Economic evaluation of treatments for Alzheimer´s disease

Sammanfattning: Alzheimer´s disease (AD) is the most common cause of dementia, leading to progressive cognitive impairment and loss of functional abilities for die afflicted patient, a heavy burden on caregivers and high costs for society. New treatment strategies are being introduced setting focus on the need to make informed decisions on the allocation of resources to and within dementia care. This thesis develops a method for economic evaluation of treatments for AD and estimates the cost-effectiveness of existing and hypothetical interventions aimed at alleviating symptoms and slowing the progression of AD. Study I investigated the relationship between cognitive impairment, measured by the MiniMental State Examination (MMSE), and costs of formal care based on the Kungsholmen Project - a longitudinal population-based survey of subjects aged 75 years and above in Stockholm, Sweden. Costs for special accommodation, home help, and pharmaceuticals were estimated for patients in different MMSE states and the total cost of care was simulated for a cohort of patients over a period of 5 years. In a linear regression model controlling for age and gender, a decrease by 1 point in MMSE score was associated with an increase in annual costs by 15 000 SEK. Study II estimated the impact on costs of care from treatment of patients with mild to moderate AD with the cholinesterase inhibitor donepezil. A Markov model was used to simulate the progressive cognitive impairment of a cohort of AD patients, based on Kungsholmen. Project data on costs and transition probabilities. Treatment effectiveness rates were derived from a clinical trial; donepezil caused a decrease in transition probabilities to more severe disease states by 46% (5 mg daily) or 48% (10 mg daily). Over a 5-year time period, treatment with donepezil was estimated to reduce the total cost of care by about 20 000 SEK, or 3% of total costs. Treatment was cost-neutral or cost saving in all scenarios investigated. Study III analysed the costs of medical care, community care and informal care for 272 AD patients and their caregivers in Sweden, Denmark, Norway and Finland. Data was collected by questionnaires at baseline, after 6 months and again after 12 months. Average annual costs ranged from 60 700 SEK (MMSE >25) to 375 000 SEK (MMSE<10). Costs for community care constitute about half of total costs of care and increase sharply with increasing cognitive impairment. Informal care costs, valued at the opportunity cost of the caregiver's time, make up about a third of total costs and also increased significantly with disease severity. Regression analysis confirmed a strong association between costs and cognitive function; between as well as within individuals over time. There was also a significant influence on costs from behavioural disturbances, assessed with a brief version of the neuropsychiatric inventory (NPI). Study IV estimated the utility in different stages of AD using published population weights for the EuroQoL instrument. Patients rated their own utility to on average 0.833 with little variation across severity levels. Proxy-rated utility ranged from 0.690 (MMSE >25), to 0.329 (MMSE<10). Proxy-rated utility, as well as changes in utilities over time, were significantly related to MMSE scores and inversely related to scores on the brief NPI and institutionalisation. Utility estimates were highly correlated with the disease-specific quality of life instrument QoL-AD. In conclusion, the thesis shows that costs for community care, informal care and total costs of care increase, while proxy-rated utility and quality of life decrease with the degree of cognitive impairment in AD patients. The model simulations show that even modest and short-term effects on the progression of AD can be associated with important costsavings and gains in quality-adjusted life-years.