Confidence distributions applied to propagating uncertainty to inference based on estimating the local false discovery rate: A fiducial continuum from confidence sets to empirical Bayes set estimates as the number of comparisons increases

Empirical Bayes estimates of the local false discovery rate can reflect uncertainty about the estimated prior by supplementing their Bayesian posterior probabilities with confidence levels as posterior probabilities. This use of coherent fiducial inference with hierarchical models generates set estimators that propagate uncertainty to varying degrees. Some of the set estimates approach estimates from plug-in empirical Bayes methods for high numbers of comparisons and can come close to the usual confidence sets given a sufficiently low number of comparisons.     

Semiparametric hierarchical selection models for bayesian meta analysis

Meta-analysis refers to quantitative methods for combining results from independent studies in order to draw overall conclusions. Hierarchical models including selection models are introduced and shown to be useful in such Bayesian meta-analysis. Semiparametric hierarchical models are proposed using the Dirichlet process prior. These rich class of models combine the information of independent studies, allowing investigation of variability both between and within studies, and weight function. Here we investigate sensitivity of results to unobserved studies by considering a hierarchical selection model with including unknown weight function and use Markov chain Monte Carlo methods to develop inference for the parameters of interest. Using Bayesian method, this model is used on a meta-analysis of twelve studies comparing the effectiveness of two different types of flouride, in preventing cavities. Clinical informative prior is assumed. Summaries and plots of model parameters are analyzed to address questions of interest.     

Hierarchical Bayesian meta-analysis models for cross-platform microarray studies

The development of new technologies to measure gene expression has been calling for statistical methods to integrate findings across multiple-platform studies. A common goal of microarray analysis is to identify genes with differential expression between two conditions, such as treatment versus control. Here, we introduce a hierarchical Bayesian meta-analysis model to pool gene expression studies from different microarray platforms: spotted DNA arrays and short oligonucleotide arrays. The studies have different array design layouts, each with multiple sources of data replication, including repeated experiments, slides and probes. Our model produces the gene-specific posterior probability of differential expression, which is the basis for inference. In simulations combining two and five independent studies, our meta-analysis model outperformed separate analyses for three commonly used comparison measures; it also showed improved receiver operating characteristic curves. When combining spotted DNA and CombiMatrix short oligonucleotide array studies of Geobacter sulfurreducens, our meta-analysis model discovered more genes for fixed thresholds of posterior probability of differential expression and Bayesian false discovery than individual study analyses. We also examine an alternative model and compare models using the deviance information criterion.     

A re-evaluation of random-effects meta-analysis

Summary.  Meta-analysis in the presence of unexplained heterogeneity is frequently undertaken by using a random-effects model, in which the effects underlying different studies are assumed to be drawn from a normal distribution. Here we discuss the justification and interpretation of such models, by addressing in turn the aims of estimation, prediction and hypothesis testing. A particular issue that we consider is the distinction between inference on the mean of the random-effects distribution and inference on the whole distribution. We suggest that random-effects meta-analyses as currently conducted often fail to provide the key results, and we investigate the extent to which distribution-free, classical and Bayesian approaches can provide satisfactory methods. We conclude that the Bayesian approach has the advantage of naturally allowing for full uncertainty, especially for prediction. However, it is not without problems, including computational intensity and sensitivity to a priori judgements. We propose a simple prediction interval for classical meta-analysis and offer extensions to standard practice of Bayesian meta-analysis, making use of an example of studies of 'set shifting' ability in people with eating disorders.     

Covariance Matrix Estimation via Network Structure

In this article, we employ a regression formulation to estimate the high-dimensional covariance matrix for a given network structure. Using prior information contained in the network relationships, we model the covariance as a polynomial function of the symmetric adjacency matrix. Accordingly, the problem of estimating a high-dimensional covariance matrix is converted to one of estimating low dimensional coefficients of the polynomial regression function, which we can accomplish using ordinary least squares or maximum likelihood. The resulting covariance matrix estimator based on the maximum likelihood approach is guaranteed to be positive definite even in finite samples. Under mild conditions, we obtain the theoretical properties of the resulting estimators. A Bayesian information criterion is also developed to select the order of the polynomial function. Simulation studies and empirical examples illustrate the usefulness of the proposed methods.     

