In this article (the first of a two-part interview), Benjamin Djulbegovic, MD, PhD, discusses the uncertainty principle in clinical trials, a subject he has written about in The Lancet and elsewhere. Dr. Djulbegovic is associate professor of medicine, Divisions of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa.
Oncology News International: What is uncertainty?
Dr. Djulbegovic: Uncertainty is inherent in clinical medicine, although many physicians are unwilling to recognize it. It is this need for certainty that leads to excessive diagnostic testing and inappropriate treatments, which result in ballooning health care costs. Uncertainty can have many grades. It can range from complete ignorance to simply not knowing, say, about the relative benefits and harms of the treatment alternatives.
Our relationship toward uncertainty is an epistemological problem. For example, the uncertainty that we are discussing hereexperimental testing within the context of clinical trialsis defined by our previous knowledge (and the quality of that knowledge) such as the existence of available evidence, experience, and biological plausibility about a given treatment. Ludmerer has recently made a compelling case that the failure to train clinicians properly for clinical uncertainty was the greatest deficiency of medical education throughout the 20th century.
ONI: What are the tools used to resolve these uncertainties?
Dr. Djulbegovic: In general, we can deal with uncertainty in several ways, all of which will fundamentally depend on our preexisting knowledge about the value of the treatments to be compared.
In some cases, preexisting knowledge can be accurate, based solely on the experience and inferences of individual practitioners, as, for example, the use of penicillin in the treatment of pneumococcal infections. Reliance on physician experience may also lead to false resolution of the uncertainty, however, such as the 200-year practice of venesection for treatment of bacterial infections.