Designing Dose-Finding Phase I Clinical Trials: Top 10 Questions That Should Be Discussed With Your Statistician.

Abstract

In recent years, the landscape in clinical trial development has changed to involve many molecularly targeted agents, immunotherapies, or radiotherapy, as a single agent or in combination. Given their different mechanisms of action and lengths of administration, these agents have different toxicity profiles, which has resulted in numerous challenges when applying traditional designs such as the 3 + 3 design in dose-finding clinical trials. Novel methods have been proposed to address these design challenges such as combinations of therapies or late-onset toxicities. However, their design and implementation require close collaboration between clinicians and statisticians to ensure that the appropriate design is selected to address the aims of the study and that the design assumptions are pertinent to the study drug. The goal of this paper is to provide guidelines for appropriate questions that should be considered early in the design stage to facilitate the interactions between clinical and statistical teams and to improve the design of dose-finding clinical trials for novel anticancer agents.