Dose finding for continuous and ordinal outcomes with a monotone objective function: a unified approach.
In many phase I trials, the design goal is to find the dose associated with a certain target toxicity rate. In some trials, the goal can be to find the dose with a certain weighted sum of rates of various toxicity grades. For others, the goal is to find the dose with a certain mean value of a continuous response. In this article, we describe a dose-finding design that can be used in any of the dose-finding trials described above, trials where the target dose is defined as the dose at which a certain monotone function of the dose is a prespecified value. At each step of the proposed design, the normalized difference between the current dose and the target is computed. If that difference is close to zero, the dose is repeated. Otherwise, the dose is increased or decreased, depending on the sign of the difference.
Ivanova
Anastasia
A
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7420, USA. aivanova@bios.unc.edu
Kim
Se Hee
SH
D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008962:Models, Theoretical; D012107:Research Design; D016896:Treatment Outcome