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.     

Fully Bayesian logistic regression with hyper-LASSO priors for high-dimensional feature selection

Feature selection arises in many areas of modern science. For example, in genomic research, we want to find the genes that can be used to separate tissues of different classes (e.g. cancer and normal). One approach is to fit regression/classification models with certain penalization. In the past decade, hyper-LASSO penalization (priors) have received increasing attention in the literature. However, fully Bayesian methods that use Markov chain Monte Carlo (MCMC) for regression/classification with hyper-LASSO priors are still in lack of development. In this paper, we introduce an MCMC method for learning multinomial logistic regression with hyper-LASSO priors. Our MCMC algorithm uses Hamiltonian Monte Carlo in a restricted Gibbs sampling framework. We have used simulation studies and real data to demonstrate the superior performance of hyper-LASSO priors compared to LASSO, and to investigate the issues of choosing heaviness and scale of hyper-LASSO priors.     

Approximate reference priors for Gaussian random fields

Reference priors are theoretically attractive for the analysis of geostatistical data since they enable automatic Bayesian analysis and have desirable Bayesian and frequentist properties. But their use is hindered by computational hurdles that make their application in practice challenging. In this work, we derive a new class of default priors that approximate reference priors for the parameters of some Gaussian random fields. It is based on an approximation to the integrated likelihood of the covariance parameters derived from the spectral approximation of stationary random fields. This prior depends on the structure of the mean function and the spectral density of the model evaluated at a set of spectral points associated with an auxiliary regular grid. In addition to preserving the desirable Bayesian and frequentist properties, these approximate reference priors are more stable, and their computations are much less onerous than those of exact reference priors. Unlike exact reference priors, the marginal approximate reference prior of correlation parameter is always proper, regardless of the mean function or the smoothness of the correlation function. This property has important consequences for covariance model selection. An illustration comparing default Bayesian analyses is provided with a dataset of lead pollution in Galicia, Spain.     

Incorporating historical information to improve dose optimization design with toxicity and efficacy endpoints: iBOIN-ET

In modern oncology drug development, adaptive designs have been proposed to identify the recommended phase 2 dose. The conventional dose finding designs focus on the identification of maximum tolerated dose (MTD). However, designs ignoring efficacy could put patients under risk by pushing to the MTD. Especially in immuno-oncology and cell therapy, the complex dose-toxicity and dose-efficacy relationships make such MTD driven designs more questionable. Additionally, it is not uncommon to have data available from other studies that target on similar mechanism of action and patient population. Due to the high variability from phase I trial, it is beneficial to borrow historical study information into the design when available. This will help to increase the model efficiency and accuracy and provide dose specific recommendation rules to avoid toxic dose level and increase the chance of patient allocation at potential efficacious dose levels. In this paper, we propose iBOIN-ET design that uses prior distribution extracted from historical studies to minimize the probability of decision error. The proposed design utilizes the concept of skeleton from both toxicity and efficacy data, coupled with prior effective sample size to control the amount of historical information to be incorporated. Extensive simulation studies across a variety of realistic settings are reported including a comparison of iBOIN-ET design to other model based and assisted approaches. The proposed novel design demonstrates the superior performances in percentage of selecting the correct optimal dose (OD), average number of patients allocated to the correct OD, and overdosing control during dose escalation process.     

Prior distributions expressing ignorance about convex increasing failure rates

This paper deals with the specification of probability distributions expressing ignorance concerning annual or otherwise discretized failure or mortality rates, when these rates can safely be assumed to be increasing and convex, but are completely unknown otherwise. Such distributions can be used as noninformative priors for Bayesian analysis of failure data. We demonstrate why a uniform distribution used in earlier work is unsatisfactory, especially from the point of view of insensitivity with respect to the time scale that is chosen for the problem at hand. We suggest alternative distributions based on Dirichlet distributed weights for the extreme points of relevant convex sets, and discuss which consequences a requirement for scale neutrality has for the choice of Dirichlet parameters.     

Adaptively leveraging external data with robust meta-analytical-predictive prior using empirical Bayes

The robust meta-analytical-predictive (rMAP) prior is a popular method to robustly leverage external data. However, a mixture coefficient would need to be pre-specified based on the anticipated level of prior-data conflict. This can be very challenging at the study design stage. We propose a novel empirical Bayes robust MAP (EB-rMAP) prior to address this practical need and adaptively leverage external/historical data. Built on Box's prior predictive p-value, the EB-rMAP prior framework balances between model parsimony and flexibility through a tuning parameter. The proposed framework can be applied to binomial, normal, and time-to-event endpoints. Implementation of the EB-rMAP prior is also computationally efficient. Simulation results demonstrate that the EB-rMAP prior is robust in the presence of prior-data conflict while preserving statistical power. The proposed EB-rMAP prior is then applied to a clinical dataset that comprises 10 oncology clinical trials, including the prospective study.     

Sample size re-estimation in Phase 2 dose-finding: Conditional power versus Bayesian predictive power

Unblinded sample size re-estimation (SSR) is often planned in a clinical trial when there is large uncertainty about the true treatment effect. For Proof-of Concept (PoC) in a Phase II dose finding study, contrast test can be adopted to leverage information from all treatment groups. In this article, we propose two-stage SSR designs using frequentist conditional power (CP) and Bayesian predictive power (PP) for both single and multiple contrast tests. The Bayesian SSR can be implemented under a wide range of prior settings to incorporate different prior knowledge. Taking the adaptivity into account, all type I errors of final analysis in this paper are rigorously protected. Simulation studies are carried out to demonstrate the advantages of unblinded SSR in multi-arm trials.