On analysis of binary response data in longitudinal factorial studies

Binary data are commonly used as responses to assess the effects of independent variables in longitudinal factorial studies. Such effects can be assessed in terms of the rate difference (RD), the odds ratio (OR), or the rate ratio (RR). Traditionally, the logistic regression seems always a recommended method with statistical comparisons made in terms of the OR. Statistical inference in terms of the RD and RR can then be derived using the delta method. However, this approach is hard to realize when repeated measures occur. To obtain statistical inference in longitudinal factorial studies, the current article shows that the mixed-effects model for repeated measures, the logistic regression for repeated measures, the log-transformed regression for repeated measures, and the rank-based methods are all valid methods that lead to inference in terms of the RD, OR, and RR, respectively. Asymptotic linear relationships between the estimators of the regression coefficients of these models are derived when the weight (working covariance) matrix is an identity matrix. Conditions for the Wald-type tests to be asymptotically equivalent in these models are provided and powers were compared using simulation studies. A phase III clinical trial is used to illustrate the investigated methods with corresponding SAS® code supplied.     

Bayesian analysis of joint mean and covariance models for longitudinal data

Efficient estimation of the regression coefficients in longitudinal data analysis requires a correct specification of the covariance structure. If misspecification occurs, it may lead to inefficient or biased estimators of parameters in the mean. One of the most commonly used methods for handling the covariance matrix is based on simultaneous modeling of the Cholesky decomposition. Therefore, in this paper, we reparameterize covariance structures in longitudinal data analysis through the modified Cholesky decomposition of itself. Based on this modified Cholesky decomposition, the within-subject covariance matrix is decomposed into a unit lower triangular matrix involving moving average coefficients and a diagonal matrix involving innovation variances, which are modeled as linear functions of covariates. Then, we propose a fully Bayesian inference for joint mean and covariance models based on this decomposition. A computational efficient Markov chain Monte Carlo method which combines the Gibbs sampler and Metropolis–Hastings algorithm is implemented to simultaneously obtain the Bayesian estimates of unknown parameters, as well as their standard deviation estimates. Finally, several simulation studies and a real example are presented to illustrate the proposed methodology.     

Proper Bayes minimax estimators of the normal mean matrix with common unknown variances

This paper addresses the problem of estimating a matrix of the normal means, where the variances are unknown but common. The approach to this problem is provided by a hierarchical Bayes modeling for which the first stage prior for the means is matrix-variate normal distribution with mean zero matrix and a covariance structure and the second stage prior for the covariance is similar to Jeffreys’ rule. The resulting hierarchical Bayes estimators relative to the quadratic loss function belong to a class of matricial shrinkage estimators. Certain conditions are obtained for admissibility and minimaxity of the hierarchical Bayes estimators.     

Variational Bayes with synthetic likelihood

Synthetic likelihood is an attractive approach to likelihood-free inference when an approximately Gaussian summary statistic for the data, informative for inference about the parameters, is available. The synthetic likelihood method derives an approximate likelihood function from a plug-in normal density estimate for the summary statistic, with plug-in mean and covariance matrix obtained by Monte Carlo simulation from the model. In this article, we develop alternatives to Markov chain Monte Carlo implementations of Bayesian synthetic likelihoods with reduced computational overheads. Our approach uses stochastic gradient variational inference methods for posterior approximation in the synthetic likelihood context, employing unbiased estimates of the log likelihood. We compare the new method with a related likelihood-free variational inference technique in the literature, while at the same time improving the implementation of that approach in a number of ways. These new algorithms are feasible to implement in situations which are challenging for conventional approximate Bayesian computation methods, in terms of the dimensionality of the parameter and summary statistic.     

