APOE and Alzheimer disease: Hallmarks of poorly designed or conducted trials include failure of the placebo group to decline in the course of a trial (assuming an adequate observation period), failure to show separation of the placebo group from an active treatment arm such as donepezil, excessive measurement variability, or low levels of biological indicators of AD such as the percent of ApoE-4 carriers or the presence of fibrillar amyloid on amyloid imaging [22].