Donepezil, rivastigmine, galantamine and memantine for ...

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Economic analysis
independent, (b) initially moderately severe and
dependent, (c) initially severe and independent and
(d) initially severe and dependent. In the first three
of these subgroups improvements in clinical effect
and cost savings were greater than the base-case
analysis. In group (d), memantine was associated
with an improvement of 0.02 year (7 days) in time
spent in an independent state, a delay of 0.04 year
(14 days) before institutionalisation, an increase of
0.01 QALY and an incremental cost of £42 over
2 years.
Sensitivity analysis is reported in relation to
duration of treatment and efficacy. The worst case
scenario is presented as an improvement of
0.07 year in time spent in an independent state,
0.04 year in the community, and additional 0.03
QALYs and cost savings of –£529.
Industry submission on costeffectiveness
of memantine
In their submission to the NICE technology
appraisal process, the manufacturer of memantine
(H. Lundbeck) presents CEA for memantine
compared with usual care (no AD pharmacological
treatment), and cost-effectiveness of memantine
when added to the management of patients
stabilised on donepezil, compared with the use of
donepezil alone, in moderately severe to severe
AD patients. Their submission contains CEA on
memantine versus no pharmacological therapy
based on the study by Jones and colleagues, 104
which is discussed above (although further detail is
provided on methods and findings). Furthermore,
the manufacturer’s submission presents separate
CEA on the comparison of memantine in
combination with donepezil versus donepezil alone.
Presentation of the cost-effectiveness of
memantine versus no pharmacological therapy
largely follows the data presented above from the
study by Jones and colleagues, although there are
some small differences present in the
manufacturer’s submission. The submission
reports results at base-case scenario as an
incremental QALY gain of 0.04 and a mean cost
reduction per patient of £1960, suggesting
memantine as a cost-effective and cost-saving
treatment. Cost savings were reported across a
range of cost categories with most areas reported
as having small differences (in absolute terms), yet
hospitalisation and institutionalisation costs were
reduced by £2530 and £1149, respectively (shifts
of –7.2 and –4.5%).
Subgroup analysis for memantine versus no
pharmacological therapy reported memantine as
cost saving in all patient groups except those who
were severe and dependent AD patients, where the
mean cost per QALY was £4200 (0.01 QALY, and
an additional £42). One-way sensitivity analysis on
key parameters showed the effect of memantine
on costs and QALYs decreased with decreasing
effects on dependency, but remained in favour of
memantine (additional benefits, cost savings).
Memantine in combination with donepezil, versus
donepezil alone
Cost-effectiveness of memantine in combination
with donepezil was estimated by the manufacturer
using clinical data from the US study MEM-MD-
02. 74
[Commercial/academic confidential information
removed]
Comments on industry submission for
memantine
The industry submission is based on a state
transition model, describing disease states by
severity, dependency and location, and this is a
reasonable attempt to describe disease progression
in the more severely affected AD patient group,
where severity alone is not sufficient to
differentiate between patient groups. The time
horizon of 2 years seems appropriate, with
6-monthly cycles used to fit clinical data (see
Appendix 15 for an outline review of the model).
However, transition probabilities used to model
disease progression are from a combination of
observational data and clinical trial data, with
concerns over both in the context of the current
UK analysis. Baseline and memantine transit
probabilities for severity are from the clinical trial
by Reisberg and colleagues, 72 a 6-month RCT
(n = 252) (see Chapter 4). This trial reports a
statistically significant difference of 2.1 points on
the ADCS/ADL (functional outcomes), a nonstatistically
significant difference on CIBIC-plus, a
statistically significant difference on scores for the
SIB, no statistically significant difference on
MMSE, behaviour and mood (NPI) or the GDS,
yet transit probabilities show substantive
differences between memantine and placebo. For
example, with usual care (placebo) there is a
45.2% probability of transiting from moderately
severe to severe over a 6-month cycle, whereas
with memantine this probability is stated to be
22% (a difference of 23%). The power of the
clinical trial to drive such differences in the
disease progression model must be questioned.
Transit probabilities by dependency are cited from
the LASER-AD Study 146 and the RCT from