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The cost-benefit of cholinesterase inhibitors in mild to moderate dementia: a willingness-to-pay approach |
Wu G, Lanctot K L, Herrmann N, Moosa S, Oh P I |
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Record Status 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. Health technology The use of cholinesterase inhibitors in mild to moderate dementia.
Study population The study population comprised non-professional caregivers of outpatients with mild to moderate dementia living in the Toronto (Canada) area, and who were attending appointments in the Geriatric Psychiatry Department and Women's College Health Science Centre, Toronto, Canada.
Setting The setting was primary care. The economic study was carried out in Toronto, Canada.
Dates to which data relate The dates to which the effectiveness data related were not specified. The price year was 1999.
Source of effectiveness data The effectiveness data were derived from a single study.
Link between effectiveness and cost data The costing was not based on the same sample as that used in the effectiveness study. It represented the yearly cost of the cholinesterase inhibitors, as stated in the Ontario Drug Benefit Formulary (2002).
Study sample No power calculations to determine the sample size were reported and no specific sample size seems to have been planned. The caregivers were sought consecutively from a cohort of patient-caregiver dyads attending appointments in two outpatient centres. Potential study participants were identified and approached in person, following their appointments, to assess their willingness to participate. Thirty-three patient-caregiver dyads were approached, of which five declined to participate (two refused and the other three declined due to scheduling problems). Hence, the study sample consisted of 28 non-professional caregivers. The mean age of the caregivers was 66.32 (+/- 14.32) years, whilst that of the patients was 78.29 (+/- 4.31) years. Seventy-five per cent of all caregivers and 32.1% of patients were females.
Study design This was a cohort study that was carried out in two centres. Neither the caregivers nor the patients were followed-up in the study, as only caregivers had to complete a WTP questionnaire at the time of interview. In the interview and questionnaire, the caregivers were blind to the identity of the drug class in order to avoid bias from prior experience with cholinesterase inhibitors.
Analysis of effectiveness All the caregivers included in the study were accounted for in the analysis. The outcome used in the analysis was the caregiver's WTP for using a cholinesterase inhibitor to delay disease progression and to treat the behavioural symptoms of dementia in patients with AD. The investigators interviewed caregivers for approximately 45 minutes. In the first part of the interview, demographic information was obtained for every patient-caregiver dyad. In the second part of the interview, the caregivers were presented with a fictional situation and asked what was the maximum amount of money they would be willing to pay to delay the progression of the disease. In order to do so, the caregivers were presented with four scenarios.
Scenario A. The hypothetical patient was described as having mild AD without behavioural symptoms, which was stabilised over one year of treatment with a cholinesterase inhibitor. The caregivers were also presented with what would happen without the cholinesterase inhibitor.
Scenario A with adverse effects. The hypothetical patient experienced significant but tolerable adverse effects related to the cholinesterase inhibitor. These included gastrointestinal adverse effects, dizziness and unsteadiness.
Scenario B. The hypothetical patient was described as having mild AD with behavioural and psychological symptoms of dementia, including verbal outburst, aggressiveness during care and anxiety. Stabilisation in both cognitive and behavioural realms occurred with cholinesterase inhibitors over one year of treatment.
Scenario B with adverse effects. The hypothetical patient experienced the same effects as in the second scenario.
For each scenario, the caregiver was asked what amount (or range) he/ or she was willing to pay to buy the medication assuming he or she was the caregiver of the hypothetical patient. The WTP was elicited using a ping-pong methodology to reach an upper and lower limit using seven pre-set ranges. Once the range was known, the caregiver was asked to derive a specific amount in that range. Regression analyses, to assess the relationship between demographic data (including caregivers' yearly income) and the WTP, were undertaken.
Effectiveness results The mean yearly WTP was Can$4,540 (95% confidence interval, CI: 2,334 - 6,749) for scenario A, Can$3,686 (95% CI: 1,530 - 5,842) for scenario A with adverse effects, Can$5,003 (95% CI: 2,661 - 7,345) for scenario B, and Can$4,486 (95% CI: 2,222 - 6,750) for scenario B with adverse effects. The difference between scenario A and A with adverse effects was significant, (p=0.04).
The results from the Wilcoxon signed ranks test showed that the presence of adverse effects influenced the WTP significantly for both scenarios A and B, in the direction expected (pay less for scenario A and more for scenario B).
