Cost-utility analysis in Alzheimer's disease

Sammanfattning: Alzheimer's disease (AD) is a neurodegenerative disorder causing dementia, a syndrome of gradual loss of cognitive function causing impairment in social and occupational functioning. This leads to substantial loss in quality of life and premature death for persons with the disease, associated suffering for their families and large costs to society. In parallel to the aging of the population the world prevalence is predicted to threefold within the next 40 years, creating a challenge for researchers and decision-makers to make better treatments available. Further, improved methods for economic evaluation in AD are needed to identify the optimal treatment strategies. The overall objective of this thesis is to explore the application of cost-utility analysis in AD and address key methodological challenges and data needs. In paper I, prediction functions for simulating disease progression and economic endpoints in a decision-analytic model were estimated. Three year follow-up data from the Swedish Alzheimer Treatment Study (SATS) on the natural course of AD of 435 patients commencing treatment with donepezil and their care setting and costs of care was analyzed. A simplified model in which cognition (representing the underlying course of disease) and the ability to perform activities of daily living (ADL) (representing patient care need) was assumed to predict the provision of care. According to the estimated statistical functions, cognition was found to be the key predictor of ADL-ability which itself was the main predictor of care setting and costs of care. In paper II, we used contingent valuation methods to elicit caregivers willingness-to-pay (WTP) for reductions in patient care need. In total, 517 caregivers of AD patients in four countries (Spain, Sweden, UK and US) were interviewed. The mean WTP for a one hour reduction per day was estimated at between £59 and £144 per month depending on country. The income of the caregiver was the only consistently significant determinant of WTP across all countries. In paper III, we assessed predictors of the costs of care of 1,222 AD patients in four countries (Spain, Sweden, UK and US), both residing in the community and in residential care settings. Cognition, ADL-ability, behavioural symptoms and costs of care (RUD-Lite) were assessed via a patient and caregiver interview. Cost estimates ranged between £1,000 to £5,000 per patient and month, increasing with disease severity and higher in residential care settings. ADL-ability was the most important predictor of costs but part of the variation was also explained by cognition and behavioural symptoms. In paper IV, the key components and drivers of costs of care in a clinical trial sample of 2,744 mild to moderate AD patients were identified. Costs were assessed with RUD-Lite at baseline and every 6 months over the 18 months trial. Informal care constituted 82-86 percent of total costs, whereas community care and patient accommodation constituted an equal share of 12-16 percent. Informal care also had the strongest correlation with disease severity measures including cognition, ADL-ability, global function and behavioural symptoms. In conclusion, cognition, ADL-ability and behavioural symptoms are all important indicators of care need in AD and should be considered in economic modelling. Caregivers have a substantial willingness to pay for reductions in care need. Informal care is the key cost component in clinical trials in mild to moderate AD. Health utility estimates of AD patients are highly dependent on the methodology including choice of instrument, respondent and utility tariffs.