Explaining the behavior of joint and marginal Monte Carlo estimators in latent variable models with independence assumptions

In latent variable models parameter estimation can be implemented by using the joint or the marginal likelihood, based on independence or conditional independence assumptions. The same dilemma occurs within the Bayesian framework with respect to the estimation of the Bayesian marginal (or integrated) likelihood, which is the main tool for model comparison and averaging. In most cases, the Bayesian marginal likelihood is a high dimensional integral that cannot be computed analytically and a plethora of methods based on Monte Carlo integration (MCI) are used for its estimation. In this work, it is shown that the joint MCI approach makes subtle use of the properties of the adopted model, leading to increased error and bias in finite settings. The sources and the components of the error associated with estimators under the two approaches are identified here and provided in exact forms. Additionally, the effect of the sample covariation on the Monte Carlo estimators is examined. In particular, even under independence assumptions the sample covariance will be close to (but not exactly) zero which surprisingly has a severe effect on the estimated values and their variability. To address this problem, an index of the sample’s divergence from independence is introduced as a multivariate extension of covariance. The implications addressed here are important in the majority of practical problems appearing in Bayesian inference of multi-parameter models with analogous structures.     

Bias in Small-Sample Inference With Count-Data Models

Abstract

Both Poisson and negative binomial regression can provide quasi-likelihood estimates for coefficients in exponential-mean models that are consistent in the presence of distributional misspecification. It has generally been recommended, however, that inference be carried out using asymptotically robust estimators for the parameter covariance matrix. As with linear models, such robust inference tends to lead to over-rejection of null hypotheses in small samples. Alternative methods for estimating coefficient estimator variances are considered. No one approach seems to remove all test bias, but the results do suggest that the use of the jackknife with Poisson regression tends to be least biased for inference.     

Estimation of covariance matrices based on hierarchical inverse-Wishart priors

This paper focuses on Bayesian shrinkage methods for covariance matrix estimation. We examine posterior properties and frequentist risks of Bayesian estimators based on new hierarchical inverse-Wishart priors. More precisely, we give the conditions for the existence of the posterior distributions. Advantages in terms of numerical simulations of posteriors are shown. A simulation study illustrates the performance of the estimation procedures under three loss functions for relevant sample sizes and various covariance structures.     

Inference for two-stage adaptive treatment strategies using mixture distributions

Summary.  Treatment of complex diseases such as cancer, leukaemia, acquired immune deficiency syndrome and depression usually follows complex treatment regimes consisting of time varying multiple courses of the same or different treatments. The goal is to achieve the largest overall benefit defined by a common end point such as survival. Adaptive treatment strategy refers to a sequence of treatments that are applied at different stages of therapy based on the individual's history of covariates and intermediate responses to the earlier treatments. However, in many cases treatment assignment depends only on intermediate response and prior treatments. Clinical trials are often designed to compare two or more adaptive treatment strategies. A common approach that is used in these trials is sequential randomization. Patients are randomized on entry into available first-stage treatments and then on the basis of the response to the initial treatments are randomized to second-stage treatments, and so on. The analysis often ignores this feature of randomization and frequently conducts separate analysis for each stage. Recent literature suggested several semiparametric and Bayesian methods for inference related to adaptive treatment strategies from sequentially randomized trials. We develop a parametric approach using mixture distributions to model the survival times under different adaptive treatment strategies. We show that the estimators proposed are asymptotically unbiased and can be easily implemented by using existing routines in statistical software packages.     

Bayesian regression on non-parametric mixed-effect models with shape-restricted Bernstein polynomials

We develop a Bayesian estimation method to non-parametric mixed-effect models under shape-constrains. The approach uses a hierarchical Bayesian framework and characterizations of shape-constrained Bernstein polynomials (BPs). We employ Markov chain Monte Carlo methods for model fitting, using a truncated normal distribution as the prior for the coefficients of BPs to ensure the desired shape constraints. The small sample properties of the Bayesian shape-constrained estimators across a range of functions are provided via simulation studies. Two real data analysis are given to illustrate the application of the proposed method.     

A Bayesian approach to non-parametric monotone function estimation

Summary.  The paper proposes two Bayesian approaches to non-parametric monotone function estimation. The first approach uses a hierarchical Bayes framework and a characterization of smooth monotone functions given by Ramsay that allows unconstrained estimation. The second approach uses a Bayesian regression spline model of Smith and Kohn with a mixture distribution of constrained normal distributions as the prior for the regression coefficients to ensure the monotonicity of the resulting function estimate. The small sample properties of the two function estimators across a range of functions are provided via simulation and compared with existing methods. Asymptotic results are also given that show that Bayesian methods provide consistent function estimators for a large class of smooth functions. An example is provided involving economic demand functions that illustrates the application of the constrained regression spline estimator in the context of a multiple-regression model where two functions are constrained to be monotone.     