The results from multivariate regression analyses demonstrated that the subject's (caregiver's family) yearly income was the only significant predictor of WTP in all scenarios.
Clinical conclusions Caregivers were willing to pay more for cholinesterase inhibitors when AD was associated with behavioural and psychological symptoms. Yearly income was the demographic variable that significantly predicted WTP.
Measure of benefits used in the economic analysis The benefit measure used was monetary benefits, as derived using the WTP method reported already.
Direct costs The resource use quantities and the unit costs were not reported separately. The direct costs to the caregiver were included in the analysis, which only included the costs of the cholinesterase inhibitors. The yearly cost of the cholinesterase inhibitors was derived from the Ontario Drug Benefit Formulary 2002. This cost was irrespective of the drug and dose used. In Canada, cholinesterase inhibitors have been priced such that total daily acquisition cost is the same irrespective of the drug and dose used. Discounting was not relevant since all the costs were incurred during one year. The study reported the average costs. The price year was 1999.
Statistical analysis of costs The costs were treated as point estimates (i.e. the data were deterministic).
Indirect Costs The indirect costs were not included in the study.
Sensitivity analysis From the regression analyses, the authors predicted the mean WTP for the Canadian general population and the elderly population using data on incomes from Statistics Canada. These predicted WTPs were then compared with the cost of cholinesterase inhibitors.
Estimated benefits used in the economic analysis The mean yearly WTP was Can$4,540 (95% CI: 2,334 - 6,749) for scenario A, Can$3,686 (95% CI: 1,530 - 5,842) for scenario A with adverse effects, Can$5,003 (95% CI: 2,661 - 7,345) for scenario B, and Can$4,486 (95% CI: 2,222 - 6,750) for scenario B with adverse effects.
Cost results The yearly cost of the cholinesterase inhibitors was Can$1,675.
Synthesis of costs and benefits The costs and benefits were combined in the form of the net benefit, where the net benefit is equal to the WTP minus the cost of cholinesterase inhibitors. The net benefit using mean yearly income from the study sample was Can$2,858 for scenario A, Can$2,006 for scenario A with adverse effects, Can$3,318 for scenario B, and Can$2,796 for scenario B with adverse effects.
Using the 1995 Canadian national household average income, the net benefit was Can$3,840 for scenario A, Can$2,903 for scenario A with adverse effects, Can$4,508 for scenario B, and Can$3,807 for scenario B with adverse effects.
Using the 1999 Canadian elderly family average income, the net benefit was Can$2,547 for scenario A, Can$1,723 for scenario A with adverse effects, Can$2,941 for scenario B, and Can$2,476 for scenario B with adverse effects.
Authors' conclusions The results of the study suggested that the willingness-to-pay (WTP) for the treatment of mild to moderate dementia was higher than the cost of cholinesterase inhibitors, even when the adverse effects of the drugs were taken into consideration. This indicated, therefore, a net benefit for cholinesterase inhibitors in the treatment of dementia.
CRD COMMENTARY - Selection of comparators It is unclear why the comparator used (no treatment) was chosen, as the authors did not report if there were other treatments, other than cholinesterase inhibitors, available for dementia. Further to correspondence with the authors, we have been advised that, at present, no other treatments are currently approved for mild to moderate Alzheimer's disease in Canada. You should decide if this is a widely used health technology in your own setting.
Validity of estimate of measure of effectiveness The analysis was based on the responses of a cohort of caregivers in order to obtain WTP estimates for cholinesterase inhibitors. This approach was appropriate for the study question. The study sample was representative of the study population since all the participants were caregivers of people suffering from dementia. However, the study sample was very small, consisting only of 28 participants. Hence, it is unsurprising that only one factor (yearly income) significantly predicted WTP in the regression analysis. The four scenarios depicted compared the effects of cholinesterase inhibitors and the effects of no treatment, with participants being asked to derive the maximum they would be willing to pay for treatment. Even though the authors referenced the literature from where the effects of cholinesterase inhibitors were derived, more information on how this literature search was undertaken and the quality of the studies retrieved (amongst other factors) should have been included, to increase the internal validity of the study. The authors undertook appropriate statistical analyses to account for predictors of WTP (such as yearly income).
Validity of estimate of measure of benefit The estimation of benefits was obtained directly from the effectiveness analysis. The choice of monetary benefits was justified, as this study was a cost-benefit analysis.
