Utility-Based Dose-Finding in Practice: Some Empirical Contributions and Recommendations

Abstract

selection. The selection of doses (number and spacing) is also discussed in terms of sensitivity of the framework to such aspects; the properties of the operating characteristics in this respect are explored. On the other hand, we assess, through simulations, the influence of phase II sample size, based on the relative utility loss criterion, and we compare different (fixed, adaptive) designs based on the suggested stopping criteria for interim analysis. This section is complemented by an analysis example based on a real dose-find ing study. Finally, the Discussion and Conclusions section consists in summarizing our decision-making framework (decision rules for dose selection, and decision criteria for phase II recommendations and interim analysis). Abstract Aspects related to dose-finding trials are of major importance in clinical development. Poor dose selection has been recognized as a key driver of failures in late phase development programs and postponements in drug approvals. The aim of this paper is to develop a flexible utility-based dose selection framework for phase II dose-finding studies that has satisfactory operating characteristics. This framework also allows to plan interim analyses with stopping rules that can be easily defined and interpreted by the clinical team within this same framework.