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.     

Utilizing Bayesian predictive power in clinical trial design

The Bayesian paradigm provides an ideal platform to update uncertainties and carry them over into the future in the presence of data. Bayesian predictive power (BPP) reflects our belief in the eventual success of a clinical trial to meet its goals. In this paper we derive mathematical expressions for the most common types of outcomes, to make the BPP accessible to practitioners, facilitate fast computations in adaptive trial design simulations that use interim futility monitoring, and propose an organized BPP-based phase II-to-phase III design framework.     

A Bayesian adaptive design for biosimilar trials with time-to-event endpoint

A biosimilar drug is a biological product that is highly similar to and at the same time has no clinically meaningful difference from licensed product in terms of safety, purity, and potency. Biosimilar study design is essential to demonstrate the equivalence between biosimilar drug and reference product. However, existing designs and assessment methods are primarily based on binary and continuous endpoints. We propose a Bayesian adaptive design for biosimilarity trials with time-to-event endpoint. The features of the proposed design are twofold. First, we employ the calibrated power prior to precisely borrow relevant information from historical data for the reference drug. Second, we propose a two-stage procedure using the Bayesian biosimilarity index (BBI) to allow early stop and improve the efficiency. Extensive simulations are conducted to demonstrate the operating characteristics of the proposed method in contrast with some naive method. Sensitivity analysis and extension with respect to the assumptions are presented.     

A Bayesian analysis of a change in the parameters of autoregressive time series

In this article, we consider a Bayesian analysis of a possible change in the parameters of autoregressive time series of known order p, AR(p). An unconditional Bayesian test based on highest posterior density (HPD) credible sets is determined. The test is useful to detect a change in any one of the parameters separately. Using the Gibbs sampler algorithm, we approximate the posterior densities of the change point and other parameters to calculate the p-values that define our test.     

Shared frailty model based on reversed hazard rate for left censored data

Frailty models are used in the survival analysis to account for the unobserved heterogeneity in the individual risks to disease and death. To analyze the bivariate data on related survival times (e.g., matched pairs experiments, twin or family data), the shared frailty models were suggested. In this article, we introduce the shared gamma frailty models with the reversed hazard rate. We develop the Bayesian estimation procedure using the Markov chain Monte Carlo (MCMC) technique to estimate the parameters involved in the model. We present a simulation study to compare the true values of the parameters with the estimated values. We apply the model to a real life bivariate survival dataset.     

Inferences on functions of Pareto parameters with application to income inequality measures

The Theil, Pietra, Éltetö and Frigyes measures of income inequality associated with the Pareto distribution function are expressed in terms of parameters defining the Pareto distribution. Inference procedures based on the generalized variable method, the large sample method, and the Bayesian method for testing of, and constructing confidence interval for, these measures are discussed. The results of Monte Carlo study are used to compare the performance of the suggested inference procedures from a population characterized by a Pareto distribution.     

Gibbs sampling for marginal posterior expectations

In earlier work (Gelfand and Smith, 1990 and Gelfand et al, 1990) a sampling based approach using the Gibbs sampler was offered as a means for developing marginal posterior densities for a wide range of Bayesian problems several of which were previously inaccessible. Our purpose here is two-fold. First we flesh out the implementation of this approach for calculation of arbitrary expectations of interest. Secondly we offer comparison with perhaps the most prominent approach for calculating posterior expectations, analytic approximation involving application of the LaPlace method. Several illustrative examples are discussed as well. Clear advantages for the sampling based approach emerge.     

Subjective priors for the dirichlet process

This paper reviews difficulties with the interpretation and use of the prior parameter u required in the Dirichlet approach to nonpararnetric Bayesian statistics. Two subjective prior distributions are introduced and studied. These priors are obtained computationally by requiring that the experimenter specify certain constraints.     

Bayesian analysis of a multiple-recapture model

In the Bayesian analysis of a multiple-recapture census, different diffuse prior distributions can lead to markedly different inferences about the population size N. Through consideration of the Fisher information matrix it is shown that the number of captures in each sample typically provides little information about N. This suggests that if there is no prior information about capture probabilities, then knowledge of just the sample sizes and not the number of recaptures should leave the distribution of Nunchanged. A prior model that has this property is identified and the posterior distribution is examined. In particular, asymptotic estimates of the posterior mean and variance are derived. Differences between Bayesian and classical point and interval estimators are illustrated through examples.     

Approximate maximum likelihood estimation in the presence of extra-poisson variation

A two-stage hierarchical model for analysis of discrete data with extra-Poisson variation is examined. The model consists of a Poisson distribution with a mixing lognormal distribution for the mean. A method of approximate maximum likelihood estimation of the parameters is proposed. The method uses the EM algorithm and approximations to facilitate its implementation are derived. Approximate standard errors of the estimates are provided and a numerical example is used to illustrate the method.