Introduction: New treatments for neurodegenerative disease are urgently needed, and clinical trial methods are an essential component of new drug development. Although a parallel-group study design for neurological disorder clinical trials is commonly used to test the effectiveness of a new treatment as compared to placebo, it does not efficiently use information from the on-going study to increase the success rate of a trial or to stop a trial earlier when the new treatment is indeed ineffective.
Methods: We review some recent advances in designs for clinical trials, including futility designs and adaptive designs.
Results: Futility designs and noninferiority designs are used to test the nonsuperiority and the noninferiority of a new treatment, respectively. We provide some guidance on using these two designs and analyzing data from these studies properly. Adaptive designs are increasingly used in clinical trials to improve the flexibility and efficiency of trials with the potential to reduce resources, time, and costs. We review some typical adaptive designs and new statistical methods to handle the statistical challenges from adaptive designs.
Discussion: Statistical advances in clinical trial designs may be helpful to shorten study length and benefit more patients being treated with a better treatment during the discovery of new therapies for neurological disorders. Advancing statistical underpinnings of neuroscience research is a critical aspect of the core activities supported by the Center of Biomedical Research Excellence award supporting the Center for Neurodegeneration and Translational Neuroscience.
Keywords: Adaptive designs; Clinical trials; Futility design; Neurological disorders; Proper statistical inference.