Should recent insights into placebo and nocebo mechanisms force a change in clinical trial design and therapeutic setting?

During this workshop we will review recent evidence regarding the neurobiology underlying placebo and nocebo hyperalgesia and discuss the potentially far reaching implications for medical practice and clinical trial design. First, we will present the data from neuroimaging studies and from experimental and clinical pain experiments revealing the neurobiology underlying placebo and nocebo phenomena. Studies suggest that multiple brain regions combined with peripheral physiology changes may play a pivotal role in these processes. However, there continues to be much debate as to which areas consistently contribute to these networks. This uncertainty and the difference in the results obtained will be critically discussed. Second, we will address how these findings can be applied to the clinical setting, in general, and to a more personalized form of treatment taking into account individual differences in placebo/nocebo responsiveness to optimize the overall outcome. Recent data on the impact of psychosocial factors (i.e. expectancy, conditioning) on active pharmacological treatments will also be presented. Finally, we will address placebo and nocebo phenomena in the context of clinical trials. In particular, adequate methodology is a critical issue in the planning and execution of randomized controlled clinical trials, as different methodological approaches can result in different conclusions. We will discuss how our current knowledge regarding the psychological and neurobiological components of placebo and nocebo responses should force us to reconsider the design of clinical trials. Importantly, the results of this analysis will help us to hypothesize significant changes to clinical trial design and therapeutic setting.