An objective Bayesian analysis of the two-parameter half-logistic distribution based on progressively type-II censored samples

This paper develops an objective Bayesian analysis method for estimating unknown parameters of the half-logistic distribution when a sample is available from the progressively Type-II censoring scheme. Noninformative priors such as Jeffreys and reference priors are derived. In addition, derived priors are checked to determine whether they satisfy probability-matching criteria. The Metropolis–Hasting algorithm is applied to generate Markov chain Monte Carlo samples from these posterior density functions because marginal posterior density functions of each parameter cannot be expressed in an explicit form. Monte Carlo simulations are conducted to investigate frequentist properties of estimated models under noninformative priors. For illustration purposes, a real data set is presented, and the quality of models under noninformative priors is evaluated through posterior predictive checking.     

Objective Testing Procedures in Linear Models: Calibration of the p-values

Abstract.  An optimal Bayesian decision procedure for testing hypothesis in normal linear models based on intrinsic model posterior probabilities is considered. It is proven that these posterior probabilities are simple functions of the classical F -statistic, thus the evaluation of the procedure can be carried out analytically through the frequentist analysis of the posterior probability of the null. An asymptotic analysis proves that, under mild conditions on the design matrix, the procedure is consistent. For any testing hypothesis it is also seen that there is a one-to-one mapping – which we call calibration curve – between the posterior probability of the null hypothesis and the classical bi p -value. This curve adds substantial knowledge about the possible discrepancies between the Bayesian and the p -value measures of evidence for testing hypothesis. It permits a better understanding of the serious difficulties that are encountered in linear models for interpreting the p -values. A specific illustration of the variable selection problem is given.     

Addressing potential prior‐data conflict when using informative priors in proof‐of‐concept studies

Bayesian methods are increasingly used in proof‐of‐concept studies. An important benefit of these methods is the potential to use informative priors, thereby reducing sample size. This is particularly relevant for treatment arms where there is a substantial amount of historical information such as placebo and active comparators. One issue with using an informative prior is the possibility of a mismatch between the informative prior and the observed data, referred to as prior‐data conflict. We focus on two methods for dealing with this: a testing approach and a mixture prior approach. The testing approach assesses prior‐data conflict by comparing the observed data to the prior predictive distribution and resorting to a non‐informative prior if prior‐data conflict is declared. The mixture prior approach uses a prior with a precise and diffuse component. We assess these approaches for the normal case via simulation and show they have some attractive features as compared with the standard one‐component informative prior. For example, when the discrepancy between the prior and the data is sufficiently marked, and intuitively, one feels less certain about the results, both the testing and mixture approaches typically yield wider posterior‐credible intervals than when there is no discrepancy. In contrast, when there is no discrepancy, the results of these approaches are typically similar to the standard approach. Whilst for any specific study, the operating characteristics of any selected approach should be assessed and agreed at the design stage; we believe these two approaches are each worthy of consideration. Copyright © 2015 John Wiley & Sons, Ltd.     

Statistical modeling for Bayesian extrapolation of adult clinical trial information in pediatric drug evaluation

Children represent a large underserved population of “therapeutic orphans,” as an estimated 80% of children are treated off‐label. However, pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Among many efforts trying to remove these barriers, increased recent attention has been paid to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. The Bayesian statistical paradigm is natural in this setting, as it permits the combining (or “borrowing”) of information across disparate sources, such as the adult and pediatric data. In this paper, authored by the pediatric subteam of the Drug Information Association Bayesian Scientific Working Group and Adaptive Design Working Group, we develop, illustrate, and provide suggestions on Bayesian statistical methods that could be used to design improved pediatric development programs that use all available information in the most efficient manner. A variety of relevant Bayesian approaches are described, several of which are illustrated through 2 case studies: extrapolating adult efficacy data to expand the labeling for Remicade to include pediatric ulcerative colitis and extrapolating adult exposure‐response information for antiepileptic drugs to pediatrics.     

