Assessment of outcome in clinical trials in mild Alzheimer’s disease: Urgent time for a rethink?

Abstract

Introduction: A major barrier for clinical trials in Alzheimer's disease is the lack of sensitive clinical endpoints for the early stages. Until recently, regulatory agencies have required demonstration of improvement in two disease domains, cognition plus functional or global status, as the evidence of symptomatic improvement during clinical trials for Alzheimer's disease. However, the model of Alzheimer's disease progression indicates impairment in cognition occurs earlier than changes in function and new draft guidance from the Food and Drug Administration considers change in cognition as an endpoint. The aim of this paper is to assess the outcomes of clinical trials in mild Alzheimer's disease. Short communication: The Alzheimer's disease assessment scale - cognitive subscale is the most widely used assessment of cognition in clinical trials; however, analysis of its psychometric properties, show it lacks the sensitivity to detect change in cognition in mild Alzheimer's disease. There is a need to develop a new outcome measure capable of capturing the subtle changes associated with mild AD in a reliable and valid way. Conclusion: Given the heterogeneity of AD phenotypes, development of a reliable, valid and clinically meaningful outcome measure is complex and challenging and will require discussion and cooperation between researchers, clinicians, industry and patients and their advocates to achieve success.