19,608 research outputs found
Simulated Clinical Trias: some design issues
Simulation is widely used to investigate real-world systems in a large number of fields, including clinical trials for drug development, since real trials are costly, frequently fail and may lead to serious side effects. This paper is a survey of the statistical issues arising in these simulated trials. We illustrate the broad applicability of this investigation tool by means of examples selected from the literature. We discuss the aims and the peculiarities of the simulation models used in this context, including a brief mention of the use of metamodels. Of special interest is the topic of the design of the virtual experiments, stressing similarities and differences with the design of real life trials. Since it is important for a computerized model to possess a satisfactory range of accuracy consistent with its intended application, real data provided by physical experiments are used to confirm the simulator : we illustrate validating techniques through a number of examples. We end the paper with some challenging questions on the scientificity, ethics and effectiveness of simulation in the clinical research, and the interesting research problem of how to integrate simulated and physical experiments in a clinical context.Simulation models; pharmacokinetics; pharmacodynamics; model validation; experimental design, ethics. Modelli di simulazione; farmacocinetica; farmacodinamica; validazione; disegno degli esperimenti; etica.
Bayesian Regularisation in Structured Additive Regression Models for Survival Data
During recent years, penalized likelihood approaches have attracted a lot of interest both in the area of semiparametric regression and for the regularization of high-dimensional regression models. In this paper, we introduce a Bayesian formulation that allows to combine both aspects into a joint regression model with a focus on hazard regression for survival times. While Bayesian penalized splines form the basis for estimating nonparametric and flexible time-varying effects, regularization of high-dimensional covariate vectors is based on scale mixture of normals priors. This class of priors allows to keep a (conditional) Gaussian prior for regression coefficients on the predictor stage of the model but introduces suitable mixture distributions for the Gaussian variance to achieve regularization. This scale mixture property allows to device general and adaptive Markov chain Monte Carlo simulation algorithms for fitting a variety of hazard regression models. In particular, unifying algorithms based on iteratively weighted least squares proposals can be employed both for regularization and penalized semiparametric function estimation. Since sampling based estimates do no longer have the variable selection property well-known for the Lasso in frequentist analyses, we additionally consider spike and slab priors that introduce a further mixing stage that allows to separate between influential and redundant parameters. We demonstrate the different shrinkage properties with three simulation settings and apply the methods to the PBC Liver dataset
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On Nonregularized Estimation of Psychological Networks.
An important goal for psychological science is developing methods to characterize relationships between variables. Customary approaches use structural equation models to connect latent factors to a number of observed measurements, or test causal hypotheses between observed variables. More recently, regularized partial correlation networks have been proposed as an alternative approach for characterizing relationships among variables through off-diagonal elements in the precision matrix. While the graphical Lasso (glasso) has emerged as the default network estimation method, it was optimized in fields outside of psychology with very different needs, such as high dimensional data where the number of variables (p) exceeds the number of observations (n). In this article, we describe the glasso method in the context of the fields where it was developed, and then we demonstrate that the advantages of regularization diminish in settings where psychological networks are often fitted ( p≪n ). We first show that improved properties of the precision matrix, such as eigenvalue estimation, and predictive accuracy with cross-validation are not always appreciable. We then introduce nonregularized methods based on multiple regression and a nonparametric bootstrap strategy, after which we characterize performance with extensive simulations. Our results demonstrate that the nonregularized methods can be used to reduce the false-positive rate, compared to glasso, and they appear to provide consistent performance across sparsity levels, sample composition (p/n), and partial correlation size. We end by reviewing recent findings in the statistics literature that suggest alternative methods often have superior performance than glasso, as well as suggesting areas for future research in psychology. The nonregularized methods have been implemented in the R package GGMnonreg
Simulated Clinical Trias: some design issues
Simulation is widely used to investigate real-world systems in a large number of fields, including clinical trials for drug development, since real trials are costly, frequently fail and may lead to serious side effects. This paper is a survey of the statistical issues arising in these simulated trials. We illustrate the broad applicability of this investigation tool by means of examples selected from the literature. We discuss the aims and the peculiarities of the simulation models used in this context, including a brief mention of the use of metamodels. Of special interest is the topic of the design of the virtual experiments, stressing similarities and differences with the design of real life trials.
Since it is important for a computerized model to possess a satisfactory range of accuracy consistent with its intended application, real data provided by physical experiments are used to confirm the simulator: we illustrate validating techniques through a number of examples. We end the paper with some challenging questions on the scientificity, ethics and effectiveness of simulation in the clinical research, and the interesting research problem of how to integrate simulated and physical experiments in a clinical context
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