A note on fiducial model averaging as an alternative to checking Bayesian and frequentist models

Just as frequentist hypothesis tests have been developed to check model assumptions, prior predictive p-values and other Bayesian p-values check prior distributions as well as other model assumptions. These model checks not only suffer from the usual threshold dependence of p-values, but also from the suppression of model uncertainty in subsequent inference. One solution is to transform Bayesian and frequentist p-values for model assessment into a fiducial distribution across the models. Averaging the Bayesian or frequentist posterior distributions with respect to the fiducial distribution can reproduce results from Bayesian model averaging or classical fiducial inference.     

A generalization of Jeffreys' rule for non regular models

ABSTRACT

We propose a generalization of the one-dimensional Jeffreys' rule in order to obtain non informative prior distributions for non regular models, taking into account the comments made by Jeffreys in his article of 1946. These non informatives are parameterization invariant and the Bayesian intervals have good behavior in frequentist inference. In some important cases, we can generate non informative distributions for multi-parameter models with non regular parameters. In non regular models, the Bayesian method offers a satisfactory solution to the inference problem and also avoids the problem that the maximum likelihood estimator has with these models. Finally, we obtain non informative distributions in job-search and deterministic frontier production homogenous models.     

Bayesian analysis of elapsed times in continuous‐time Markov chains

The authors consider Bayesian analysis for continuous‐time Markov chain models based on a conditional reference prior. For such models, inference of the elapsed time between chain observations depends heavily on the rate of decay of the prior as the elapsed time increases. Moreover, improper priors on the elapsed time may lead to improper posterior distributions. In addition, an infinitesimal rate matrix also characterizes this class of models. Experts often have good prior knowledge about the parameters of this matrix. The authors show that the use of a proper prior for the rate matrix parameters together with the conditional reference prior for the elapsed time yields a proper posterior distribution. The authors also demonstrate that, when compared to analyses based on priors previously proposed in the literature, a Bayesian analysis on the elapsed time based on the conditional reference prior possesses better frequentist properties. The type of prior thus represents a better default prior choice for estimation software.     

Bayesian analysis of bivariate competing risks models with covariates

Bivariate exponential models have often been used for the analysis of competing risks data involving two correlated risk components. Competing risks data consist only of the time to failure and cause of failure. In situations where there is positive probability of simultaneous failure, possibly the most widely used model is the Marshall–Olkin (J. Amer. Statist. Assoc. 62 (1967) 30) bivariate lifetime model. This distribution is not absolutely continuous as it involves a singularity component. However, the likelihood function based on the competing risks data is then identifiable, and any inference, Bayesian or frequentist, can be carried out in a straightforward manner. For the analysis of absolutely continuous bivariate exponential models, standard approaches often run into difficulty due to the lack of a fully identifiable likelihood (Basu and Ghosh; Commun. Statist. Theory Methods 9 (1980) 1515). To overcome the nonidentifiability, the usual frequentist approach is based on an integrated likelihood. Such an approach is implicit in Wada et al. (Calcutta Statist. Assoc. Bull. 46 (1996) 197) who proved some related asymptotic results. We offer in this paper an alternative Bayesian approach. Since systematic prior elicitation is often difficult, the present study focuses on Bayesian analysis with noninformative priors. It turns out that with an appropriate reparameterization, standard noninformative priors such as Jeffreys’ prior and its variants can be applied directly even though the likelihood is not fully identifiable. Two noninformative priors are developed that consist of Laplace's prior for nonidentifiable parameters and Laplace's and Jeffreys's priors for identifiable parameters. The resulting Bayesian procedures possess some frequentist optimality properties as well. Finally, these Bayesian methods are illustrated with analyses of a data set originating out of a lung cancer clinical trial conducted by the Eastern Cooperative Oncology Group.     

