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Three-arm `gold-standard' non-inferiority trials are recommended forindications where only unstable reference treatments are available and the useof a placebo group can be justified ethically. For such trials several studydesigns have been suggested that use the placebo group for testing 'assaysensitivity', i.e. the ability of the trial to replicate efficacy. Should thereference fail in the given trial, then non-inferiority could also be shownwith an ineffective experimental treatment and hence becomes useless. In thispaper we extend the so called Koch-R\"ohmel design where a proof of efficacyfor the experimental treatment is required in order to qualify thenon-inferiority test. While efficacy of the experimental treatment is anindication for assay sensitivity, it does not guarantee that the reference issufficient efficient to let the non-inferiority claim be meaningful. It hastherefore been suggested to adaptively test non-inferiority only if thereference demonstrates superiority to placebo and otherwise to test$\delta$-superiority of the experimental treatment over placebo, where $\delta$is chosen in such a way that it provides proof of non-inferiority with regardto the reference's historical effect. In this paper we extend the previous workby complementing its adaptive test with compatible simultaneous confidenceintervals. Confidence intervals are commonly used and suggested by regulatoryguidelines for non-inferiority trials. We show how to adopt differentapproaches to simultaneous confidence intervals from the literature to thesetting of three-arm non-inferiority trials and compare these methods in asimulation study. Finally we apply these methods to a real clinical trialexample.

Simultaneous confidence intervals for an extended Koch-R\"ohmel design in three-arm non-inferiority trials