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This paper investigates the properties of the most common form of reinforcement learning (the " basic model " of Erev and Roth, American Economic Review, 88, 848-881, 1998). Stochastic approximation theory has been used to analyse the local stability of fixed points under this learning process. However, as we show, when such points are on the boundary of(More)
OBJECTIVE To assess the inter-rater and intra-rater reliability and validity of the original and a modified Medical Research Council scale for testing muscle strength in radial palsy. DESIGN Prospective, randomized validation study. PATIENTS Thirty-one patients with peripheral paresis of radial innervated forearm muscles were included. METHODS Wrist(More)
For clinical trials with multiple treatment arms or endpoints a variety of sequentially rejective, weighted Bonferroni-type tests have been proposed, such as gatekeeping procedures, fixed sequence tests, and fallback procedures. They allow to map the difference in importance as well as the relationship between the various research questions onto an adequate(More)
Clinical trials incorporating treatment selection at pre-specified interim analyses allow to integrate two clinical studies into a single, confirmatory study. In an adaptive interim analysis, treatment arms are selected based on interim data as well as external information. The specific selection rule does not need to be pre-specified in advance in order to(More)
The confirmatory analysis of pre-specified multiple hypotheses has become common in pivotal clinical trials. In the recent past multiple test procedures have been developed that reflect the relative importance of different study objectives, such as fixed sequence, fallback, and gatekeeping procedures. In addition, graphical approaches have been proposed(More)
We consider the situation where in a first stage of a clinical trial several treatments are compared with a single control and the 'best' treatment(s) are selected in an interim analysis to be carried on to the second stage. We quantify the mean bias and mean square error of the conventional estimates after selection depending on the number of treatments(More)
MOTIVATION When a large number of hypotheses are investigated the false discovery rate (FDR) is commonly applied in gene expression analysis or gene association studies. Conventional single-stage designs may lack power due to low sample sizes for the individual hypotheses. We propose two-stage designs where the first stage is used to screen the 'promising'(More)
STUDY DESIGN Electromyographic and biomechanical methods were utilized to investigate correlations between indexes of localized muscle fatigue and changes in the kinematics and kinetics of motion during a cyclic lifting task. SUMMARY OF BACKGROUND DATA Recent advances in time-frequency analysis procedures for electromyographicic signal processing provide(More)
BACKGROUND Since the first methodological publications on adaptive study design approaches in the 1990s, the application of these approaches in drug development has raised increasing interest among academia, industry and regulators. The European Medicines Agency (EMA) as well as the Food and Drug Administration (FDA) have published guidance documents(More)
If the response to treatment depends on genetic biomarkers, it is important to identify predictive biomarkers that define (sub-)populations where the treatment has a positive benefit risk balance. One approach to determine relevant subpopulations are subgroup analyses where the treatment effect is estimated in biomarker positive and biomarker negative(More)