Assessing the similarity of dose response and target doses in two non-overlapping subgroups

作者：Bretz Frank^*; Moellenhoff Kathrin; Dette Holger; Liu Wei; Trampisch Matthias

来源：Statistics in Medicine, 2018, 37(5): 722-738.

DOI：10.1002/sim.7546

• dose finding
• equivalence testing
• subgroup analysis
• target dose estimation

We consider 2 problems of increasing importance in clinical dose finding studies. First, we assess the similarity of 2 non-linear regression models for 2 non-overlapping subgroups of patients over a restricted covariate space. To this end, we derive a confidence interval for the maximum difference between the 2 given models. If this confidence interval excludes the pre-specified equivalence margin, similarity of dose response can be claimed. Second, we address the problem of demonstrating the similarity of 2 target doses for 2 non-overlapping subgroups, using again an approach based on a confidence interval. We illustrate the proposed methods with a real case study and investigate their operating characteristics (coverage probabilities, Type I error rates, power) via simulation.

• 出版日期2018-2-28