Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review.
BACKGROUND
Alzheimer's disease is the most common cause of dementia and is characterised by an insidious onset and slow deterioration. The estimated prevalence of Alzheimer's disease for a standard health authority (500,000 people) is about 3330. Current service involves a wide range of agencies, and drug therapy for some patients.


OBJECTIVE
To provide a rapid and systematic review of the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine in the symptomatic treatment of people suffering from Alzheimer's disease.


METHODS
A systematic review of the literature was undertaken. METHODS - DATA SOURCES: Searches were made of electronic databases, including MEDLINE, EMBASE, The Cochrane Library, Database of Abstracts of Reviews of Effectiveness, NHS Economic Evaluation Database, National Research Register, Science Citation Index, BIOSIS, EconLit, MRC Trials database, Early Warning System, Current Controlled Trials, TOXLINE, Index of Scientific and Technical Proceedings, and Getting Easier Access to Reviews. All sources were searched over the period covered by the databases up to March/July 2000. Bibliographies of related papers were assessed for relevant studies and experts were contacted for advice and peer review, and to identify additional published and unpublished references. Manufacturer submissions to the National Institute for Clinical Excellence (NICE) were reviewed.


METHODS
Studies were included if they fulfilled the following criteria: (1) INTERVENTION: donepezil, rivastigmine or galantamine used to treat Alzheimer's disease. (2) PARTICIPANTS: people diagnosed with Alzheimer's disease who meet the criteria for treatment with donepezil, rivastigmine and galantamine. (3) OUTCOMES: measures assessing changes in cognition, function, behaviour and mood, quality of life (including studies assessing carer well-being and carer-input), and time to institutionalisation. (4) DESIGN: systematic reviews of randomised controlled trials (RCTs) and RCTs comparing donepezil, rivastigmine or galantamine with placebo or each other or non-drug comparators were included in the review of effectiveness. Economic studies of donepezil, rivastigmine or galantamine used to treat Alzheimer's disease that included a comparator (or placebo) and both the costs and consequence (outcomes) of treatment were included in the review of cost-effectiveness. Studies in non-English language, and abstracts and conference poster presentations of systematic reviews, RCTs and economic evaluations were excluded. Two reviewers identified studies by independently screening study titles and abstracts, and then by examining the full text of selected studies to decide inclusion. METHODS - DATA EXTRACTION AND QUALITY ASSESSMENT: Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer, with any disagreements resolved through discussion. The quality of RCTs was assessed using the Jadad scale and the quality of systematic reviews was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. The quality of economic evaluation studies was assessed by their internal validity (i.e. the methods used) using a standard checklist, and external validity (i.e. the generalisability of the economic study to the population of interest) using a series of relevant questions. METHODS - DATA SYNTHESIS: The clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine were synthesised through a narrative review with full tabulation of results of all included studies. In the economic evaluation, the reviewers assessed whether adjustments could be made to existing models to reflect the current situation in England and Wales. RESULTS - CLINICAL EFFECTIVENESS: (1) Donepezil--three systematic reviews and five RCTs (plus four studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that donepezil is beneficial when assessed using global and cognitive outcome measures. (2) Rivastigmine--three systematic reviews and five RCTs (plus two studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that rivastigmine is beneficial in terms of global outcome measures. (3) Galantamine--one systematic review and three RCTs (plus three studies from industry (unpublished data, submitted as commercial in confidence)) were found. Results suggest that galantamine is beneficial in terms of global, cognitive and functional scales. RESULTS - SUMMARY OF BENEFITS: It is difficult to quantify benefits from the evidence available in the literature. Statistically significant improvements in tests such as ADAS-cog (Alzheimer's Disease Assessment Scale cognitive subscale) may not be reflected in changes in daily life. (ABSTRACT TRUNCATED)
Clegg
A
A
Wessex Institute for Health Research and Development, University of Southampton, UK.
Bryant
J
J
Nicholson
T
T
McIntyre
L
L
De Broe
S
S
Gerard
K
K
Waugh
N
N
D000544:Alzheimer Disease / Q000188:drug therapy*; D002219:Carbamates / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D000077265:Donepezil; D005702:Galantamine / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000191:economics / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000191:economics / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000191:economics / Q000627:therapeutic use*; D048448:Phenylcarbamates; D010880:Piperidines / Q000191:economics / Q000627:therapeutic use*; D000068836:Rivastigmine
D002219:Carbamates; D007189:Indans; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine