Understanding treatment goals and their application in clinical trial design for patients with Alzheimer disease and caregivers.

Background: As research continues towards improved treatments for Alzheimer disease (AD), there is growing interest in the views and needs from patients and caregivers on AD treatments. Methods: In this study, we surveyed patients with AD and caregivers to determine the treatment goals that are most important to them. Patients with AD and caregivers were independently recruited in Europe and North America to complete a web-based survey. Eligible participants were ≥18 years old and diagnosed with mild cognitive impairment or mild-to-moderate AD (patient-reported group) or persons involved in the care of patients with AD (caregiver-reported group). A total of 322 patients and 614 caregivers completed the survey. Results: The demographic characteristics of patients in the patient-reported and the caregiver-reported groups were similar. Disease severity of patients was greater in the caregiver-reported group compared with the patient-reported group (72.1% versus 46.9% moderate AD). The most important goal of AD treatment in both groups was maintenance of quality of life (QoL) (patient-reported group 31.1% and caregiver-reported group 38.8%; p=0.01). This was consistent across disease stages or symptom severity except for patients with mild cognitive impairment in the caregiver-reported group where slowing the progression of memory loss was the most important treatment goal. Conclusions: Patient QoL was consistently the most relevant treatment goal for patients with AD and caregivers. In AD clinical trials, patient-relevant outcomes, for example, QoL, should be given high priority to reflect the needs and demands of patients with AD and their caregivers.A preliminary report of this work was presented at the 14th Clinical Trials on Alzheimer's Disease meeting (November 9-12, 2021).

Toward the optimized assessment of clinical outcomes in studies of novel treatments for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is characterized by a progressive decline in cognition and daily function, leading to a greater need for caregiver support. Clinical disease is segmented into a preclinical stage, mild cognitive impairment, and mild, moderate, and severe stages of Alzheimer's dementia. Although AD trials enroll participants at various stages of illness, treatment efficacy is often assessed using endpoints based on measures of outcomes that are held fixed across disease stages. We hypothesize that matching the primary outcomes measured in the endpoint hierarchy to the stage of disease targeted by the trial will increase the likelihood of detecting true treatment benefits. AREAS COVERED: We discuss current approaches to assessing clinical outcomes in AD trials, followed by a consideration of how effect detection can be improved by linking the stage of AD to the endpoints that most likely reflect stage-specific disease progression. EXPERT OPINION: Failing to account for stage-specific relevance and sensitivity of clinical outcomes may be one factor that contributes to trial failures in AD. Given the history of failure, experts have begun to scrutinize the relevance and sensitivity of outcomes as a potentially modifiable barrier to successful trials. To this end, we present a framework for refining trial endpoint selection and evaluation.