Adaptive designs in clinical trials in critically ill patients: principles, advantages and pitfalls

Excerpt

Randomised controlled trials (RCTs) are the gold standard for a comparative evaluation of interventions. Their robust design helps prevent different biases, most importantly confounding by indication. However, RCTs often require large numbers of patients, and even then many appear to be underpowered—and thus inconclusive—due to misspecification of original assumptions used for sample size calculation [1, 2]. Furthermore, especially in critically ill patients, it is difficult to acquire informed consent for interventions that need to start immediately, such as treatment of infections. This may result in selected populations, reducing the generalisability of study findings [3]. Adaptive trials are trials that include decision rules to change key trial design elements during the RCT. The promise of adaptive trials is to provide answers to therapeutic research questions as efficiently as possible without compromising reliability. They can be designed such that a conclusive answer is always reached and that—during the course of the study—the proportion of patients receiving the most promising treatment increases [4]. This benefit for individual patients may overcome ethical barriers to apply deferred or waived consent for randomisation, and thereby increase generalisability of the results. In this viewpoint we aim to elucidate principles, advantages and pitfalls of adaptive trials. …