Restricted most powerful Bayesian tests for linear models

Uniformly most powerful Bayesian tests (UMPBTs) are a new class of Bayesian tests in which null hypotheses are rejected if their Bayes factor exceeds a specified threshold. The alternative hypotheses in UMPBTs are defined to maximize the probability that the null hypothesis is rejected. Here, we generalize the notion of UMPBTs by restricting the class of alternative hypotheses over which this maximization is performed, resulting in restricted most powerful Bayesian tests (RMPBTs). We then derive RMPBTs for linear models by restricting alternative hypotheses to g priors. For linear models, the rejection regions of RMPBTs coincide with those of usual frequentist F‐tests, provided that the evidence thresholds for the RMPBTs are appropriately matched to the size of the classical tests. This correspondence supplies default Bayes factors for many common tests of linear hypotheses. We illustrate the use of RMPBTs for ANOVA tests and t‐tests and compare their performance in numerical studies.     

Bayesian ikference procedures derived via the concept of relative surprise

We consider the problem of deriving Bayesian inference procedures via the concept of relative surprise. The mathematical concept of surprise has been developed by I.J. Good in a long sequence of papers. We make a modification to this development that permits the avoidance of a serious defect; namely, the change of variable problem. We apply relative surprise to the development of estimation, hypothesis testing and model checking procedures. Important advantages of the relative surprise approach to inference include the lack of dependence on a particular loss function and complete freedom to the statistician in the choice of prior for hypothesis testing problems. Links are established with common Bayesian inference procedures such as highest posterior density regions, modal estimates and Bayes factors. From a practical perspective new inference procedures arise that possess good properties.     

A general approach to heteroscedastic linear regression

Our article presents a general treatment of the linear regression model, in which the error distribution is modelled nonparametrically and the error variances may be heteroscedastic, thus eliminating the need to transform the dependent variable in many data sets. The mean and variance components of the model may be either parametric or nonparametric, with parsimony achieved through variable selection and model averaging. A Bayesian approach is used for inference with priors that are data-based so that estimation can be carried out automatically with minimal input by the user. A Dirichlet process mixture prior is used to model the error distribution nonparametrically; when there are no regressors in the model, the method reduces to Bayesian density estimation, and we show that in this case the estimator compares favourably with a well-regarded plug-in density estimator. We also consider a method for checking the fit of the full model. The methodology is applied to a number of simulated and real examples and is shown to work well.     

Comparison of testing procedures utilizing P-values and Bayes factors in some common situations

Bayesian alternatives to classical tests for several testing problems are considered. One-sided and two-sided sets of hypotheses are tested concerning an exponential parameter, a Binomial proportion, and a normal mean. Hierarchical Bayes and noninformative Bayes procedures are compared with the appropriate classical procedure, either the uniformly most powerful test or the likelihood ratio test, in the different situations. The hierarchical prior employed is the conjugate prior at the first stage with the mean being the test parameter and a noninformative prior at the second stage for the hyper parameter(s) of the first stage prior. Fair comparisons are attempted in which fair means the likelihood of making a type I error is approximately the same for the different testing procedures; once this condition is satisfied, the power of the different tests are compared, the larger the power, the better the test. This comparison is difficult in the two-sided case due to the unsurprising discrepancy between Bayesian and classical measures of evidence that have been discussed for years. The hierarchical Bayes tests appear to compete well with the typical classical test in the one-sided cases.     

Bayesian predictive power: choice of prior and some recommendations for its use as probability of success in drug development

Bayesian predictive power, the expectation of the power function with respect to a prior distribution for the true underlying effect size, is routinely used in drug development to quantify the probability of success of a clinical trial. Choosing the prior is crucial for the properties and interpretability of Bayesian predictive power. We review recommendations on the choice of prior for Bayesian predictive power and explore its features as a function of the prior. The density of power values induced by a given prior is derived analytically and its shape characterized. We find that for a typical clinical trial scenario, this density has a u‐shape very similar, but not equal, to a β‐distribution. Alternative priors are discussed, and practical recommendations to assess the sensitivity of Bayesian predictive power to its input parameters are provided. Copyright © 2016 John Wiley & Sons, Ltd.     

