Benefit:Risk Assessments During Clinical Trials: A Prediction Approach Using the Desirability of Outcome Ranking (DOOR)

We discuss issues and points to consider in the evaluation of benefit:risk during interim monitoring in clinical trials. We describe the use of the Desirability of Outcome Ranking (DOOR) methodology with the prediction approach for monitoring a clinical trial to minimize the harms and inconvenience to trial participants and to maximize the potential benefits, and to determine that the benefit:risk profile is acceptable. The DOOR is a paradigm for the design, analysis, interpretation and reporting of clinical trials and other research studies based on patient-centric benefit:risk evaluation. The prediction approach is a flexible monitoring tool for clinical trials using predicted intervals, a prediction of the confidence intervals for a parameter of interest at some future time point such as the end of a trial. We also describe prediction visualizations to make complex scenarios more accessible, understandable, and usable. We illustrate the method with an example.