Protecting participants of clinical trials conducted in the intensive care unit.

Research in the intensive care unit (ICU) raises a number of scientific and ethical challenges. Potential participants in critical care studies are likely to be considered particularly vulnerable-they may lack sufficient capacity to make informed decisions about trial participation, their health care proxies may lack legal authority to enroll them in research trials or may not know their true intent, and the life-threatening nature of the illness may make them or their surrogates more susceptible to therapeutic misconception. Because of this, critical care investigators must exercise extreme caution when designing and conducting studies in the ICU. In this article, we review the key literature addressing the various scientific and ethical issues raised by critical care research, including questions of equipoise and the selection of control groups, informed consent, therapeutic misconception, conflict of interest, and quality improvement projects. We also describe the current status of key policy or regulatory initiatives designed to address these issues, particularly in light of recent controversies involving critical care studies like the ARDSNet trial.