Biomarker based adaptive development in Alzheimer disease.

Today, more than 46 million people worldwide are living with dementia (Wimo et al., 2013). This number will almost double every 20 years, with an estimated 74 million in 2030 and 131 million in 2050. Dementia refers to the decline of neuropsychological function, affecting one or more cognitive domains including memory, judgement, language, behavior, etc., whereby Alzheimer’s Disease (AD) is the most common type of dementia (Dubroff et al., 2015). Continued growth in the population of patients with AD will translate into an increasing economic burden. The World Alzheimer Report of 2015 indicates how the global costs of dementia have increased from US dollar 604 billion in 2010 to US dollar 818 billion in 2015 (Wimo et al., 2013). This financial burden affects patients, their family members and society (Dubroff et al., 2015). Despite the continued growth, it is estimated that only half of all cases are diagnosed due to the difficulty of recognizing first symptoms (Wimo et al., 2013 and Dubroff et al., 2015). Resulting in late application of therapy, which is currently limited to symptomatic relief. To deduce the previous mentioned impact, multiple stakeholders (clinicians, researchers, pharmaceutical companies, etc.) are asking party for tools that can help to provide an earlier and accurate clinical diagnosis. In this way, biological markers (biomarkers) are useful tools to identify the presence of a disease and to monitor disease progression better compared to the current diagnostic tools. From 2013 on, several Amyloid markers have been approved by, for example, the Food and Drug Administration (FDA) for clinical use. This approval has led researchers to the question whether or not the current policy of non-disclosure of individual research results in the research setting ought to be changed. However, several ethical questions occur: Is an early diagnosis always better? What are the pitfalls when using biomarkers in clinical and research setting? Does knowledge about your early diagnosis or test result always equal power?

In this PhD-project, our main focus is twofold: First of all, by mapping and clustering the ethical challenges in a clinical biomarker-based diagnosis of the early phase (MCI due to AD / pAD) of Alzheimer Disease. Secondly, by exploring and investigating the ethical challenges regarding the return of individual research result in the research context.

This project consists of 3 phases: In the first phase, a literature study about the current ethical literature on this topic. The second step consists of qualitative empirical research by conducting interviews with MCI patients as part of a clinical trial and focus group interviews with multiple stakeholders: researchers, clinicians, family members and so on. The third and concluding step upholds a normative ethical reflection.