Donepezil, rivastigmine, galantamine and memantine for ...

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102 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included five economic evaluations of donepezil 81,82,84–86 and four economic evaluations of rivastigmine. 90–93 Two unpublished reports prepared for NHS committees, one on donepezil and one on rivastigmine, 81,90 were absent from the CCOHTA report.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.
TABLE 53 Characteristics of economic evaluation studies for memantine Estimation of outcomes within economic evaluations (memantine) All of the studies use a modelling approach to consider disease progression over time. Studies report that disease progression was modelled over time (2 or 5 years) in patients with moderately severe and severe AD, based on severity level, dependency level and care setting. Data on modelling methods are limited in the published abstracts so it is not possible to offer further detail here. However, from the published abstracts it appears that all studies followed a similar disease progression modelling method to that described in the studies by François and colleagues 103 and Jones and colleagues, 104 which is described below. François and colleagues’/Jones and colleagues’ model of AD progression (memantine) Jones and colleagues 104 report on the costeffectiveness of memantine versus no pharmacological treatment using a Markov-type model of disease progression through health states (13 states including death) defined according to a combination of cognitive function (using MMSE score), physical dependency (either dependent or independent) and place of residency (either community or institution). For disease severity, moderate AD is defined using an MMSE score of >14, moderately severe AD is © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 1 Characteristic Guilhaume Launois et al. 101 Antonanzas François et al. 103 Jones et al. 104 et al. 100 et al. 102 Publication year 2003 (abstract) 2003 (abstract/poster) 2003 (abstract) 2004 2004 Country setting Finland Norway Spain Finland UK Base year prices Not stated Not stated Not stated 2001 (€) 2003 (UK£) Intervention Memantine Memantine 20 mg Memantine Memantine Memantine Study type CEA model CEA model CEA model CEA model CEA model Study group – AD Moderately Moderately Moderately Moderately Moderately severe severe and severe severe and severe severe and severe severe and severe and severe Perspective Stated – societal Stated – societal Stated – societal Stated – societal Not stated – perspective perspective perspective perspective appears to be NHS and PSS Industry role Not stated. Study funded by Not stated. Study funded by Study funded by Authorship manufacturer Authorship manufacturer manufacturer included included manufacturer manufacturer Study base-case Improvement in Improvement in Improvement in Improvement in Improvement in ‘headline’ time spent in time in autonomy, time in autonomy, time spent in time spent in predictions/findings independent state, cost saving cost saving independent state, independent state, and cost saving (5 years) (5 years) cost saving cost saving (5 years) (5 years) (2 years) defined as an MMSE of 10–14 and severe disease is defined as MMSE of
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Health Technology Assessment 2006;
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The clinical and cost-effectiveness
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Objectives: To provide an update re
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List of abbreviations .............
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AChEI acetylcholinesterase inhibito
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Epidemiology and background Alzheim
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Galantamine Five published economic
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Description of underlying health pr
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TABLE 1 Estimated prevalence of AD
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as one component of their care. A n
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The a priori methods used for syste
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Data synthesis Data were synthesise
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14 Clinical effectiveness TABLE 3 C
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16 Clinical effectiveness TABLE 3 C
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18 Clinical effectiveness particula
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20 Clinical effectiveness Compariso
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22 Clinical effectiveness TABLE 6 M
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24 Clinical effectiveness donepezil
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32 Clinical effectiveness DAD The D
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34 Clinical effectiveness clinical
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36 Clinical effectiveness TABLE 10
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40 Clinical effectiveness statistic
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46 Clinical effectiveness Summary:
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48 Clinical effectiveness differenc
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1. Clegg A, Bryant J, Nicholson T,
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placebo-controlled study of donepez
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94. Brooks E, Deal L. The effect of
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of memantine in patients with moder
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376 Health Technology Assessment Pr
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