Competing designs for phase I clinical trials: a review.
Phase I clinical trials are typically small, uncontrolled studies designed to determine a maximum tolerated dose of a drug which will be used in further testing. Two divergent schools have developed in designing phase I clinical trials. The first defines the maximum tolerated dose as a statistic computed from data, and hence it is identified, rather than estimated. The second defines the maximum tolerated dose as a parameter of a monotonic dose-response curve, and hence is estimated. We review techniques from both philosophies. The goal is to present these methods in a single package, to compare them from philosophical and statistical grounds, to hopefully clear up some common misconceptions, and to make a few recommendations. This paper is not a review of simulation studies of these designs, nor does it present any new simulations comparing these designs.
Rosenberger
William F
WF
Department of Mathematics and Statistics, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Haines
Linda M
LM
D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020714:Maximum Tolerated Dose; D012107:Research Design; D013223:Statistics as Topic / Q000379:methods