In this issue of JAMA, Fan et al1 review the treatment of acute respiratory distress syndrome (ARDS), focusing on recent randomized clinical trials (RCTs). Most of these RCTs failed to show that the interventions that were tested offered significant benefit. These predominantly negative results may prompt the question of whether other rational and more-effective ways are available to increase knowledge and improve treatment of a syndrome that is common, deadly, and arguably emblematic of modern intensive care. Although many of these trials were admirably executed, their failure to demonstrate benefit may often have been due to uncertainties regarding enrollment criteria and imprecise deployment of the interventions that were being tested.