Monitoring of clinical trials: Interim monitoring, data monitoring committees, and group sequential methods

Introduction The aging population is increasing the global burden of neurological diseases and the need for safe and effective therapeutics for these disorders. While therapeutic targets for neurological disorders are increasingly tractable, neurology also has one of the highest failure rates in late stage clinical trials. There is an increasing need for proficiency in the design, conduct, analysis, and interpretation of clinical trials in neurology. This is especially true in the early and middle stages of therapeutic development, which determine if and how comparative efficacy studies should be conducted. The goal of this book is to describe how the principles of clinical trials can be applied to the challenges that arise in developing therapies for neurological disorders. The fundamentals of clinical trials are explored in several existing texts and are the same across different fields of medicine. Here we describe the application of those principles to the specific clinical questions that arise with the study of neurological diseases. There is no one trial design that meets all objectives for a particular phase of development. Rather there are parameters that need to be optimized for each intervention, question, and study. A clinical trial can be defined as an experiment in humans that is designed to test a medical, surgical, behavioral, or other type of intervention. This definition does not presuppose a particular design, type of control group, or analysis plan. When designing a trial and consulting this text for guidance, the reader should carefully consider the clinical question they are facing and how that question fits in the overall program of research for the intervention. The next step is to select a design that can practically and efficiently answer the question and guide decision-making about the intervention and the steps to further develop it.