Multiple Comparison Methods in Zero-dose Control Trials

• Published in: Journal of Data Science Vol. 16; no. 2; pp. 299 - 326
• Main Authors: Zyl, Johanna S. van, Tubbs, Jack D.
• Format: Journal Article
• Language: English
• Published: 中華資料採礦協會 24.02.2021
• Subjects: minimum effective dose; Jonckheere-Terpstra trend test; closed test; family-wise error rate; AUC regression
• ISSN: 1683-8602; 1680-743X; 1683-8602
• DOI: 10.6339/JDS.201804_16(2).0005

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 methods 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 multiple comparison procedures. The method is further illustrated using a problem from a clinical setting.