Why Has a Run-In Period Been a Design Element in Most Landmark Clinical Trials? Analysis of the Critical Role of Run-In Periods in Drug Development

Prior exposure to one of the randomized treatments has been a routine design element of large-scale trials in patients at high cardiovascular risk. A run-in feature has allowed our trials to be more realistic; it has strengthened their ability to estimate the true treatment effect; and it has never undermined the validity of a trial's findings. Those who suggest that run-in periods distort the results of large-scale trials should become more familiar with our history of drug development and our standards of clinical practice. Physicians use run-in periods every day in real life, and trialists have used run-in periods for decades to reliably establish the role of new cardiovascular drugs. Those who reflexively criticize the trials because of their inclusion of a run-in period need to carefully reexamine how medicine is practiced and how it advances.