Chapter 1 Randomized Controlled Trials: Methodology, Outcomes, and Interpretation

Abstract

Randomized clinical trials (RCTs) have become the gold standard against which other clinical research is compared because of their ability to demonstrate clinically meaningful differences between interventions despite the biologic noise inevitable in human experimentation. Although the RCT is the clinical research design most closely resembles the tightly controlled experiment in the basic science laboratory, the complexity of experimenting on genetically and environmentally unique humans creates special challenges and necessitates extra care in research design and execution to avoid common and potentially disastrous pitfalls. This chapter provides an overview of the major issues in RCT design, implementation, and interpretation using examples from clinical trials in neurologic diseases when possible. The chapter provides a practical guide for reading and applying RCT data in daily practice. There are three critical components of a clinical trial: (1) the prospective nature of data collection, (2) the introduction of an intervention, and (3) the comparison of patients receiving the intervention to prospectively followed patients who do not receive the intervention. The prospective nature of data collection separates a clinical trial from a case-control or retrospective cohort study. The presence of an intervention distinguishes a clinical trial from a prospective cohort study. The presence of a control group delineates a clinical trial from a case series. Although all of these other types of studies are aptly termed “clinical research,” they are not clinical trials.