Validity of estimate of costs All the categories of cost relevant to the perspective adopted were included in the analysis. On the cost side, the authors did not include the costs borne by the caregivers of dementia patients. However, this would seem to be appropriate since the benefits of cholinesterase inhibitors (e.g. reduced burden on the caregivers due to stabilisation in dementia patients) would have been picked in the WTP estimates given by the caregivers. Hence, including these costs would have been double counting. Even though the cost of medications is reimbursed in Canada, these were included as the only cost because, in the questionnaire, the participants were told to imagine they had to pay for the medication themselves. Other relevant direct costs, such as personnel and physician visits, equipment costs, and cost-savings attributed to the reduction in symptoms due to cholinesterase inhibitors, were not included in the analysis. These omissions would most likely lead to the underestimation of the net benefit of using cholinesterase inhibitors.
The costs and the quantities were not reported separately, which will hamper the generalisability of the authors' results to other settings. Moreover, a gross yearly cost was used, irrespective of the drug and dose. Further to correspondence with the authors, we have been advised that, "in Canada, cholinesterase inhibitors have been priced such that total daily acquisition cost is the same irrespective of the drug and dose used". No sensitivity analyses of these costs were performed, which will limit the interpretation of the study findings and hamper generalisability to other settings.
Other issues The authors made appropriate comparisons of their findings with those from other studies that also found cholinesterase inhibitors to be effective treatments for mild to moderate AD, providing long-term health and economic benefits for patients, caregivers and payers. The authors partly addressed the issue of generalisability to other settings when they estimated the impact of income on WTP using regression analysis, and then used the mean income of the Canadian general population and that of the elderly population. However, the authors warned readers about the generalisability of these results, as the impact of income on WTP was derived from a very small sample of 28 participants. Further, the authors acknowledged that, because Canadians do not pay for medications directly, the stated WTP might exceed the actual WTP. The authors, as they themselves acknowledged, did not specify the probability of obtaining the beneficial health outcomes of cholinesterase inhibitors, with only a percentage of patients obtaining the health benefits outlined in the questionnaire. The authors' conclusions reflected the scope of the analysis.
The authors reported a number of further limitations to their study. First, the design of contingent valuation studies such as this one has to encompass all the three essential dimensions. Second, the outcomes beyond health benefit were not explicitly presented in the four scenarios. However, the authors believed that the participants implicitly understood these other benefits, and based their estimates accordingly. The authors also failed to conduct pre-tests to ensure that the caregivers understood the scenarios. However, because the participants were familiar with the disease, and were interviewed in a one-to-one fashion, they appeared to indicate an understanding of the scenarios.
Implications of the study The authors reported that this study was an initial attempt to use the WTP approach to address the health economics of cholinesterase inhibitors. The authors stated that further WTP studies are needed to better elucidate the economic value of cholinesterase inhibitors. Such studies should use more refined methodology, and larger and more representative samples from different regions and countries.
Source of funding Supported by a United States Pharmacopoeia Information Development award.
Bibliographic details Wu G, Lanctot K L, Herrmann N, Moosa S, Oh P I. The cost-benefit of cholinesterase inhibitors in mild to moderate dementia: a willingness-to-pay approach. CNS Drugs 2003; 17(14): 1045-1057 Other publications of related interest Fillit H, Gutterman EM, Brooks RL. Donepezil use in managed Medicare: effect on health care costs and utilisation. Clinical Therapeutics 1999;21:2173-85.
Cummings JL, Duttagupta S, Wade S, et al. Cost savings associated with donepezil use for Alzheimer's disease patients in managed care. American Journal of Geriatric Psychiatry 2001;9(3 Suppl 1):53.
O'Brien BJ, Novosel S, Torrance G, et al. Assessing the economic value of a new antidepressant: a willingness-to-pay approach. Pharmacoeconomics 1995;8:34-45.
Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Aged, 80 and over; Caregivers /economics; Cholinesterase Inhibitors /adverse effects /economics /therapeutic use; Cost-Benefit Analysis; Dementia /drug therapy /economics; Demography; Female; Health Care Costs; Health Services Research; Humans; Male; Middle Aged; Patient Satisfaction /economics; Surveys and Questionnaires AccessionNumber 22003001556 Date bibliographic record published 30/11/2004 Date abstract record published 30/11/2004 |
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