Clinically meaningful outcomes in Alzheimer's disease and Alzheimer's disease related dementias trials.

UNLABELLED: On March 12-14, 2024, the National Institute on Aging (NIA) together with the National Institute of Neurological Disorders and Stroke (NINDS) led a workshop exploring clinically meaningful changes in the context of Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) clinical trials (https://www.nia.nih.gov/research/dbsr/workshops/clinically-meaningful-outcomes-ad-adrd-trials). The goals were to identify research gaps, opportunities, and tools to advance patient-centered, equitable assessment of clinically meaningful change focused on biomarker status, cognition, and everyday function. The workshop fostered robust, multidisciplinary discussion between lived experience experts, advocates, researchers, clinicians, funders, payers, and regulators. The workshop addressed the criteria used to assess whether an intervention has had a clinically meaningful impact, including consideration of both benefit and harm. Here, we report on (1) criteria to consider for development, testing, and selection of clinically meaningful outcomes in AD/ADRD clinical trials; (2) methods to validate and customize clinically meaningful outcomes that are fit-for-purpose; and (3) practices that will ensure that clinically meaningful outcomes are applicable to diverse populations.

HIGHLIGHTS: Patient-Centered Outcomes: Inclusive AD/ADRD clinical trials incorporate assessments that reflect what matters most to those impacted by these diseases, including patient- and caregiver-reported outcome measures. Culturally Relevant Assessments: There is a need for culturally sensitive and equitable assessments to better serve diverse populations in AD/ADRD research. Framework for Clinically Meaningful Change: We present a framework for defining and evaluating clinically meaningful outcomes in AD/ADRD trials, tailored to diverse stages of disease progression. Interdisciplinary Approach: We draw on insights from a multidisciplinary workshop, fostering collaboration among researchers, clinicians, and lived experience experts to advance the field.