Donepezil, rivastigmine, galantamine and memantine for ...

104
Economic analysis
of this study]. Transit probabilities covering
severity, dependency and institutionalisation for
the no treatment cohort were based on clinical
trial data from Reisberg and colleagues (2003) 72
and data from the LASER-AD Study. Transit
probabilities for dependency and location were
based on a transformation of the rates from the no
pharmacological treatment group using an
estimated OR for memantine versus placebo,
using clinical trial data. Treatment effect was
applied to the first 12 months (2 × 6-month
cycles), using data from the RCT by Reisberg and
colleagues 72 (6 months) and an open-label
follow-up study (6 months post-trial) (Reisberg B
and colleagues, 2000, unpublished). Dropouts
from treatment were not considered within the
model.
The model uses a multiplicative probability to
transit patients between states defined according
to a combination of disease severity, dependency
and location. Where patients are defined as
institutionalised (either at the start of the model
or on entering an institutionalised health state)
they remain in that state, with transit probabilities
applied to patients in a community setting only
(either remain in community or enter institution).
The model uses Monte Carlo simulation methods
in a probabilistic sensitivity analysis, (although
Jones and colleagues do not present CEACs,
presenting only range and best- and worst-case
scenarios). Dirichlet a priori distributions were
used to handle uncertainty associated with
transition probabilities in the model.
Estimates of outcomes
François and colleagues report that patients
treated with memantine showed greater duration
of independence (a mean additional 4 months of
independence) and time spent in the community
prior to institutionalisation (approximately 1 extra
month), compared with placebo patients.
Outcomes are discounted at 5%.
Jones and colleagues report that based on model
findings, treatment with memantine compared
with no pharmacological treatment was expected
to result (over 2 years) in an improvement in
terms of years of independence (0.10 years, SD
0.04), an improvement in years in the community
(3 additional weeks before institutionalisation,
0.06 years, SD 0.04) and 0.04 (SD 0.03) additional
QALY. Outcomes are discounted at 3.5%. Health
state utility values used are 0.65 (SD 0.20) for
independent AD health states and 0.32 (SD 0.31)
for dependent health states. These values are cited
from an unpublished Danish study by Kronborg
Andersen and colleagues, and the respective
sample sizes for these estimates were 131
independent patients and seven dependent
patients (although the authors do offer support
for the dependent values from a further small
sample of 18 dependent dementia patients). The
data used to derive health state values are from a
cross-sectional study reporting data from a Danish
cohort of patients aged 65–84 living in Odense,
Denmark. 145 In this study a total of 244 patients
with mild to severe dementia were interviewed.
Data have subsequently been mapped (by
Kronborg Andersen and colleagues) across to EQ-
5D health states, and values derived using Danish
EQ-5D population values (tariffs). The study
included 164 patients with AD, 132 of whom were
living in the community, and the mean MMSE
score for these AD patients was 20.6, hence the
generalisability of data from these patients to the
more severe patient group eligible for memantine
treatment may be in question (this issue is
discussed further below).
Subgroup analysis was undertaken by Jones and
colleagues, where treatment groups at the start of
the model were assumed to be only those classed
as (a) moderately severe and independent, (b)
moderately severe and dependent, (c) severe and
independent and (d) severe and dependent.
Outcomes for subgroups (a)–(c) were greater than
in the base case, ranging from 0.17 to 0.26
additional years in an independent state, 0.06 to
0.13 additional years in the community, and
between 0.07 and 0.09 QALYs. However, for
patients classed as severe and dependent (d), the
benefits were minimal (see Appendix 14).
Launois and colleagues (published as an abstract
and poster) 101 report analyses over a 5-year
period using a model similar to that described
above. They compare memantine 20 mg with
no pharmacotherapy and with a strategy where
patients are treated with donepezil when
moderately severe, followed by no
pharmacotherapy once patients reach a severe
state of AD. Transit probabilities for the treatment
arm containing donepezil were from a published
study (by Stewart and colleagues, 82 discussed in
the section ‘Economic evaluations of donepezil’
(p. 81)]. Baseline data for the model cohort were
from a Danish epidemiological study (by Kronborg
Andersen and colleagues, 145 describing a
distribution of patients by severity (48%
moderately severe, 52% severe). The model starts
by assuming that all patients were autonomous
and living in the community.