Development of a patient‐reported outcome measure for Alzheimer’s disease: the Alzheimer’s Disease‐Health Index (AD‐HI), a fully validated tool to bolster clinical trial and research infrastructure

Background As therapeutic advancements are made in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), it is important to have a fully validated, sensitive, and reliable disease‐specific patient‐reported outcome measure (PRO) to accurately measure changes in AD and MCI symptomatic disease burden. The U.S. Food and Drug Administration has encouraged the use of PROs to measure therapeutic benefit of potential new treatments. This research describes the development, testing, and validation of a novel, multifactorial PRO: The Alzheimer’s Disease‐Health Index (AD‐HI). Methods We conducted interviews and a large cross‐sectional study involving individuals with AD and MCI and their caregivers to determine what symptoms and issues are most important to patients (Figure 1). Questions were selected for the AD‐HI based on their importance to patients with MCI and AD, potential to respond to therapeutic intervention, and generalizability to the broader MCI and AD patient population as determined through qualitative interviews and a cross‐sectional study. We beta tested the initial version of the AD‐HI with individuals with MCI and AD to determine its clarity, ease of use, and relevance to those with MCI and AD. We performed test‐retest reliability, known groups validity, internal consistency, and area under the curve analyses of the AD‐HI to assess the statistical characteristics, performance, and clinical meaningfulness of the outcome measure. Results The content of the AD‐HI was validated using a cross‐sectional study of 104 patients. The final version of the AD‐HI contains 9 subscales that measure disease burden in the following areas: 1) Memory, 2) Cognitive health, 3) Fatigue, 4) Sleep, 5) Social health, 6) Communication, 7) Emotional health, 8) Physical health, and 9) Pain. The AD‐HI was identified as easy to use, relevant to the patient population, responsive, and clear during beta testing. The ADCR‐HI was shown to be reliable during test‐retest reliability testing with 22 individuals and able to distinguish between patient cohorts with different disease severities. Conclusion The AD‐HI is a is a valid, sensitive, and reliable marker of disease burden in AD This disease‐specific outcome measure is available for use by researchers, clinicians, patient organizations, and companies to measure changes in disease burden during therapeutic trials.