Abstract
In this paper, the problem of determining which treatments are statistically significant when compared with a zero-dose or placebo control in a dose-response study is considered. Nonparametric meth- ods developed for the commonly used multiple comparison problem whenever the Jonckheere trend test (JT) is appropriate is extended to the multiple comparisons to control problem. We present four closed testing methods, of which two use an AUC regression model approach for determining the treatment arms that are statistically different from the zero-dose control. A simulation study is performed to compare the proposed methods with two existing rank-based nonparametric mul- tiple comparison procedures. The method is further illustrated using a problem from a clinical setting.
Highlights
Multiple comparison methods are used to determine individual group dif- ferences once a global test indicates overall group differences
A method for using the Jonckheere trend test statistic as applied in the area under the ROC (AUC) regression set- ting is presented in Buros et al (2017b)
A related problem is to determine the smallest dose for which there is a significant difference from the zero-dose control.This dose is referred to as the Minimum Effective Dose (MED) Ruberg (1989)
Summary
Multiple comparison methods are used to determine individual group dif- ferences once a global test indicates overall group differences. A method for using the Jonckheere trend test statistic as applied in the AUC regression set- ting is presented in Buros et al (2017b). Their method is extended to a problem associated with dose-response clinical studies for which one is interested in determining which dose arms are statistically different from a zero-dose or placebo control. A related problem is to determine the smallest dose for which there is a significant difference from the zero-dose control.This dose is referred to as the Minimum Effective Dose (MED) Ruberg (1989). The literature has several parametric (Dunnett (1955), 300 Multiple Comparison Methods in Zero-dose Control Trials. Procedures for identifying the MED are based on multiple contrast methods Ruberg (1989) or stepwise procedures described in Jan and Shieh (2004) and Tamhane et al (1996)
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