Operationalizing selection criteria for clinical trials in Alzheimer's disease: Biomarker and clinical considerations: Proceedings from the Alzheimer's Association Research Roundtable (AARR) Fall 2021 meeting.

UNLABELLED: The design of clinical trials in Alzheimer's disease (AD) must consider the development of new plasma, cerebrospinal fluid (CSF), and imaging biomarkers. They must also define clinically meaningful outcomes for patients and set endpoints that measure these outcomes accurately. With the accelerated United States Food and Drug Administration (FDA) approval of the first anti-amyloid, disease-modifying treatment for AD, a monoclonal antibody called aducanumab, the landscape of clinical trial design is evolving. Enrolment in clinical trials may be impacted by the availability of this and other treatments, and trial design must take into consideration that patients may desire a disease-modifying treatment rather than potentially being randomized to the placebo arm. The Alzheimer's Association Research Roundtable (AARR) Fall 2021 meeting discussed the consideration of well-defined AD staging criteria in protocol design and how they influence more standardized inclusion/exclusion criteria for trials, as well as what constitutes meaningful differentiation between the stages. Discussion explored the current state of knowledge regarding biomarkers and how they can inform AD staging criteria, as many trials are now designed based on specific biomarker features, further underscoring the importance of coordinating AD staging criteria and biomarkers. The relationship between cognition and biomarkers has been studied and this must continue as trials move forward. Researchers, patients, clinicians, regulatory scientists, and payers discussed the state of the field as well as the future of symptomatic Alzheimer's disease clinical trials.

HIGHLIGHTS: The Alzheimer's Association Research Roundtable (AARR) convened leaders from academia and industry as well as patients, care partners, clinicians, regulators, and payers to discuss the topic of operationalizing selection criteria for clinical trials and the role of biomarkers.Well-defined Alzheimer's disease (AD) staging criteria are an important consideration in study protocol design.Staging criteria and biomarkers must be coordinated to yield high-quality clinical trial results that have meaning for patients with AD by selecting a population most likely to benefit from a specific treatment.