A course in constructing effective displays of data for pharmaceutical research personnel

Interpreting data and communicating effectively through graphs and tables are requisite skills for statisticians and non‐statisticians in the pharmaceutical industry. However, the quality of visual displays of data in the medical and pharmaceutical literature and at scientific conferences is severely lacking. We describe an interactive, workshop‐driven, 2‐day short course that we constructed for pharmaceutical research personnel to learn these skills. The examples in the course and the workshop datasets source from our professional experiences, the scientific literature, and the mass media. During the course, the participants are exposed to and gain hands‐on experience with the principles of visual and graphical perception, design, and construction of both graphic and tabular displays of quantitative and qualitative information. After completing the course, with a critical eye, the participants are able to construct, revise, critique, and interpret graphic and tabular displays according to an extensive set of guidelines. Copyright © 2013 John Wiley & Sons, Ltd.     

Fast and Accurate Inference for the Smoothing Parameter in Semiparametric Models

A fast and accurate method of confidence interval construction for the smoothing parameter in penalised spline and partially linear models is proposed. The method is akin to a parametric percentile bootstrap where Monte Carlo simulation is replaced by saddlepoint approximation, and can therefore be viewed as an approximate bootstrap. It is applicable in a quite general setting, requiring only that the underlying estimator be the root of an estimating equation that is a quadratic form in normal random variables. This is the case under a variety of optimality criteria such as those commonly denoted by maximum likelihood (ML), restricted ML (REML), generalized cross validation (GCV) and Akaike's information criteria (AIC). Simulation studies reveal that under the ML and REML criteria, the method delivers a near‐exact performance with computational speeds that are an order of magnitude faster than existing exact methods, and two orders of magnitude faster than a classical bootstrap. Perhaps most importantly, the proposed method also offers a computationally feasible alternative when no known exact or asymptotic methods exist, e.g. GCV and AIC. An application is illustrated by applying the methodology to well‐known fossil data. Giving a range of plausible smoothed values in this instance can help answer questions about the statistical significance of apparent features in the data.     

Automatic locally adaptive smoothing for tree-based set estimation

Tree-based methods similar to CART have recently been utilized for problems in which the main goal is to estimate some set of interest. It is often the case that the boundary of the true set is smooth in some sense, however tree-based estimates will not be smooth, as they will be a union of ‘boxes’. We propose a general methodology for smoothing such sets that allows for varying levels of smoothness on the boundary automatically. The method is similar to the idea underlying support vector machines, which is applying a computationally simple technique to data after a non-linear mapping to produce smooth estimates in the original space. In particular, we consider the problem of level-set estimation for regression functions and the dyadic tree-based method of Willett and Nowak [Minimax optimal level-set estimation, IEEE Trans. Image Process. 16 (2007), pp. 2965–2979].     

Case–control genome-wide joint association study using semiparametric empirical model and approximate Bayes factor

We propose a semiparametric approach for the analysis of case–control genome-wide association study. Parametric components are used to model both the conditional distribution of the case status given the covariates and the distribution of genotype counts, whereas the distribution of the covariates are modelled nonparametrically. This yields a direct and joint modelling of the case status, covariates and genotype counts, and gives a better understanding of the disease mechanism and results in more reliable conclusions. Side information, such as the disease prevalence, can be conveniently incorporated into the model by an empirical likelihood approach and leads to more efficient estimates and a powerful test in the detection of disease-associated SNPs. Profiling is used to eliminate a nuisance nonparametric component, and the resulting profile empirical likelihood estimates are shown to be consistent and asymptotically normal. For the hypothesis test on disease association, we apply the approximate Bayes factor (ABF) which is computationally simple and most desirable in genome-wide association studies where hundreds of thousands to a million genetic markers are tested. We treat the approximate Bayes factor as a hybrid Bayes factor which replaces the full data by the maximum likelihood estimates of the parameters of interest in the full model and derive it under a general setting. The deviation from Hardy–Weinberg Equilibrium (HWE) is also taken into account and the ABF for HWE using cases is shown to provide evidence of association between a disease and a genetic marker. Simulation studies and an application are further provided to illustrate the utility of the proposed methodology.     

Maximum Likelihood Estimation for Stochastic Differential Equations with Random Effects

Abstract. We consider N independent stochastic processes (X _i (t), t ∈ [0,T _i ]), i=1,…, N, defined by a stochastic differential equation with drift term depending on a random variable φ _i . The distribution of the random effect φ _i depends on unknown parameters which are to be estimated from the continuous observation of the processes X_i. We give the expression of the exact likelihood. When the drift term depends linearly on the random effect φ _i and φ _i has Gaussian distribution, an explicit formula for the likelihood is obtained. We prove that the maximum likelihood estimator is consistent and asymptotically Gaussian, when T _i =T for all i and N tends to infinity. We discuss the case of discrete observations. Estimators are computed on simulated data for several models and show good performances even when the length time interval of observations is not very large.     

Testing Monotonicity of Regression Functions – An Empirical Process Approach

We propose several new tests for monotonicity of regression functions based on different empirical processes of residuals and pseudo‐residuals. The residuals are obtained from an unconstrained kernel regression estimator whereas the pseudo‐residuals are obtained from an increasing regression estimator. Here, in particular, we consider a recently developed simple kernel‐based estimator for increasing regression functions based on increasing rearrangements of unconstrained non‐parametric estimators. The test statistics are estimated distance measures between the regression function and its increasing rearrangement. We discuss the asymptotic distributions, consistency and small sample performances of the tests.     

Flexible Copula Density Estimation with Penalized Hierarchical B‐splines

The paper introduces a new method for flexible spline fitting for copula density estimation. Spline coefficients are penalized to achieve a smooth fit. To weaken the curse of dimensionality, instead of a full tensor spline basis, a reduced tensor product based on so called sparse grids (Notes Numer. Fluid Mech. Multidiscip. Des., 31, 1991, 241‐251) is used. To achieve uniform margins of the copula density, linear constraints are placed on the spline coefficients, and quadratic programming is used to fit the model. Simulations and practical examples accompany the presentation.     

Statisticians Can Matter

Statisticians fall far short of their potential as guides to enlightened decision making in business. Two important explanations are: (1) Decision makers are often more easily convinced by concrete examples, however fragmentary and misleading, than by competent statistical analysis. (2) The effective use of statistics in the process of decision making requires hard thinking by decision makers, thinking that cannot be delegated entirely to the statistical specialist. Modern developments in interactive statistical computing may help to reduce the force of these limitations on exploitation of statistics; used properly, computing can encourage, almost force, the student or business user of statistics to think statistically.     

Asymptotically Optimal Nonparametric Empirical Bayes Via Predictive Recursion

An empirical Bayes problem has an unknown prior to be estimated from data. The predictive recursion (PR) algorithm provides fast nonparametric estimation of mixing distributions and is ideally suited for empirical Bayes applications. This article presents a general notion of empirical Bayes asymptotic optimality, and it is shown that PR-based procedures satisfy this property under certain conditions. As an application, the problem of in-season prediction of baseball batting averages is considered. There the PR-based empirical Bayes rule performs well in terms of prediction error and ability to capture the distribution of the latent features.