A dynamic power prior for borrowing historical data in noninferiority trials with binary endpoint

Traditionally, noninferiority hypotheses have been tested using a frequentist method with a fixed margin. Given that information for the control group is often available from previous studies, it is interesting to consider a Bayesian approach in which information is “borrowed” for the control group to improve efficiency. However, construction of an appropriate informative prior can be challenging. In this paper, we consider a hybrid Bayesian approach for testing noninferiority hypotheses in studies with a binary endpoint. To account for heterogeneity between the historical information and the current trial for the control group, a dynamic P value–based power prior parameter is proposed to adjust the amount of information borrowed from the historical data. This approach extends the simple test‐then‐pool method to allow a continuous discounting power parameter. An adjusted α level is also proposed to better control the type I error. Simulations are conducted to investigate the performance of the proposed method and to make comparisons with other methods including test‐then‐pool and hierarchical modeling. The methods are illustrated with data from vaccine clinical trials.     

Laplace approximations for censored linear regression models

We consider approximate Bayesian inference about scalar parameters of linear regression models with possible censoring. A second-order expansion of their Laplace posterior is seen to have a simple and intuitive form for logconcave error densities with nondecreasing hazard functions. The accuracy of the approximations is assessed for normal and Gumbel errors when the number of regressors increases with sample size. Perturbations of the prior and the likelihood are seen to be easily accommodated within our framework. Links with the work of DiCiccio et al. (1990) and Viveros and Sprott (1987) extend the applicability of our results to conditional frequentist inference based on likelihood-ratio statistics.     

Inference and Decision Making for 21st-Century Drug Development and Approval

ABSTRACT

The cost and time of pharmaceutical drug development continue to grow at rates that many say are unsustainable. These trends have enormous impact on what treatments get to patients, when they get them and how they are used. The statistical framework for supporting decisions in regulated clinical development of new medicines has followed a traditional path of frequentist methodology. Trials using hypothesis tests of “no treatment effect” are done routinely, and the p-value < 0.05 is often the determinant of what constitutes a “successful” trial. Many drugs fail in clinical development, adding to the cost of new medicines, and some evidence points blame at the deficiencies of the frequentist paradigm. An unknown number effective medicines may have been abandoned because trials were declared “unsuccessful” due to a p-value exceeding 0.05. Recently, the Bayesian paradigm has shown utility in the clinical drug development process for its probability-based inference. We argue for a Bayesian approach that employs data from other trials as a “prior” for Phase 3 trials so that synthesized evidence across trials can be utilized to compute probability statements that are valuable for understanding the magnitude of treatment effect. Such a Bayesian paradigm provides a promising framework for improving statistical inference and regulatory decision making.     

A Simple Analysis of the Exact Probability Matching Prior in the Location-Scale Model

It has long been asserted that in univariate location-scale models, when concerned with inference for either the location or scale parameter, the use of the inverse of the scale parameter as a Bayesian prior yields posterior credible sets that have exactly the correct frequentist confidence set interpretation. This claim dates to at least Peers, and has subsequently been noted by various authors, with varying degrees of justification. We present a simple, direct demonstration of the exact matching property of the posterior credible sets derived under use of this prior in the univariate location-scale model. This is done by establishing an equivalence between the conditional frequentist and posterior densities of the pivotal quantities on which conditional frequentist inferences are based.     

Testing equality of regression coefficients in heteroscedastic normal regression models

This article addresses the problem of testing whether the vectors of regression coefficients are equal for two independent normal regression models when the error variances are unknown. This problem poses severe difficulties both to the frequentist and Bayesian approaches to statistical inference. In the former approach, normal hypothesis testing theory does not apply because of the unrelated variances. In the latter, the prior distributions typically used for the parameters are improper and hence the Bayes factor-based solution cannot be used.We propose a Bayesian solution to this problem in which no subjective input is considered. We first generate “objective” proper prior distributions (intrinsic priors) for which the Bayes factor and model posterior probabilities are well defined. The posterior probability of each model is used as a model selection tool. This consistent procedure of testing hypotheses is compared with some of the frequentist approximate tests proposed in the literature.     

