0000000000336761
AUTHOR
Heiko Götte
Adaptive designs with correlated test statistics
In clinical trials, the collected observations such as clustered data or repeated measurements are often correlated. As a consequence, test statistics in a multistage design are correlated. Adaptive designs were originally developed for independent test statistics. We present a general framework for two-stage adaptive designs with correlated test statistics. We show that the significance level for the Bauer-Köhne design is inflated for positively correlated test statistics from a bivariate normal distribution. The decision boundary for the second stage can be modified so that type one error is controlled. This general concept is expandable to other adaptive designs. In order to use these de…
Sample size planning for survival prediction with focus on high-dimensional data
Sample size planning should reflect the primary objective of a trial. If the primary objective is prediction, the sample size determination should focus on prediction accuracy instead of power. We present formulas for the determination of training set sample size for survival prediction. Sample size is chosen to control the difference between optimal and expected prediction error. Prediction is carried out by Cox proportional hazards models. The general approach considers censoring as well as low-dimensional and high-dimensional explanatory variables. For dimension reduction in the high-dimensional setting, a variable selection step is inserted. If not all informative variables are included…
HLA association is different in children and adults with severe acquired aplastic anemia
Background Severe aplastic anemia (SAA) is defined as pancytopenia caused by bone marrow failure. The pathogenesis of SAA is thought to involve autoimmune processes. Increased susceptibility to autoimmunity has been shown to be associated with several different HLA alleles. In SAA, few large studies based on data mainly from adults describe a positive HLA correlation with HLA-DR2 (DRB1*15) and HLA-B14. Procedure This study explored the HLA constitution of 181 children with SAA who were enrolled in the prospective multi-center study SAA94 between January 1994 and January 2002. The control group consisted of 303 healthy individuals of comparable demographic background. Allelic frequencies bet…