Keywords: Clinical Trial Design, Clinical Trial Simulations, ALS, historical controls, disease progression
There is a growing need to learn from our past in clinical trial design. In light of this, numerous efforts are being made to promote the creation of shared disease-specific databases with patient-level historical control and observational data. With these efforts in mind, we discuss how we can synthesize and make better use of historical information to design more informed and powerful clinical trials. One such use of historical disease-specific databases is to create realistic virtual patient simulation models to feed clinical trial simulations and better understand operating characteristics of potential future clinical designs. Throughout this presentation, we highlight the use of the shared Pooled Resource Open-Access ALS Clinical Trials Database (PRO-ACT) in designing a platform trial for amyotrophic lateral sclerosis (ALS). The PRO-ACT database provides patient-level longitudinal data from placebo and treatment arms from 23 Phase II/III clinical trials and is an exemplary effort to share data and learn from past studies. Access to rich patient-level data within the PRO-ACT database provides many advantages in designing the ALS platform trial, including informing the creation of realistic clinical trial simulations to optimize key design elements such as the primary endpoint and analysis method, key inclusion / exclusion criteria, sample size and length of follow-up.