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Keywords: Bayesian adaptive, continual reassessment method (CRM), first time in human, maximum tolerated dose (MTD), single-ascending dose, non-oncology
Bayesian adaptive dose-finding designs have been popular within the oncology clinical trials literature for almost two decades. However, these designs are not commonly used in other therapeutic areas. In this presentation, the current literature regarding the use of Bayesian designs outside of oncology in first time in human (FTIH) studies will be discussed. In addition, the benefits of applying a Bayesian continual reassessment method (CRM) to determine the maximum tolerated dose (MTD) in a single ascending dose study versus a more traditional approach will be assessed. The new approach implementing a Bayesian adaptive design shows key advantages including a more precise estimation of the MTD, as well as a reduction in both the total number of healthy subjects used in the trial and the number of subjects who are exposed to doses in excess of the true MTD in addition to the ability to detect intermediary doses that may not be part of the originally planned dose schedule. An example from an actual FTIH single-ascending dose study in the neurology therapeutic area will illustrate these important properties along with a proposal for implementation in future studies.