Donepezil, rivastigmine, galantamine and memantine for ...

outcome. The incremental cost per extra year in a
non-severe AD health state was £7047 for the 5-mg
dose versus placebo and £5697 for the 10-mg dose
versus placebo. The incremental cost per extra
year in a non-severe health state for the 10-mg
dose versus the 5-mg dose was £4450. For those
patients with moderate AD at the start of the
model the expected 5-year cumulative costs per
patient were £45,719 for the placebo cohort,
£46,193 for the donepezil 5-mg treatment cohort
and £46,716 for the donepezil 10-mg treatment
cohort.
The AD2000 Collaborative Group 43 collected
resource use data prospectively as part of the trial
in order to calculate an average annual cost per
patient. Data are reported against 11 formal
health and social services. Cost estimates do not
include the cost for donepezil or costs associated
with institutionalisation. Although not explicitly
stated, costs are presented as 2000£. The reported
estimated annual cost per patient resident in the
community in the donepezil group was £2842 and
in the placebo group £2344; the annual additional
cost with donepezil was £498 (–193 to 1189). Cost
estimates are not presented separately by dose but
authors report that the costs (of care) for 5-mg
donepezil were £445 higher than the 10-mg dose.
None of the differences on resource use (or cost)
were statistically significant
Cost-effectiveness of donepezil –
summary results
Appendix 14 presents summary findings on the
cost-effectiveness of donepezil across all included
studies. Studies generally report cost savings over
time with patient benefits in terms of a delay in
disease progression (using MMSE scores to define
stages of disease severity), with more time spent in
the less severe AD health states. However, many of
the studies report findings based on a societal
perspective, including patient and caregiver costs.
The findings from the UK cost-effectiveness
studies are summarised below.
Stein 81 presents costs per QALY estimates based
on applying only drug costs. A gain of between
0.05 and 0.08 QALYs is estimated based on
assumptions for the level of benefits gained from
treatment. A cost per QALY of £34,640 is
predicted for a 5 mg/day dose over 2 years when
treatment is assumed to give a benefit equivalent
to 0.05 QALY, rising to £79,560 for 5 years,
£117,280 for 8 years and to £139,020 for 10 years.
Increasing the benefit to 0.08 QALY reduces the
cost per QALY to £21,383 over 2 years, rising to
£85,815 for 10 years of treatment. Stein also
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Health Technology Assessment 2006; Vol. 10: No. 1
provides cost–utility estimates for a 10 mg/day
dose of donepezil stating that the evidence for
marginal benefit over the 5 mg/day dose is less
clear than the evidence for the dis-benefits that
are associated with the higher dose. With an
assumed benefit of 0.05 QALY the cost per QALY
of a 10 mg/day dose is £48,500 over 2 years of
treatment, rising to £194,720 for 10 years. The
higher QALY gain assumption of 0.08 reduces the
cost per QALY to £29,938 for 2 years and
£120,198 for 10 years.
Stewart and colleagues 82 present results as
incremental investment in treatment required to
achieve an extra year spent in a non-severe AD
state. Treatment groups are described as being
almost cost neutral over the 5-year time horizon as
costs are raised only very slightly. Two treatment
groups are considered: patients who have mild AD
at the start of treatment and patients who have
moderate AD at the start of treatment. For
patients with mild AD who are treated with
donepezil at the 10-mg dose, an incremental cost
(over placebo) of £5698 is required to obtain an
extra year in a non-severe AD state and the
incremental cost versus the 5-mg dose is £4451.
For patients with mild AD who are treated with the
lower 5-mg dose an incremental cost (over
placebo) of £7048 is required to obtain an extra
year in a non-severe AD state. If the patients
entering the model have moderate AD then an
incremental cost (over placebo) of £3562 is
required to obtain an extra year in a non-severe
AD state when they are treated with a 10-mg dose
and there is no incremental benefit versus the
5-mg donepezil dose. If they are treated with the
5-mg dose an incremental cost (over placebo) of
£1210 is required to obtain an extra year in a nonsevere
AD state.
Stewart and colleagues 82 also ran sensitivity
analyses in which some parameter inputs for the
model were altered. They report that variations in
the discount rate do not cause any alteration in
the relative positions of the AD subgroups. A lower
mortality rate (30% over 3 years) which leads to
more patients remaining alive at later stages and
continuing to incur costs was also tested. With this
lower mortality rate the incremental costs (over
placebo) for an additional year in a non-severe AD
state reduce slightly to £4955 and £5328 for the
10- and 5-mg donepezil groups, respectively, in
mild AD. In moderate AD the incremental costs
for the 10- and 5-mg doses are £3372 and £942,
respectively. No other sensitivity analyses are
reported.
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