Adaptive Bayesian Procedures Using Random Series Priors

We consider a general class of prior distributions for nonparametric Bayesian estimation which uses finite random series with a random number of terms. A prior is constructed through distributions on the number of basis functions and the associated coefficients. We derive a general result on adaptive posterior contraction rates for all smoothness levels of the target function in the true model by constructing an appropriate ‘sieve’ and applying the general theory of posterior contraction rates. We apply this general result on several statistical problems such as density estimation, various nonparametric regressions, classification, spectral density estimation and functional regression. The prior can be viewed as an alternative to the commonly used Gaussian process prior, but properties of the posterior distribution can be analysed by relatively simpler techniques. An interesting approximation property of B‐spline basis expansion established in this paper allows a canonical choice of prior on coefficients in a random series and allows a simple computational approach without using Markov chain Monte Carlo methods. A simulation study is conducted to show that the accuracy of the Bayesian estimators based on the random series prior and the Gaussian process prior are comparable. We apply the method on Tecator data using functional regression models.     

Using Bayesian analysis in repeated preclinical in vivo studies for a more effective use of animals

Whilst innovative Bayesian approaches are increasingly used in clinical studies, in the preclinical area Bayesian methods appear to be rarely used in the reporting of pharmacology data. This is particularly surprising in the context of regularly repeated in vivo studies where there is a considerable amount of data from historical control groups, which has potential value. This paper describes our experience with introducing Bayesian analysis for such studies using a Bayesian meta‐analytic predictive approach. This leads naturally either to an informative prior for a control group as part of a full Bayesian analysis of the next study or using a predictive distribution to replace a control group entirely. We use quality control charts to illustrate study‐to‐study variation to the scientists and describe informative priors in terms of their approximate effective numbers of animals. We describe two case studies of animal models: the lipopolysaccharide‐induced cytokine release model used in inflammation and the novel object recognition model used to screen cognitive enhancers, both of which show the advantage of a Bayesian approach over the standard frequentist analysis. We conclude that using Bayesian methods in stable repeated in vivo studies can result in a more effective use of animals, either by reducing the total number of animals used or by increasing the precision of key treatment differences. This will lead to clearer results and supports the “3Rs initiative” to Refine, Reduce and Replace animals in research. Copyright © 2016 John Wiley & Sons, Ltd.     

Non‐inferiority and networks: inferring efficacy from a web of data

In the absence of placebo‐controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non‐inferiority to an active control; that is, the test treatment is not worse than the active control by a pre‐specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non‐inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta‐analysis that models the uncertainty and heterogeneity of the historical trials into the non‐inferiority trial in a data‐driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non‐inferiority testing are discussed that are analogs of the synthesis and fixed‐margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non‐inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non‐inferiority. Copyright © 2015 John Wiley & Sons, Ltd.     

Bayesian Conditional Mean Estimation in Log‐Normal Linear Regression Models with Finite Quadratic Expected Loss

Log‐normal linear regression models are popular in many fields of research. Bayesian estimation of the conditional mean of the dependent variable is problematic as many choices of the prior for the variance (on the log‐scale) lead to posterior distributions with no finite moments. We propose a generalized inverse Gaussian prior for this variance and derive the conditions on the prior parameters that yield posterior distributions of the conditional mean of the dependent variable with finite moments up to a pre‐specified order. The conditions depend on one of the three parameters of the suggested prior; the other two have an influence on inferences for small and medium sample sizes. A second goal of this paper is to discuss how to choose these parameters according to different criteria including the optimization of frequentist properties of posterior means.     

On predictive distributions and Bayesian networks

In this paper we are interested in discrete prediction problems for a decision-theoretic setting, where the task is to compute the predictive distribution for a finite set of possible alternatives. This question is first addressed in a general Bayesian framework, where we consider a set of probability distributions defined by some parametric model class. Given a prior distribution on the model parameters and a set of sample data, one possible approach for determining a predictive distribution is to fix the parameters to the instantiation with the maximum a posteriori probability. A more accurate predictive distribution can be obtained by computing the evidence (marginal likelihood), i.e., the integral over all the individual parameter instantiations. As an alternative to these two approaches, we demonstrate how to use Rissanen's new definition of stochastic complexity for determining predictive distributions, and show how the evidence predictive distribution with Jeffrey's prior approaches the new stochastic complexity predictive distribution in the limit with increasing amount of sample data. To compare the alternative approaches in practice, each of the predictive distributions discussed is instantiated in the Bayesian network model family case. In particular, to determine Jeffrey's prior for this model family, we show how to compute the (expected) Fisher information matrix for a fixed but arbitrary Bayesian network structure. In the empirical part of the paper the predictive distributions are compared by using the simple tree-structured Naive Bayes model, which is used in the experiments for computational reasons. The experimentation with several public domain classification datasets suggest that the evidence approach produces the most accurate predictions in the log-score sense. The evidence-based methods are also quite robust in the sense that they predict surprisingly well even when only a small fraction of the full training set is used.     

