The clinical research enterprise in critical care: What's right, what's wrong, and what's ahead?

Intensivists have been remarkably successful in using randomized controlled trials to assess aspects of current practice. Unfortunately, this success has not been mirrored in trials of new pharmacotherapy, despite convincing pathophysiological ration-ales and encouraging preliminary studies. Misunderstandings of biological processes and flawed early clinical studies have led to the almost universal failure of fundamentally new treatments subjected to large phase III trials, despite their sound methodology. Compounding these problems is the tendency for new approaches to be either implemented widely on the basis of relatively poor studies or ignored despite strong supporting evidence. Having mastered the principles of evidence-based medicine in assessing existing therapy, intensivists have established a strong foundation. Critical care medicine must now embrace the challenge of translating a more solid understanding of basic disease mechanisms into widely implemented treatments. (Crit Care Med 2009; 37[Suppl.]:S1-S9)