Understanding burden of proof and equipoise in the design of pragmatic clinical trials: An example from a trial on brain arteriovenous malformations.

BACKGROUND AND PURPOSE: The burden of proof principle is rarely discussed and poorly understood, but central to the proper design of pragmatic clinical trials. A better understanding of the principle could play an important role in the re-introduction of scientific methods within practice and in revising fundamental problems with the current research-care separation.

METHODS: We analyze the design of the ARUBA trial on the management of unruptured brain arteriovenous malformations. We also review how the concept of clinical equipoise was introduced to address a misconceived problem of research ethics.

RESULTS: The ARUBA trial hypothesis in favour of conservative management of brain arteriovenous malformations failed to take into account the fact that the burden of proof was on surgery, endovascular treatment or radiation therapy. Thus, results remained inconclusive and other trials are needed. The equipoise notion fails to take into account that the burden of proof is on unvalidated medical or surgical interventions, if we want to provide outcome-based medical care that patients can trust.

CONCLUSION: The burden of proof principle is essential to properly design pragmatic trials. This principle also explains why in certain circumstances optimal care is a randomized care trial.