Donepezil, rivastigmine, galantamine and memantine for ...

effectiveness of rivastigmine, 90–93 together with the
industry submission and one published abstract. 94
Cost-effectiveness studies for rivastigmine and the
industry submission are based almost solely on
methods involving MMSE as a measure of
cognitive function, with rivastigmine treatment
related to delays in cognitive function and patient
benefits over time. The methodology used is based
on an assumption that these delays in cognitive
decline (as measured by MMSE) translate into
meaningful patient outcomes, and this review has
highlighted uncertainties over the validity of using
the MMSE alone to model disease progression.
The two UK studies 90,91 and the industry
submission report additional costs associated with
rivastigmine treatment (the relatively small cost
savings reported by Fenn and Gray 91 would be
offset once drug costs were included in the
analysis). The studies by Hauber and
colleagues 92,93 are for the USA and Canada and
do not report sufficient detail for us to be
confident on the cost calculations applied, the
USA study does not include drug costs and the
Canadian Study is from a societal perspective
including costs for informal caregiver time. The
industry submission reports a baseline cost per
QALY of £24,600; however, concerns over the
methods used have been highlighted and it may
be that this is an underestimate of the costeffectiveness
of rivastigmine treatment. Where
assumptions are made above related to cost inputs,
the cost per QALY remains below £29,000, but
with subsequent alteration to the inputs for health
state utility (QALYs) the cost per QALY rises to
£45,925.
Cost-effectiveness analysis by SHTAC, using the
cost-effectiveness model described above, suggests
that rivastigmine treatment has a cost per QALY
in excess of £57,000. Incremental QALY gains are
small over 5 years and additional costs to the NHS
and PSS, largely comprising the cost for
rivastigmine treatment, are in the region of
£2100–2300. The model suggests that rivastigmine
treatment reduces the time spent in FTC (delays
progression to FTC) by 1.43–1.63 months, but cost
savings associated with this reduction do not offset
the cost of treatment sufficiently to make it appear
a cost-effective intervention.
Cost-effectiveness of galantamine
Cost-effectiveness studies for galantamine are very
similar in methods, and reflect country-specific
analyses; all are sponsored by the manufacturer.
Clinical trials have shown statistically significant
differences in outcomes between galantamine and
placebo, but these outcomes need some
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Health Technology Assessment 2006; Vol. 10: No. 1
interpretation in the context of patient
experiences over the longer term, in terms of
disease progression and the need for FTC and
institutionalisation. The cost-effectiveness
literature has attempted to extrapolate to longterm
patient outcomes, using the need for FTC.
Published studies show various country-specific
analyses, consistently reporting that treatment with
galantamine results in a delay to requiring FTC
(approximately 2.5–3 months over a 10-year time
horizon), but the generalisability of costeffectiveness
studies to the UK is limited owing to
country-specific analyses (e.g. Getsios and
colleagues 95 use unit costs for hospitalisation that
are excessive compared with UK costs, and
Garfield and colleagues 96 include paid caregiver
time). The UK study by Ward and colleagues 99
reports a cost per QALY of £8693 for 16-mg
galantamine treatment and £10,051 for 24-mg
galantamine (the industry submission uses costeffectiveness
estimates from Ward and colleagues),
but concerns over the methods employed have
been highlighted above, and suggest that this is an
underestimate of the cost-effectiveness of
treatment. SHTAC present results from the
industry model using alternative parameter and
time-frame inputs, and report a cost per QALY of
over £49,000.
CEA by SHTAC, using the cost-effectiveness
model described above, suggests that galantamine
treatment has a cost per QALY in excess of
£68,000 per QALY. Incremental QALY gains are
small over 5 years and additional costs to the NHS
and PSS, largely comprising the cost for
galantamine treatment, are in the region of
£2650–2850. The model suggests that galantamine
treatment reduces the time spent in FTC (delays
progression to FTC) by 1.54–1.73 months, but cost
savings associated with this reduction do not offset
the cost of treatment sufficiently to make it appear
a cost-effective intervention.
SHTAC cost-effectiveness analysis
for memantine for moderately
severe to severe AD
Published studies and the industry submission use
the same modelling methods when estimating the
cost-effectiveness of memantine, modelling disease
progression over time using transition
probabilities for health states described using
severity, dependency and location.
This model has not been replicated; an outline
description and review of the model is provided,
135