Avoiding 'data snooping' in multilevel and mixed effects models

Summary.  Multilevel or mixed effects models are commonly applied to hierarchical data. The level 2 residuals, which are otherwise known as random effects, are often of both substantive and diagnostic interest. Substantively, they are frequently used for institutional comparisons or rankings. Diagnostically, they are used to assess the model assumptions at the group level. Inference on the level 2 residuals, however, typically does not account for 'data snooping', i.e. for the harmful effects of carrying out a multitude of hypothesis tests at the same time. We provide a very general framework that encompasses both of the following inference problems: inference on the 'absolute' level 2 residuals to determine which are significantly different from 0, and inference on any prespecified number of pairwise comparisons. Thus, the user has the choice of testing the comparisons of interest. As our methods are flexible with respect to the estimation method that is invoked, the user may choose the desired estimation method accordingly. We demonstrate the methods with the London education authority data, the wafer data and the National Educational Longitudinal Study data.     

Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary.  We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi-likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population-average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.     

Small area estimation strategies for large population surveys: a comparison of design and model-based methods

Small area estimation (SAE) concerns with how to reliably estimate population quantities of interest when some areas or domains have very limited samples. This is an important issue in large population surveys, because the geographical areas or groups with only small samples or even no samples are often of interest to researchers and policy-makers. For example, large population health surveys, such as Behavioural Risk Factor Surveillance System and Ohio Mecaid Assessment Survey (OMAS), are regularly conducted for monitoring insurance coverage and healthcare utilization. Classic approaches usually provide accurate estimators at the state level or large geographical region level, but they fail to provide reliable estimators for many rural counties where the samples are sparse. Moreover, a systematic evaluation of the performances of the SAE methods in real-world setting is lacking in the literature. In this paper, we propose a Bayesian hierarchical model with constraints on the parameter space and show that it provides superior estimators for county-level adult uninsured rates in Ohio based on the 2012 OMAS data. Furthermore, we perform extensive simulation studies to compare our methods with a collection of common SAE strategies, including direct estimators, synthetic estimators, composite estimators, and Datta GS, Ghosh M, Steorts R, Maples J.'s [Bayesian benchmarking with applications to small area estimation. Test 2011;20(3):574–588] Bayesian hierarchical model-based estimators. To set a fair basis for comparison, we generate our simulation data with characteristics mimicking the real OMAS data, so that neither model-based nor design-based strategies use the true model specification. The estimators based on our proposed model are shown to outperform other estimators for small areas in both simulation study and real data analysis.     

Assessment of vague and noninformative priors for Bayesian estimation of the realized random effects in random-effects meta-analysis

Random-effects meta-analysis has become a well-established tool applied in many areas, for example, when combining the results of several clinical studies on a treatment effect. Typically, the inference aims at the common mean and the amount of heterogeneity. In some applications, the laboratory effects are of interest, for example, when assessing uncertainties quoted by laboratories participating in an interlaboratory comparison in metrology. We consider the Bayesian estimation of the realized random effects in random-effects meta-analysis. Several vague and noninformative priors are examined as well as a proposed novel one. Conditions are established that ensure propriety of the posteriors for the realized random effects. We present extensive simulation results that assess the inference in dependence on the choice of prior as well as mis-specifications in the statistical model. Overall good performance is observed for all priors with the novel prior showing the most promising results. Finally, the uncertainties reported by eleven national metrology institutes and universities for their measurements on the Newtonian constant of gravitation are assessed.     

C337. Misspecified location and scale. 11. independence of and s2

A hierarchical Bayesian approach to the problem of estimating the largest normal mean is considered. Calculation of the posterior mean and the posterior variance involves, at worst, 3-dimensional numerical integration, for which an efficient Monte Carlo method of evaluation is given. An example is presented to illustrate the methodology. In the two populations case, computation of the posterior estimates can be substantially simplified and in special cases can actually be performed using closed form solutions. A simulation study has been done to compare mean square errors of some hierarchical Bayesian estimators that are expressed in closed forms and several existing estimators of the larger mean.