Strategies to disrupt the biology of Alzheimer’s Disease (AD) with disease-modifying agents fundamentally impact many aspects of trial design for AD. Industry is actively pursuing trial designs targeting patients in stages preceding AD where intervention could have the biggest biological impact. Successful early trials will require newer methodologies to capture subtle changes in early disease states. This session explores methodological issues in the design of prevention and prodromal AD trials, including developing sensitive outcome measures for early disease states; methods to reduce variability; and the challenges and potential utility of biomarkers at various stages of the trial, including endpoints. We bring together an expert group of panelists, both clinicians and statisticians, from the FDA, industry and academia, to discuss these issues and provide regulatory perspectives. The format of the session will be a panel discussion with pre-selected topics. Audience members will also have an opportunity to ask questions.