Evolution not revolution: the future of the randomised controlled trial in intensive care research

Abstract

Over the past two decades, hundreds of parallel arm, double blind and open label randomised trials have been conducted in the critically ill. The Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group (CTG) has been at the forefront, conducting pivotal trials that have changed international practice in fields such as fluid resuscitation,1,2 sepsis,3,4 renal failure,5 traumatic brain injury6 and nutrition7. To date, only a handful of multicentre randomised trials have demonstrated improved patient outcomes.8,9 The initial promise of interventions such as protocolised, goaldirected haemodynamic resuscitation for early septic shock (early goaldirected therapy),3,10 tight glycaemic control11,12 and recombinant human activated protein C for severe sepsis13 has not been reproduced in subsequent confirmatory trials. Subsequent debate over the role of randomised trials to inform intensive care practice has led to calls for them to be abandoned,14 with others stating that they are “doomed to fail”.15 Is such a revolution in research methodology required? Or is it possible for the randomised clinical trial to evolve? A summary of studies discussed in this article is provided in the Box.