The i3+3 design for phase I clinical trials.

Phase I clinical trials

Phase I trials are conducted to find a dose to use in subsequent trials. They provide data on the rate of adverse events at different dose levels and provide data for studying the pharmacokinetics and pharmacology of the drug. Dose-finding studies that involve therapies with little or no toxicity often enroll healthy volunteers and usually have a control group. Trials in oncology and other life...

Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

BACKGROUND More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the op...

Phase I Clinical Trial Design

Design of Phase III Clinical Trials

Design considerations for dose-expansion cohorts in phase I trials.

Phase I trials are increasingly including dose-expansion cohorts after the maximum-tolerated dose (MTD) has been reached to better characterize the toxicity profile or identify early signs of efficacy within a specific disease population. This article provides guidelines on how to monitor safety and re-evaluate the MTD using data obtained from expansion cohorts of phase I protocols. We illustra...