On weighted composite scores for early Alzheimer's trials

Recent research on finding appropriate composite endpoints for preclinical Alzheimer's disease has focused considerable effort on finding "optimized" weights in the construction of a weighted composite score. In this paper, several proposed methods are reviewed. Our results indicate no evidence that these methods will increase the power of the test statistics, and some of these weights will introduce biases to the study. Our recommendation is to focus on identifying more sensitive items from clinical practice and appropriate statistical analyses of a large Alzheimer's data set. Once a set of items has been selected, there is no evidence that adding weights will generate more sensitive composite endpoints.