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One-sided Simultaneous Confidence Intervals for Effective Dose Steps in Unbalanced Designs

✍ Scribed by Ludwig A. Hothorn; Frank Bretz


Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
108 KB
Volume
42
Category
Article
ISSN
0323-3847

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✦ Synopsis


An important issue in dose finding is whether a further dose increment leads to a relevant increase in efficacy. Clinical efficacy should not be considered by point zero null hypotheses. Instead, shifted hypotheses for the difference or the ratio can be used. Because the a priori definition of a relevance threshold is frequently difficult, confidence intervals should be used for a posteriori interpretation. Sample size estimationa-priori or by adaptive interim analysis-is inherent, because the effective dose steps are arbitrary in un-designed studies.

For simultaneous confidence intervals without order restriction the exact distributions under the null and the alternative hypothesis is proposed for the general unbalanced one-way design.