Donepezil, rivastigmine, galantamine and memantine for ...

epresentation of disease progression (i.e. three
states for pre-FTC, FTC or death), the
epidemiological dataset upon which it is based
(i.e. potential limitations in the data from the
small number of observations at patient level and
the small numbers associated with later time
periods) and the statistical uncertainties inherent
in the two-stage predictive risk equations that
characterise the model. Mendiondo and
colleagues 181 highlight concerns over the AHEAD
modelling methodology, but also conclude that it
may be useful in comparing costs or changes in
AD progression due to different therapies.
SHTAC cost-effectiveness analysis
for mild to moderately severe AD
Cost-effectiveness of donepezil,
rivastigmine and galantamine
The literature on the cost-effectiveness of
donepezil is based on the use of health states
defined according to MMSE scores and transition
probabilities between these states. The literature on
the cost-effectiveness of rivastigmine is based on a
hazard model predicting disease progression over
time. The industry submissions to NICE for
donepezil and rivastigmine use MMSE alone to
define stages of disease severity, with transition
probabilities and observational data respectively
used to model disease progression over time on the
basis of MMSE scores. All published costeffectiveness
studies for galantamine use the
AHEAD model to model disease progression over
time; this uses the need for FTC as an endpoint,
and applies a statistical technique (predictive risk
equation) to estimate the benefits from
galantamine treatment. Some reservations over the
use of this methodology have already been
highlighted. The industry submission for
galantamine also uses the AHEAD model, referring
directly to the published literature, and specifically
the study by Ward and colleagues99 for estimates of
the cost-effectiveness of galantamine in the UK.
Rather than replicate the modelling approaches
presented in the industry submissions, which may
be suboptimal, the present authors (1) provide an
outline summary and review of the models
submitted and (2) provide (below) some alternative
cost-effectiveness results from the industry model
based on alternative parameter inputs.
In addition to the review of industry models and
the presentation of some alternative costeffectiveness
results from industry models, a simple
disease progression model for mild to moderately
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Health Technology Assessment 2006; Vol. 10: No. 1
severe AD to consider the cost-effectiveness of
donepezil, rivastigmine and galantamine has been
developed. This model, described below, is
illustrative and has been developed to help
consider the cost-effectiveness of these three
alternative products when modelling of costeffectiveness
estimates is undertaken using similar
methods (i.e. same model method applying
product-specific effectiveness data on differences
in ADAS-cog scores).
SHTAC model to estimate the
cost-effectiveness of donepezil,
rivastigmine and galantamine
Statement of problem and perspective of
cost-effectiveness analysis
As stated previously, it is felt by the present
authors that all currently available modelling
methods in AD are suboptimal in their approach
to modelling disease progression, therefore the
model here is presented as ‘illustrative’ of the costeffectiveness
profile for donepezil, rivastigmine
and galantamine. The model estimates the costeffectiveness
of pharmaceuticals plus usual care
versus usual care alone in a UK context. The
perspective of the cost-effectiveness analysis is that
of a third-party payer, namely the NHS and PSS in
England and Wales. Costs associated with patient
care from the NHS and PSS are included in the
analysis, together with all patient benefits.
Strategies/comparators
Descriptions of the use of pharmaceuticals in AD
and the relevance of using usual care as the
comparator strategy can be found in Chapter 2.
Model type and rationale for structure
A Markov-type disease progression model has been
developed for mild to moderately severe AD, to
consider the cost-effectiveness of pharmaceuticals
for AD. The model considers the experiences of a
cohort of AD patients (mild to moderately severe)
over a 5-year period for the strategies of usual
care alone and usual care plus pharmaceutical
intervention, and compares the differences in costs
and outcomes associated with the different
management strategies.
The cost-effectiveness models used in the
literature and the industry submissions exhibit a
large degree of variation, both across and within
products, in terms of the methods used to model
disease progression and the endpoints used to
consider patient benefits. The present model has
been developed to offer an opportunity to
consider the three products when a similar
modelling method has been employed.
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