Donepezil, rivastigmine, galantamine and memantine for ...

general clinical trial literature (e.g. effect of
treatment on psychotic symptoms).
As the drug treatments are portrayed as having
benefits in terms of delaying disease progression
(to severe AD or to FTC), the cost structure in the
CEA is very important, and central in driving the
findings, that is, if severe AD (or FTC) is described
as being very resource intensive and expensive,
then the drug treatment will be seen as more
attractive if it is assumed it will offer cost savings
by reducing the time a patient spends in such a
disease/health state. Most if not all studies raise
some concerns over the way they structure the cost
of care for AD. Our estimates presented above
relate to costs of care for AD in the context of
health states describing pre-FTC and FTC (in
SHTAC analysis), and find that many studies use
costs in excess of those suggested in our review. It
has been highlighted that not all long-term
institutional costs will fall on the NHS and PSS
budget, and many patients with AD will either be
self-funding in institutional care or part-funded,
and some allowance for this made in the cost
estimates used. None of the cost studies or costeffectiveness
studies identified have discussed this
issue or made allowance in analysis. From our
sensitivity analysis this issue has a big impact on
cost-effectiveness findings.
Some alternative cost assumptions in the industry
models for donepezil, rivastigmine, and
galantamine are highlighted and the resultant
cost-effectiveness estimates from the models
presented. Where only cost input alterations to the
donepezil model have been made it suggests
findings indicative of a cost-per QALY of £50,000
(deterministic analysis, and we suggest
probabilistic analysis will give a higher cost per
QALY). It is felt by the present authors that this
adds some support to the findings in the SHTAC
model, given that the industry submission makes a
number of other optimistic inputs related to
treatment effectiveness.
For rivastigmine it was not felt that the cost
structure of the industry model is far from our
view, although estimates related to monitoring are
some way apart (industry cost for monitoring does
not favour rivastigmine, as it is much higher than
the SHTAC estimate). Where amendments are
made to the assumption on utility weightings in
the model a resultant cost per QALY in the region
of £50,000 (using deterministic analysis) is seen,
and the findings offer some support for the
estimates presented by SHTAC against the costeffectiveness
of rivastigmine, given the use in the
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Health Technology Assessment 2006; Vol. 10: No. 1
rivastigmine model of effectiveness data from a
longer term open-label study that shows findings
potentially subject to serious bias.
Where SHTAC have made adjustments to the
industry model for galantamine the cost per
QALY findings (over 5 years) are not drastically
different from those in the SHTAC model, with
the observed difference potentially attributable to
the differences in the modelling of mortality, the
use of an additional monitoring cost and the use
of an additional effectiveness impact in the
industry analyses (i.e. difference in presence of
psychotic symptoms). Furthermore, there are
structural differences in the SHTAC model
compared to the industry model.
Overall, it is noted that given the relatively small
incremental health gains, e.g. QALY gains,
presented in the cost-effectiveness analysis for
these treatments, the subsequent cost-effectiveness
summary statistics (e.g. cost per QALY) are very
sensitive to relatively small changes to the
estimated incremental costs; e.g. where
incremental QALY gains are 0.04, it takes an
incremental cost of only £2000 (which may not be
regarded as substantive or prohibitive in some
cases over a 5-year period) to produce a cost per
QALY of £50,000.
Summary: cost-effectiveness analysis for
mild to moderately severe AD
The clinical effectiveness review (Chapter 4)
reported findings from RCTs, indicating that drug
treatments (donepezil, rivastigmine and
galantamine) show statistically significant benefits
across various outcome measures (e.g. cognitive
outcomes, global health outcomes) in the
treatment of mild to moderately severely AD.
However, the link from clinical trial outcomes to
longer term patient-related outcomes (e.g. delay
in disease progression, reduction in
institutionalisation) is largely absent in the current
literature, with modelling studies used to predict
disease progression over time. The difficulties
present in estimating cost-effectiveness for these
treatments in AD is discussed above, in some
detail; however, accepting these difficulties, the
findings from the cost-effectiveness review and
analysis for donepezil, rivastigmine and
galantamine in mild to moderately severe AD are
summarised below.
Generally, published cost-effectiveness studies and
the industry submission are varied in their
methods, and offer an unclear picture owing to
differences in methodological approaches,
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