Designs for phase I clinical trials with multiple courses of subjects at different doses.
The goal of this article is to provide a new design framework and its corresponding estimation for phase I trials. Existing phase I designs assign each subject to one dose level based on responses from previous subjects. Yet it is possible that subjects with neither toxicity nor efficacy responses can be treated at higher dose levels, and their subsequent responses to higher doses will provide more information. In addition, for some trials, it might be possible to obtain multiple responses (repeated measures) from a subject at different dose levels. In this article, a nonparametric estimation method is developed for such studies. We also explore how the designs of multiple doses per subject can be implemented to improve design efficiency. The gain of efficiency from "single dose per subject" to "multiple doses per subject" is evaluated for several scenarios. Our numerical study shows that using "multiple doses per subject" and the proposed estimation method together increases the efficiency substantially.
Fan
Shenghua K
SK
Department of Statistics and Applied Probability, National University of Singapore, Singapore 117546, Singapore. kelly.fan@csueastbay.edu
Wang
You-Gan
YG
D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000517:prevention & control*; D020714:Maximum Tolerated Dose; D012107:Research Design; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors