Donepezil, rivastigmine, galantamine and memantine for ...

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Economic analysis
donepezil, rivastigmine and galantamine using the
industry models submitted to NICE’ (p. 131).
Summary of published systematic
reviews that offer a broader
reporting on the costeffectiveness
of donepezil,
rivastigmine and galantamine
Best evidence syntheses of data on the efficacy and
cost-effectiveness of donepezil and rivastigmine
have been conducted by the Wessex Institute for
Health Research and Development (WIHRD) in
2001 on behalf of the NHS R&D HTA programme
in the UK 1,136 and by the Canadian Coordinating
Office for Health Technology Assessment
(CCOHTA) in 2000. 78,108,137 The studies included
in the economic evaluation sections of the two
reports were almost identical. The WIHRD report
included five economic evaluations of
donepezil 81,82,84–86 and four economic evaluations
of rivastigmine. 90–93 Two unpublished reports
prepared for NHS committees, one on donepezil
and one on rivastigmine, 81,90 were absent from the
CCOHTA report. The CCOHTA report included
eight evaluations of donepezil 82–86,138,139,140 and
three of rivastigmine. 91–93 Three studies on
donepezil 138–140 which were included in the
CCOHTA report were absent from the WIHRD
report because a priori criteria meant that
abstracts 140 were excluded and required that both
costs and consequences be reported (the other two
studies 138,139 reported costs only). The last two
studies are also excluded from this report for the
same reasons and although abstracts are included
these are only briefly reported on.
The WIHRD report was conducted from the
perspective of the NHS and PSS. WIHRD
reported that cost-effectiveness base-case estimates
in the five evaluations of donepezil all
demonstrated increased effectiveness associated
with cost saving in two studies but being more
costly in the other three. In addition, subgroup
and sensitivity analyses led to wide fluctuations in
cost-effectiveness estimates which WIHRD thought
cast doubt on the robustness of these estimates,
particularly as some of the subgroup analyses led
to conflicting results between studies. The
evaluations of rivastigmine were difficult to
interpret because overall effectiveness was not
reported in two studies and because these studies
did not include drug therapy costs. Costeffectiveness
ratios could not be extracted from
these two studies. 91,92 The report concluded that
there was great uncertainty surrounding the costeffectiveness
of donepezil and rivastigmine.
The CCOHTA report reviewed donepezil and
rivastigmine because these were the only agents
licensed for use in Canada for the treatment of
mild-to-moderate AD at the time of the report.
Of the seven donepezil studies considered,
donepezil was the dominant strategy in three, in
two was cost neutral and in the remaining two
donepezil treatment was associated with increased
costs coupled with increased benefits. In contrast,
all the studies of rivastigmine reported cost
savings. The authors of the report concluded that
donepezil and rivastigmine were both associated
with either a slight increase or slight decrease in
overall costs coupled with a better clinical
outcome for patients in the mild-to-moderate AD
category. It was acknowledged, however, that
gains of time in a non-severe AD state were very
small even in the most optimistic of scenarios. In
addition, the cost savings predicted by the models
occurred primarily because of a reduction in
informal care costs and delays in
institutionalisation. The CCOHTA report authors
felt that the former was difficult to measure and
that the drugs in question had not been proved to
impact significantly on the latter. Given that the
models were based on short-term efficacy data
rather than effectiveness data, the results could be
viewed as speculative.
Economic evaluations of
memantine
Characteristics of economic evaluations
Table 53 provides a summary of the study
characteristics for the five economic evaluations
reporting on the cost-effectiveness of
memantine. 100–104 The studies represent countryspecific
analyses for Finland, Norway, Spain and
the UK, with a broadly similar methodology
applied across all studies. Table 53 reports the
‘headline’ finding across studies of an
improvement in time in autonomy (time spent in
state defined as independent) together with cost
savings over time (2 years104 to 5 years) 100–103 (four
of these studies reflect a societal perspective).
Further detail on study findings from François and
colleagues103 and Jones and colleagues104 is
provided in Appendix 14, with detail on study
characteristics and methods presented in
Appendix 13. However, further detail on study
findings, characteristics and methods is not
provided for those studies available only as
abstracts.