15,238 research outputs found

    Optimal designs for active controlled dose finding trials with efficacy-toxicity outcomes

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    Nonlinear regression models addressing both efficacy and toxicity outcomes are increasingly used in dose-finding trials, such as in pharmaceutical drug development. However, research on related experimental design problems for corresponding active controlled trials is still scarce. In this paper we derive optimal designs to estimate efficacy and toxicity in an active controlled clinical dose finding trial when the bivariate continuous outcomes are modeled either by polynomials up to degree 2, the Michaelis- Menten model, the Emax model, or a combination thereof. We determine upper bounds on the number of different doses levels required for the optimal design and provide conditions under which the boundary points of the design space are included in the optimal design. We also provide an analytical description of the minimally supported DD-optimal designs and show that they do not depend on the correlation between the bivariate outcomes. We illustrate the proposed methods with numerical examples and demonstrate the advantages of the DD-optimal design for a trial, which has recently been considered in the literature.Comment: Keywords and Phrases: Active controlled trials, dose finding, optimal design, admissible design, Emax model, Equivalence theorem, Particle swarm optimization, Tchebycheff syste

    Combining Forecasts Based on Multiple Encompassing Tests in a Macroeconomic Core System

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    We investigate whether and to what extent multiple encompassing tests may help determine weights for forecast averaging in a standard vector autoregressive setting. To this end we consider a new test-based procedure, which assigns non-zero weights to candidate models that add information not covered by other models. The potential benefits of this procedure are explored in extensive Monte Carlo simulations using realistic designs that are adapted to U.K. and to French macroeconomic data. The real economic growth rates of these two countries serve as the target series to be predicted. Generally, we find that the test-based averaging of forecasts yields a performance that is comparable to a simple uniform weighting of individual models. In one of our role-model economies, test-based averaging achieves some advantages in small samples. In larger samples, pure prediction models outperform forecast averages.Combining forecasts, encompassing tests, model selection, time series
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