Florian, Hana

Abstract 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.

Abstract Alzheimer's disease (AD) staging criteria lack standardized, empirical description. Well‐defined AD staging criteria are an important consideration in protocol design, influencing a more standardized inclusion/exclusion criteria and defining what constitutes meaningful differentiation among the stages. However, many trials are being designed on the basis of biomarker features and the two need to be coordinated. The Alzheimer's Association Research Roundtable (AARR) Spring 2021 meeting discussed the implementation of preclinical AD staging criteria, and provided recommendations for how they may best be incorporated into clinical trials research. Discussion also included what currently available tools for global clinical trials may best define populations in preclinical AD trials, and if are we able to differentiate preclinical from clinical stages of the disease. Well‐defined AD staging criteria are key to improving early detection, diagnostics, clinical trial enrollment, and identifying statistically significant clinical changes, and researchers discussed how emerging blood biomarkers may help with more efficient screening in preclinical stages.