This article has been cited by other articles in PMC. They reject whenever the classical test rejects but allow for inference also in settings where only a subset of endpoints show a significant effect.
Keywords: multiple endpoints, multiple testing, diagonally trimmed Simes test, Rüger test, small populations 1. Introduction In many settings it is not sufficient to show superiority of an experimental treatment compared with a control single sided lower confidence level a single endpoint, but multiple endpoints need to be considered to demonstrate benefit.
No adjustment of the individual significance level single sided lower confidence level correct for multiple testing is required in this setting 4.
It has been shown that requiring a proof of efficacy in several endpoints in general has a negative impact on the power of the study 56. In diseases with a high prevalence, such as Alzheimer or multiple sclerosis, this can be addressed by increasing the sample size, but in rare diseases, this may not be a feasible option.
Kordzakhia et al. What can be inferred in such a trial if only a subset of the endpoints meet the efficacy criterion?
Übersetzung für "sided test" im Deutsch
One approach to allow for inference if the main objective is not met is hierarchical testing 10 For the proof, we show a general result on the trivariate normal distribution which gives a uniform improvement of the Rüger test 12 of the intersection of three elementary hypotheses for multivariate normal test statistics.
A further application of the fallback tests is a procedure that has been proposed for the assessment of diagnostics.
In this setting, studies with three readers that diagnose the same group of patients have been proposed. We show that this is a valid test for the global null hypothesis that for all three readers the sensitivity or specificity or both lie below the threshold.
Note that the term fallback test has been used for a generalization of the hierarchical test for a primary and several ordered secondary endpoints that allows one to continue testing in the hierarchical order even if the test for the primary endpoint does not reject Technical proofs are given in the Appendix.