0000000000330816
AUTHOR
Siegfried Kropf
Tests for Differentiation in Gene Expression Using a Data-Driven Order or Weights for Hypotheses
In the analysis of gene expression by microarrays there are usually few subjects, but high-dimensional data. By means of techniques, such as the theory of spherical tests or with suitable permutation tests, it is possible to sort the endpoints or to give weights to them according to specific criteria determined by the data while controlling the multiple type I error rate. The procedures developed so far are based on a sequential analysis of weighted p-values (corresponding to the endpoints), including the most extreme situation of weighting leading to a complete order of p-values. When the data for the endpoints have approximately equal variances, these procedures show good power properties…
Rationale for and design of the CREATIVE-AF trial: randomized, double-blind, placebo-controlled, crossover study of the effect of irbesartan on oxidative stress and adhesion molecules in patients with persistent atrial fibrillation.
Background and objective: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Recent studies suggest there is an angiotensin II-dependent increase in adhesion molecules and oxidative stress parameters during AF. These alterations appear to contribute to inflammatory and prothrombotic changes in the atrial endocardium (‘endocardial remodelling’), suggesting that patients with increased levels of these factors might be at risk of thromboembolic events. The purpose of the CREATIVE-AF (Impact of Irbesartan on Oxidative Stress and C-Reactive Protein Levels in Patients with Persistent Atrial Fibrillation) trial is to prove the principle concept that blockade of angiotensin II type 1 r…
Multiple Comparisons of Treatments with Stable Multivariate Tests in a Two‐Stage Adaptive Design, Including a Test for Non‐Inferiority
The application of stabilized multivariate tests is demonstrated in the analysis of a two-stage adaptive clinical trial with three treatment arms. Due to the clinical problem, the multiple comparisons include tests of superiority as well as a test for non-inferiority, where non-inferiority is (because of missing absolute tolerance limits) expressed as linear contrast of the three treatments. Special emphasis is paid to the combination of the three sources of multiplicity - multiple endpoints, multiple treatments, and two stages of the adaptive design. Particularly, the adaptation after the first stage comprises a change of the a-priori order of hypotheses.