comparing these treatments against usual care.
The model allows consideration of the three drugs
when similar methodology and cost inputs have
been used. The results are generally similar across
the three drugs (i.e. high cost-effectiveness
estimates), with differences by drug treatment
driven by the differences in the reported ADAScog
effectiveness measure used from the clinical
review presented in Chapter 4, together with
differences in product price.
The cost-effectiveness findings in the current
review are markedly different to the published
literature and also different to those findings
presented to NICE within industry submissions.
The published literature is almost entirely
comprised of industry-funded studies, and many
of the studies are presented from a societal
perspective, including patient and caregiver costs
outside of the NICE perspective (i.e. NHS and
PSS). The literature and the industry submissions
are largely driven by optimistic differences in
effectiveness of treatment, compared with usual
care, using either unpublished transition
probabilities from clinical trials or effectiveness
findings that are uncertain in the context of the