|Assessing the health and economic impact of galantamine treatment in patients with Alzheimer's disease in the health care systems of different countries
|Caro J, Salas M, Ward A, Getsios D, Migliaccio-Walle K, Garfield F
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
Galantamine was compared with placebo for the treatment of Alzheimer's disease in seven health care systems.
Economic study type
A hypothetical cohort of Alzheimer's patients was created by sampling from distributions taken from baseline data collected in three source trials (see 'Other Publications of Related Interest' below for bibliographic details). These patients were assigned characteristics such as age, gender, duration of disease and the presence of psychotic symptoms using data from the trials.
The setting was community care in Australia, Canada, Finland, New Zealand, Sweden, the Netherlands and the UK. The study was conducted in the USA.
Dates to which data relate
The effectiveness data were taken from trial data published in 2000. The costs were from 2001; any costs obtained before this were inflated using the medical inflation rate in each country and were converted to 2001 Euros.
Source of effectiveness data
The effectiveness data were derived from three clinical trials comparing galantamine with placebo.
A single model with two parts was used. The first part was a short-term model that predicted changes in cognitive function and psychotic symptoms on the basis of trial data. The second part used this information to predict time to requiring full-time care (FTC) and time to death. Full details of the model were not given, the reader being referred to another paper (see 'Other Publications of Related Interest' below for bibliographic details).
Outcomes assessed in the review
The outcomes assessed were:
the duration of disease,
cognitive level measured by the Alzheimer's Disease Assessment Scale - cognitive sub-scale (ADAS-cog),
the presence of psychotic symptoms, and
whether the patients have early-onset disease.
Study designs and other criteria for inclusion in the review
For details of the study designs, the readers were referred to other papers.
Sources searched to identify primary studies
Criteria used to ensure the validity of primary studies
Methods used to judge relevance and validity, and for extracting data
Number of primary studies included
Three primary studies were included in the review.
Methods of combining primary studies
Full details of the model were provided in an earlier paper. Characteristics were assigned to patients by sampling from distributions taken from the baseline data collected in the source trials.
Investigation of differences between primary studies
Results of the review
The baseline characteristics assigned to patients in the model were:
psychotic symptoms, 33.5%;
extrapyramidal symptoms, 6.2%; and
ADAS-cog, mean 27.0 (standard deviation 10.6)
Methods used to derive estimates of effectiveness
The cognitive level after 6 months was estimated using two regression equations that were derived from the trials. One related to the ADAS-cog of patients using galantamine and was modelled for patients who completed the 6 months of treatment. The second equation related to those on placebo. Patients who started on galantamine but discontinued were assumed to have had no treatment benefits, so their expected cognitive level was estimated using the placebo equation.
Estimates of effectiveness and key assumptions
The estimates were not reported.
Measure of benefits used in the economic analysis
The measures of benefit were time to FTC, time to death and quality-adjusted life-years (QALYs).
The costs were discounted at a rate of 3%. The costs were taken from published papers and were derived from a broad prospective. They comprised the costs of medical services and the costs relevant to stake holders such as providers of social services. The price year was 2001. Any costs obtained before this were inflated using the medical inflation rate in each country and then converted to 2001 Euros.
Statistical analysis of costs
No statistical analysis was undertaken.
The indirect costs were not included.
One-way sensitivity analyses were carried out on the cost of FTC, the proportion of patients requiring FTC who were in an institution, the discount rate and utility.
Estimated benefits used in the economic analysis
In the placebo group, the average time to FTC was predicted to be 3.2 years and average survival time was 5.1 years.
With galantamine the time to FTC was expected to increase by 6.8%.
These improvements were predicted to increase the QALY by 2%.
All values are mean net costs per patient over a decade with galantamine versus placebo. The mean net cost per patient over a decade was:
in Australia, a saving of Euro 26;
in Canada, a saving of Euro 1,227;
in Finland, an expense of Euro 1,313;
in New Zealand, a saving of Euro 3,494;
in Sweden, a saving of Euro 6,089;
in the Netherlands, a saving of Euro 2,150; and
in the UK, an expense of Euro 683.
Synthesis of costs and benefits
The costs and benefits were combined to give a cost per FTC month avoided.
In Finland, the discounted cost was less than Euro 553 (undiscounted cost less than Euro 499).
In the UK, the discounted cost was Euro 287 (undiscounted cost Euro 259).
Delaying full-time care (FTC) is predicted to reduce the costs of caring for highly dependent patients, whether care is delivered in the community or institutions. Interventions delaying the time when patients reach the state when FTC is needed can be expected not only to have health benefits and to reduce the daily burden for caregivers, but also to have the economic benefit of reducing the cost of care, or at least partially offsetting the cost of the treatment.
CRD COMMENTARY - Selection of comparators
Galantamine was compared with placebo. The rationale for this was clear. This treatment had been shown to improve cognitive function and to improve or maintain global function. Hence, it was compared with placebo in order to estimate the economic benefit of using the drug.
Validity of estimate of measure of effectiveness
The effectiveness data were taken from three clinical trials, details of which were provided in other papers (references given). Although some details of the baseline characteristics of the patients were reported, there was very little information on how these were derived, other than the fact that sampling was used. Only basic information pertaining to the effectiveness data for the second part of the model was reported: equations were used to derive a cognitive level after 6 months.
Validity of estimate of measure of benefit
The economic benefit was measured by QALYs, which were estimated using a decision model. These were derived from a study using caregivers as a proxy for patients with Alzheimer's disease. The total QALYs were calculated by adjusting the length of time in each health state in the model by the utility value for the health state.
Validity of estimate of costs
The costs were determined from a perspective somewhat broader than that of a comprehensive payer, including social services. The source of the cost data was appropriately reported, although full details of the costs were not included. Details on how the costs from previous years were converted to 2001 were given, as were details on how these were converted to Euros to enable comparisons across the countries studied. The price year was reported, which would assist any future reflation exercise.
The authors made no comparisons with other studies. They acknowledged the limitations of the study. For example, the assumption of a constant drug effect over time and the use of a population from a clinical trial that may not represent the general population. Sensitivity analyses were conducted, which further increase the external validity of the analysis.
Implications of the study
The authors suggested that further research is needed. This should include productivity and indirect costs to society in general, and determine the long-term effect of galantamine on time to FTC.
Source of funding
Supported in part by Johnson & Johnson Pharmaceutical Research and Development L.L.C.
Caro J, Salas M, Ward A, Getsios D, Migliaccio-Walle K, Garfield F. Assessing the health and economic impact of galantamine treatment in patients with Alzheimer's disease in the health care systems of different countries. Drugs and Aging 2004; 21(10): 677-686
Other publications of related interest
Raskind MA, Peskind ER, Wessel T, et al. Galantamine in AD: a 6 month randomized, placebo-controlled trial with a 6 month extension. Neurology 2000;54:2261-8.
Tariot PN, Solomon PR, Morris JC, et al. A 5 month randomized, placebo-controlled trial of galantamine in AD. Neurology 2000;54:2269-76.
Wilcock GK, Lilienfeld S, Gaens E, et al. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentred randomised controlled trial. BMJ 2000;321:1-7.
Subject indexing assigned by NLM
Alzheimer Disease /drug therapy /economics; Australasia; Canada; Cost-Benefit Analysis /economics; Delivery of Health Care /economics; Europe; Galantamine /economics /therapeutic use; Humans; Long-Term Care /economics; Models, Economic; Placebos /economics
Date bibliographic record published
Date abstract record published