Donepezil, rivastigmine, galantamine and memantine for ...

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Economic analysis
respond to galantamine (with maintained or
improved cognition) after 6 months.
Cost-effectiveness of galantamine –
summary results
Appendix 14 presents summary findings on the
cost-effectiveness of galantamine across all
included studies. Studies generally report a picture
of cost savings (either full or partial) over time
with patient benefits in terms of a reduction in
time spent requiring FTC. A number of studies
report the mean gain in QALYs over time. 95,97,99
The findings from the UK cost-effectiveness study
are summarised below.
Ward and colleagues 99 in their UK CEA report
costs and benefits separately, showing patient
benefits as a reduction in time spent in FTC,
and/or a delay in requiring FTC with an
incremental 10-year cost. Ward and colleagues
calculate cost-effectiveness ratios (for 16-mg
galantamine treatment in mild to moderate AD),
stating that the incremental cost translates to £192
per discounted month of FTC avoided, or an
incremental cost per QALY of £8693 (detail on
these calculations is not presented but it has been
assumed that they used the undiscounted QALY
value per month of pre-FTC and FTC at 0.05 and
0.0283 respectively, a difference of 0.0217 QALY,
against the incremental cost of £192).
In subgroups for (1) patients with moderate AD
and (2) patients who respond to galantamine
treatment after 6-months, Ward and colleagues
predict a scenario of cost savings together with
additional benefits (reduced time in FTC).
Sensitivity analysis findings state that reducing the
proportion of patients needing FTC who were
admitted to an institution from 48 to 40% resulted
in a net cost per patient (16 mg) of £731 and a
reduction to 35% resulted in a net cost per patient
(16 mg) of £886. Varying the utility estimate by
±50% resulted in the estimated cost per QALY for
galantamine 16 mg ranging between £5810 and
£17,431. The results were reported to be nonsensitive
to changes in discount rate.
Industry submission on costeffectiveness
of galantamine
In their submission to the NICE technology
appraisal process, the manufacturer of
galantamine (Shire Pharmaceuticals and Johnson
and Johnson) presents CEA for galantamine (16
and 24 mg) plus usual care compared with usual
care alone. Their methodology follows that
outlined above, applying the AHEAD modelling
framework developed by Caro and colleagues 131 in
a UK context. The analysis and cost-effectiveness
results are as detailed in the published costeffectiveness
study by Ward and colleagues, 99
although the industry submission does contain
other supplementary detail on methods used and
findings. See Appendix 15 for an appraisal of the
modelling methodology.
The manufacturer’s submission reports that the
CEA predicts that the mean time to when FTC is
required for patients with similar characteristics to
those participating in the three clinical trials
(those used to populate their economic model) is
3.2 years and that the mean survival of these
patients is 5.1 years. For patients treated with
galantamine 16 mg/day, the delay to FTC is
2.5 months (2.63 months non-discounted) and for
galantamine at 24 mg/day the delay to FTC is
3.02 months (3.18 months non-discounted). They
estimate that this is equivalent to 0.06 and 0.07
QALY, respectively (non-discounted). Total costs
over time were £28,134 in the absence of
galantamine treatment, £28,615 for galantamine
16 mg/day and £28,806 for 24 mg/day.
The discounted incremental cost per QALY is
£8693 for galantamine 16 mg/day and £10,051
for galantamine 24 mg/day. The model predicted
net savings for patients with moderate AD
(MMSE < 18) and for those who showed response
to treatment after 6 months. Sensitivity analysis
showed that findings were sensitive to the relative
cost estimates for pre-FTC and FTC health states,
and the relative balance between institutional and
community-based care.
Comments on industry submission for
galantamine
The CEA in the industry submission for
galantamine largely reflects the published
literature discussed above. The model used
employs the methodology of the AHEAD model
by Caro and colleagues 131 (see Appendix 15 for an
outline appraisal of the industry model).
The structure of the model involves only two AD
states (i.e. pre-FTC and FTC) and this may be
seen as a crude reflection of the natural history of
AD. However, the health states used can be
regarded as those of interest, and may reflect a
more policy-orientated view of AD than plotting
stages of disease severity that are difficult to align
to policy relevant outcomes. The health states and
the mechanics of progression between health
states are not focused solely on cognition. The
model views the differences in disease progression
between galantamine treatment and non-