A natural lead-in approach to response-adaptive allocation for continuous outcomes

Response-adaptive (RA) allocation designs can skew the allocation of incoming subjects toward the better performing treatment group based on the previously accrued responses. While unstable estimators and increased variability can adversely affect adaptation in early trial stages, Bayesian methods can be implemented with decreasingly informative priors (DIP) to overcome these difficulties. DIPs have been previously used for binary outcomes to constrain adaptation early in the trial, yet gradually increase adaptation as subjects accrue. We extend the DIP approach to RA designs for continuous outcomes, primarily in the normal conjugate family by functionalizing the prior effective sample size to equal the unobserved sample size. We compare this effective sample size DIP approach to other DIP formulations. Further, we considered various allocation equations and assessed their behavior utilizing DIPs. Simulated clinical trials comparing the behavior of these approaches with traditional Frequentist and Bayesian RA as well as balanced designs show that the natural lead-in approaches maintain improved treatment with lower variability and greater power.     

Objective Bayesian multiple comparisons for normal variances

This paper considers the multiple comparisons problem for normal variances. We propose a solution based on a Bayesian model selection procedure to this problem in which no subjective input is considered. We construct the intrinsic and fractional priors for which the Bayes factors and model selection probabilities are well defined. The posterior probability of each model is used as a model selection tool. The behaviour of these Bayes factors is compared with the Bayesian information criterion of Schwarz and some frequentist tests.     

A Bayesian cluster analysis of election results

A Bayesian cluster analysis for the results of an election based on multinomial mixture models is proposed. The number of clusters is chosen based on the careful comparison of the results with predictive simulations from the models, and by checking whether models capture most of the spatial dependence in the results. By implementing the analysis on five recent elections in Barcelona, the reader is walked through the choice of the best statistics and graphical displays to help chose a model and present the results. Even though the models do not use any information about the location of the areas in which the results are broken into, in the example they uncover a four-cluster structure with a strong spatial dependence, that is very stable over time and relates to the demographic composition.     

On Bayesian estimators in multistage binomial designs

A new class of Bayesian estimators for a proportion in multistage binomial designs is considered. Priors belong to the beta-J distribution family, which is derived from the Fisher information associated with the design. The transposition of the beta parameters of the Haldane and the uniform priors in fixed binomial experiments into the beta-J distribution yields bias-corrected versions of these priors in multistage designs. We show that the estimator of the posterior mean based on the corrected Haldane prior and the estimator of the posterior mode based on the corrected uniform prior have good frequentist properties. An easy-to-use approximation of the estimator of the posterior mode is provided. The new Bayesian estimators are compared to Whitehead's and the uniformly minimum variance estimators through several multistage designs. Last, the bias of the estimator of the posterior mode is derived for a particular case.     

On the estimation problem of periodic autoregressive time series: symmetric and asymmetric innovations

Periodic autoregressive (PAR) models with symmetric innovations are widely used on time series analysis, whereas its asymmetric counterpart inference remains a challenge, because of a number of problems related to the existing computational methods. In this paper, we use an interesting relationship between periodic autoregressive and vector autoregressive (VAR) models to study maximum likelihood and Bayesian approaches to the inference of a PAR model with normal and skew-normal innovations, where different kinds of estimation methods for the unknown parameters are examined. Several technical difficulties which are usually complicated to handle are reported. Results are compared with the existing classical solutions and the practical implementations of the proposed algorithms are illustrated via comprehensive simulation studies. The methods developed in the study are applied and illustrate a real-time series. The Bayes factor is also used to compare the multivariate normal model versus the multivariate skew-normal model.