Neuroimaging outcomes for clinical trials

Abstract

A wide range of drugs is currently under development for treating Alzheimer's Disease (AD). Clinical trials traditionally use rating scales, such as neuropsychological tests and disability scales, as outcome measures. However, their intrinsic measurement variability, the slow disease progression, and the low effectiveness of the drugs developed so far have led to trial designs with hundreds of subjects per treatment arm. Furthermore, a key issue is to establish what effect are these compounds having on the biological progression of the disease, beyond delaying symptomatic progression. The development of imaging markers, either structural, functional, or amyloid, with proven sensitivity to disease progression has recently paved the way for their use as outcome measures in clinical trials. The use of imaging measures has the double advantage of decreasing the number of subjects per treatment arm whilst also providing a direct measure of the degree of disease modification induced by the "active" molecules. The reviewed techniques, except for the most recent amyloid imaging, are those applied to prospective studies investigating changes of imaging markers over time.