A Bayesian approach for estimating antiviral efficacy in HIV dynamic models

The study of HIV dynamics is one of the most important developments in recent AIDS research. It has led to a new understanding of the pathogenesis of HIV infection. Although important findings in HIV dynamics have been published in prestigious scientific journals, the statistical methods for parameter estimation and model-fitting used in those papers appear surprisingly crude and have not been studied in more detail. For example, the unidentifiable parameters were simply imputed by mean estimates from previous studies, and important pharmacological/clinical factors were not considered in the modelling. In this paper, a viral dynamic model is developed to evaluate the effect of pharmacokinetic variation, drug resistance and adherence on antiviral responses. In the context of this model, we investigate a Bayesian modelling approach under a non-linear mixed-effects (NLME) model framework. In particular, our modelling strategy allows us to estimate time-varying antiviral efficacy of a regimen during the whole course of a treatment period by incorporating the information of drug exposure and drug susceptibility. Both simulated and real clinical data examples are given to illustrate the proposed approach. The Bayesian approach has great potential to be used in many aspects of viral dynamics modelling since it allow us to fit complex dynamic models and identify all the model parameters. Our results suggest that Bayesian approach for estimating parameters in HIV dynamic models is flexible and powerful.     

Longitudinal data analysis using Bayesian-frequentist hybrid random effects model

The mixed random effect model is commonly used in longitudinal data analysis within either frequentist or Bayesian framework. Here we consider a case, in which we have prior knowledge on partial parameters, while no such information on the rest of the parameters. Thus, we use the hybrid approach on the random-effects model with partial parameters. The parameters are estimated via Bayesian procedure, and the rest of parameters by the frequentist maximum likelihood estimation (MLE), simultaneously on the same model. In practice, we often know partial prior information such as, covariates of age, gender, etc. These information can be used, and accurate estimations in mixed random-effects model can be obtained. A series of simulation studies were performed to compare the results with the commonly used random-effects model with and without partial prior information. The results in hybrid estimation (HYB) and MLE were very close to each other. The estimated θ values in with partial prior information model (HYB) were more closer to true θ values, and showed less variances than without partial prior information in MLE. To compare with true θ values, the mean square of errors are much less in HYB than in MLE. This advantage of HYB is very obvious in longitudinal data with a small sample size. The methods of HYB and MLE are applied to a real longitudinal data for illustration purposes.     

Jointly modeling time-to-event and longitudinal data: a Bayesian approach

This article explores Bayesian joint models of event times and longitudinal measures with an attempt to overcome departures from normality of the longitudinal response, measurement errors, and shortages of confidence in specifying a parametric time-to-event model. We allow the longitudinal response to have a skew distribution in the presence of measurement errors, and assume the time-to-event variable to have a nonparametric prior distribution. Posterior distributions of the parameters are attained simultaneously for inference based on Bayesian approach. An example from a recent AIDS clinical trial illustrates the methodology by jointly modeling the viral dynamics and the time to decrease in CD4/CD8 ratio in the presence of CD4 counts with measurement errors to compare potential models with various scenarios and different distribution specifications. The analysis outcome indicates that the time-varying CD4 covariate is closely related to the first-phase viral decay rate, but the time to CD4/CD8 decrease is not highly associated with either the two viral decay rates or the CD4 changing rate over time. These findings may provide some quantitative guidance to better understand the relationship of the virological and immunological responses to antiretroviral treatments.     

Bayesian analysis of mixture modelling using the multivariate t distribution

A finite mixture model using the multivariate t distribution has been shown as a robust extension of normal mixtures. In this paper, we present a Bayesian approach for inference about parameters of t-mixture models. The specifications of prior distributions are weakly informative to avoid causing nonintegrable posterior distributions. We present two efficient EM-type algorithms for computing the joint posterior mode with the observed data and an incomplete future vector as the sample. Markov chain Monte Carlo sampling schemes are also developed to obtain the target posterior distribution of parameters. The advantages of Bayesian approach over the maximum likelihood method are demonstrated via a set of real data.     

A Bayesian Approach to Model Interdependent Event Histories by Graphical Models

In event history analysis, the problem of modeling two interdependent processes is still not completely solved. In a frequentist framework, there are two most general approaches: the causal approach and the system approach. The recent growing interest in Bayesian statistics suggests some interesting works on survival models and event history analysis in a Bayesian perspective. In this work we present a possible solution for the analysis of dynamic interdependence by a Bayesian perspective in a graphical duration model framework, using marked point processes. Main results from the Bayesian approach and the comparison with the frequentist one are illustrated on a real example: the analysis of the dynamic relationship between fertility and female employment.     

