Background: Drug development for Alzheimer’s disease (AD) is increasingly expensive and time-consuming. To decrease the high failure rate of these trials, it will be necessary to improve clinical trial design by reducing total trial size and/or recruitment time. Randomized controlled trials (RCTs) have long been the gold-standard among clinical trial designs, even though they can be very inefficient. The volume of clinical trials provides an opportunity to improve the efficiency of AD trials, which has been highlighted by the FDA in a number of communications. With data collected from the control groups of many prior AD trials and state-of-the-art statistical methods, we have developed machine learning (ML) technology to comprehensively model the progression of control subjects. Our model can generate digital twins, which are digital subject records generated from the baseline data of actual subjects in a trial. These digital twins show the potential outcomes of individual subjects had they received a placebo.