The EPAD (European Prevention of Alzheimer’s Dementia) and DIAN (Dominantly Inherited Alzheimer’s Network) consortiums incorporate innovation in disease progression modeling, leveraging of natural history data, and Bayesian adaptive trial designs. These innovations quickly, efficiently, and ethically identify effective treatments; however, these large-scale initiatives require close collaboration and buy-in from both clinicians and statisticians. In addition to discussing the innovative features in EPAD and DIAN, we will focus on the collaborative process required to design these trials, discussing points of contention among the many parties involved in the design process and how these points were resolved to produce the final trial design. These issues include reticence about incorporating new ideas with limited examples of previous trials (“we will accept any new idea, as long as it has been tried before!”) and providing assurance about regulatory acceptance. Through technical leadership, scientific innovation, and thoughtful collaboration, statisticians can uniquely translate these new ideas into effective clinical trials.