Health Outcomes Research of Novel Disease Modifying Medications in Alzheimer’s Disease and Cost Burden of Early Onset Dementia

The main etiologies of dementia, a neurodegenerative disease, consist of: Alzheimer’s Disease (AD), Vascular Dementia (VD), Frontotemporal Lobar Dementia (FTD), and Lewy Body Dementia (LBD). AD the most common form of dementia is the sixth leading cause of death in the US, where currently 5.3 million Americans are diagnosed with Late-Onset and 95% of cases are 65 years and older. Early-Onset represents the remaining 5% of cases where ages at diagnosis is younger than 65 years. AD is characterized by a progressive loss of neurons with impact on patient cognition, function, and behavior. The 2015 Alzheimer’s Association Report estimated direct and indirect costs of AD and other dementias will reach $226 billion with an expected five-fold increase to $1.1 trillion by the year 2050. With no treatment available that stops, or slows down progression of the disease places the cost estimates of AD and dementia on top of the list of most expensive chronic diseases. The next generation of AD medications being investigated will target progression of the disease. Disease-modifying medications (DMMs) are being developed with a mechanism of action directed towards the main hallmarks found in AD patients: the amyloid-beta (Aβ) plaques, and the tau tangles. Tolfenamic acid, a non-steroidal anti-inflammatory (NSAID) drug, is being repurposed in the US as a DMM for AD treatment; human clinical trials still pending. Aducanumab, a monoclonal antibody, binds Aβ and increases its clearance; Phase III human clinical trials are in progress. DMMs are anticipated to improve cognition, function and behavior. The objectives, hypotheses, methods and results of this dissertation follow the manuscript format, and are three fold: Manuscript 1: The objective was to estimate cost-effectiveness of novel disease-modifying medication (DMM) compared to standard medication care currently used in the treatment of Alzheimer’s disease. The hypothesis was that the DMM option will show a favorable cost-effectiveness when compared to standard care. Using a Markov Model with a study population comprised of a hypothetical 1000 patients, 65 years and older, we evaluated quality life years (QALYs) gained by the new DMM and an appropriate price to develop a cost-effectiveness framework for the new product. In the Markov model we were able to determine an increase in QALYs when compared to standard of care with a cost value for DMM much higher than current standard care while still showing cost-effectiveness as a new treatment option. Manuscript 2: The objective was to determine affordability to payer’s