BACKGROUND: Recent guidance from the US Food and Drug Administration (FDA) indicates that measures of treatment effect in early Alzheimer’s disease (AD) must be clinically meaningful (FDA, 2018; Edgar et al., 2019). Researchers have taken different approaches to eliciting what matters to individuals with or at risk for AD and their caregivers. Such approaches include reviewing existing instruments to develop conceptual models of patient-relevant concepts (e.g., Hartry et al., 2018); conducting qualitative interviews and instrument reviews to develop composite measures of patient-relevant changes in early AD (e.g., Ropacki et al., 2017; Gordon et al., 2016); and developing instruments to measure progression from normal aging to dementia (Jutten et al., 2017). The Alzheimer’s Disease Patient and Caregiver Engagement (AD PACE) What Matters Most (WMM) study is a two-part study designed to better understand and assess treatment-related needs, preferences, and priorities among individuals with or at risk for AD and their care partners. Phase 1 involved in-depth interviews with 60 individuals and care partners (12 individuals with unimpaired cognition but evidence of AD pathology, 12 with mild cognitive impairment and evidence of AD pathology, 12 with mild AD, 12 dyads of individuals with moderate AD and their care partners, and 12 care partners of individuals with severe AD) to elicit symptoms and behaviors that matter most to patients and care partners across the continuum of AD (Vradenberg et al., 2019). Phase 2 will quantitatively estimate how much each potential treatment related outcome matters and which potential outcomes matter most to these populations.
OBJECTIVES: Compare WMM qualitative results and existing literature to develop a list of symptoms and behaviors important to people with and at risk for AD and care partners to inform the WMM quantitative study.
METHODS: Concepts from the WMM interviews and relevant literature were compiled. Redundancies were removed, resulting in a list of 83 potential concepts of interest (COI). Reduction of this list involved deleting redundancies, dividing “double-barreled” concepts into simpler concepts and streamlining remaining concepts. Further reduction and revisions were based on consensus of two researchers who conducted the WMM interviews and reviewed by a third researcher not involved in the WMM interviews, resulting in a total of 57 concepts. Through further iterative rounds of review and streamlining, 45 concepts were identified as sufficiently distinct and items were developed for each. Items were pretested in in-person interviews with 8 patients and 7 care partners prior to WMM Phase 2.
RESULTS: During pretesting, 4 items were removed, 2 items were combined, and 2 new items were developed. The final set comprised 42 items.
CONCLUSION: Recent work in this area has primarily focused on identifying concepts that are relevant to people with early signs of cognitive impairment or mild AD. The concepts identified in the WMM study can be used to measure what matters most to patients and care partners across the entire continuum of AD and eventually inform the development of an AD-specific instrument. Having a standard set of AD COIs will provide a potentially important tool to assure that current and future clinical outcome assessments measure changes that matter most to patients and care partners across the lived experience with AD.
