Background: Recommendations in the UK suggest restricting treatment of Alzheimer’s disease with cholinesterase inhibitors, on cost-effectiveness grounds, to patients with moderate cognitive decline. As the economic analyses that informed these recommendations have been the subject of debate, we sought to address the potential limitations of existing models and produce estimates of donepezil treatment cost effectiveness in the UK using the most recent available data and simulation techniques.
Methods: A discrete-event simulation was developed that predicts progression of Alzheimer’s disease through correlated changes in cognition, behavioural disturbance and function. Patient-level data from seven randomized, placebo-controlled donepezil trials and a 7-year follow-up registry provided the basis for modeling longitudinal outcomes. Individuals in the simulation were assigned unique demographic and clinical characteristics and then followed for 10 years, with severity of disease tracked on continuous scales. Patient mix and costs were developed from UK-specific literature. Analyses were run for severity subgroups to evaluate outcomes for sub-populations with disease of mild versus moderate severity from both a healthcare payer and societal perspective. All costs are reported in £, year 2007 values, and all outcomes are discounted at 3.5% per annum.
Results: Over 10 years, treatment of all patients with mild to moderate disease reduces overall direct medical costs by an average of over £2300 per patient. When unpaid caregiver time is also taken into consideration, savings increase to over £4700 per patient. Compared with untreated patients, patients receiving donepezil experience a discounted gain in QALYs averaging 0.11, with their caregivers gaining, on average, 0.01 QALYs. For the subset of patients starting treatment with more severe disease, savings are more modest, averaging about £1600 and £3750 from healthcare and societal perspectives, respectively. In probabilistic sensitivity analyses, donepezil dominated no treatment between 57% and 62% of replications when only medical costs were considered, and between 74% and 79% of replications when indirect costs were included, with results more favourable for treatment initiation in the mild versus moderate severity stages of the disease.
Conclusions: Although the simulation results are not definitive, they suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer’s disease in the UK. They also indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer’s disease.
Cholinesterase Inhibitor Probabilistic Sensitivity Analysis Supplemental Digital Content Patient Care Cost Discrete Health State
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All authors participated in the conception and design of the economic model and analyses, and in the writing of the manuscript. Denis Getsios was the lead investigator and provided the detailed specifications on the model design, directed implementation and oversaw the programming. Steve Blume assisted with design of the model, data analyses and development of the model inputs and directed the analyses. Jack Ishak directed the design and implementation of the data analyses for development of model input data. Grant Maclaine assisted in the design of the model, review and collection of the model input data, and specification of the analyses. This work was supported by an unrestricted grant from Eisai Ltd.
The authors thank Ye Tan for biostatistical support, Luis Hernandez for his involvement in programming the model and Sunning Tao for running the economic analyses and assisting in the production of the manuscript.
Grant Maclaine is an employee of Eisai Europe Limited, the sponsor of the research. The remaining authors are employees of United BioSource Corporation, a firm consulting to Eisai and other pharmaceutical manufacturers who market medications for treating Alzheimer’s disease.
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