Large Multicenter Trials: What Do They Achieve and What Should Be Done in Perfusion?

There have been a vast number of publications in the perfusion and cardiac surgical literature suggesting possible therapeutic benefits from many perfusion interventions. Most of the reports are case series and other observational studies; few are randomized trials, and most of these are small, focusing on surrogate endpoints. We know there are many factors that can affect outcome after cardiac surgery, and some of these can bias results of clinical studies. Evidence-based medicine has highlighted the importance of avoiding bias with good study design, critical appraisal, and careful application into clinical practice. Associations shown in observational studies do not provide reliable evidence of effect (causation). Random allocation to treatment groups accounts for many sources of bias, but small randomized trials can still be unreliable because they may identify a spurious positive finding by chance (type I error), as well as providing imprecise estimates of effect, as shown by wide confidence intervals. Obtaining data on actual outcomes with enough study power requires a large number of patients. Meta-analysis of small randomized trials can increase power, but this introduces other sources of bias. Large randomized pragmatic trials, using straightforward interventions reflecting routine clinical practice, can optimize the ability to generalize and therefore are clinically relevant and reliable. They thus provide the best evidence of effectiveness.