Efficacy and effectiveness trials have different goals, use different tools, and generate different messages

Abstract

The discussion about the optimal design of clinical trials reflects the perspectives of theory-based scientists and practice-based clinicians. Scientists compare the theory with published results. They observe a continuum from explanatory to pragmatic trials. Clinicians compare the problem they want to solve by completing a clinical trial with the results they can read in the literature. They observe a mixture of what they want and what they get. None of them can solve the problem without the support of the other. Here, we summarize the results of discussions with scientists and clinicians. All participants were interested to understand and analyze the arguments of the other side. As a result of this process, we conclude that scientists tell what they see, a continuum from clear explanatory to clear pragmatic trials. Clinicians tell what they want to see, a clear explanatory trial to describe the expected effects under ideal study conditions and a clear pragmatic trial to describe the observed effects under real-world conditions. Following this discussion, the solution was not too difficult. When we accept what we see, we will not get what we want. If we discuss a necessary change of management, we will end up with the conclusion that two types of studies are necessary to demonstrate efficacy and effectiveness. Efficacy can be demonstrated in an explanatory, ie, a randomized controlled trial (RCT) completed under ideal study conditions. Effectiveness can be demonstrated in an observational, ie, a pragmatic controlled trial (PCT) completed under real-world conditions. It is impossible to design a trial which can detect efficacy and effectiveness simultaneously. The RCTs describe what we may expect in health care, while the PCTs describe what we really observe.