Identifiable state‐space models: A case study of the Bay of Fundy sea scallop fishery

State‐space models (SSMs) are now popular tools in fisheries science for providing management advice when faced with noisy survey and commercial fishery data. Such models are often fitted within a Bayesian framework requiring both the specification of prior distributions for model parameters and simulation‐based approaches for inference. Here we present a frequentist framework as a viable alternative and recommend using the Laplace approximation with automatic differentiation, as implemented in the R package Template Model Builder, for fast fitting and reliable inference. Additionally we highlight some identifiability issues associated with SSMs that fisheries scientists should be aware of and demonstrate how our modelling strategy surmounts these problems. Using the Bay of Fundy sea scallop fishery we show that our implementation yields more conservative advice than that of the reference model. The Canadian Journal of Statistics 47: 27–45; 2019 © 2018 Statistical Society of Canada     

Bayesian quantile regression for single-index models

Using an asymmetric Laplace distribution, which provides a mechanism for Bayesian inference of quantile regression models, we develop a fully Bayesian approach to fitting single-index models in conditional quantile regression. In this work, we use a Gaussian process prior for the unknown nonparametric link function and a Laplace distribution on the index vector, with the latter motivated by the recent popularity of the Bayesian lasso idea. We design a Markov chain Monte Carlo algorithm for posterior inference. Careful consideration of the singularity of the kernel matrix, and tractability of some of the full conditional distributions leads to a partially collapsed approach where the nonparametric link function is integrated out in some of the sampling steps. Our simulations demonstrate the superior performance of the Bayesian method versus the frequentist approach. The method is further illustrated by an application to the hurricane data.     

A matching prior based on the modified profile likelihood in a generalized Weibull stress‐strength model

Bayesian inference of a generalized Weibull stress‐strength model (SSM) with more than one strength component is considered. For this problem, properly assigning priors for the reliabilities is challenging due to the presence of nuisance parameters. Matching priors, which are priors matching the posterior probabilities of certain regions with their frequentist coverage probabilities, are commonly used but difficult to derive in this problem. Instead, we apply an alternative method and derive a matching prior based on a modification of the profile likelihood. Simulation studies show that this proposed prior performs well in terms of frequentist coverage and estimation even when the sample sizes are minimal. The prior is applied to two real datasets. The Canadian Journal of Statistics 41: 83–97; 2013 © 2012 Statistical Society of Canada     

The Bayesian and frequentist approaches to testing a one-sided hypothesis about a multivariate mean

This paper compares the Bayesian and frequentist approaches to testing a one-sided hypothesis about a multivariate mean. First, this paper proposes a simple way to assign a Bayesian posterior probability to one-sided hypotheses about a multivariate mean. The approach is to use (almost) the exact posterior probability under the assumption that the data has multivariate normal distribution, under either a conjugate prior in large samples or under a vague Jeffreys prior. This is also approximately the Bayesian posterior probability of the hypothesis based on a suitably flat Dirichlet process prior over an unknown distribution generating the data. Then, the Bayesian approach and a frequentist approach to testing the one-sided hypothesis are compared, with results that show a major difference between Bayesian reasoning and frequentist reasoning. The Bayesian posterior probability can be substantially smaller than the frequentist p-value. A class of example is given where the Bayesian posterior probability is basically 0, while the frequentist p-value is basically 1. The Bayesian posterior probability in these examples seems to be more reasonable. Other drawbacks of the frequentist p-value as a measure of whether the one-sided hypothesis is true are also discussed.     

Generalized Inference for a Class of Linear Models Under Heteroscedasticity

In this article we study inferences for a class of linear models under heteroscedasticity. Using the generalized inference approach, we obtain the generalized p-values of two-sided hypotheses for the multi-dimensional location parameters and one-sided hypotheses for the scale parameters, respectively. Some frequentist properties in small-sample cases and large-sample cases are proven.