Nonparametric Stepwise Procedure for Identification of Maximum Safe Dose (MSD)
Michael J. Adjabui *
Department of Mathematics, University for Development Studies, Navrongo Campus, Ghana.
Nathaniel K. Howard
Department of Mathematics and Statistics, University of Cape Coast, Ghana.
Albert Luguterah
Department of Statistics, University for Development Studies, Navrongo Campus, Ghana.
*Author to whom correspondence should be addressed.
Abstract
In this article we consider identification of maximum safe dose (MSD) in a dose response study for distribution-free endpoints. Where the maximum safe dose is the highest dose level that does not exceed the median toxicity of the zero dose by a predetermined margin. A nonparametric confidence set-based approach was proposed, that is we incorporate Mann-Whitney method with the partitioning principle in a step-down fashion for safety evaluation. A comprehensive study of the familywise error rate for our new procedure was compared with the dose response (DR) procedure via a Monte Carlo simulations. An example from preclinical trial in genetic toxicology was used for illustrative purpose.
Keywords: Maximum safe dose, partitioning principle, distribution-free endpoint, familywise error rate, confidence set.