Empirical Bayes models of Poisson clinical trials and sample size determination

Bayesian methods are often used to reduce the sample sizes and/or increase the power of clinical trials. The right choice of the prior distribution is a critical step in Bayesian modeling. If the prior not completely specified, historical data may be used to estimate it. In the empirical Bayesian analysis, the resulting prior can be used to produce the posterior distribution. In this paper, we describe a Bayesian Poisson model with a conjugate Gamma prior. The parameters of Gamma distribution are estimated in the empirical Bayesian framework under two estimation schemes. The straightforward numerical search for the maximum likelihood (ML) solution using the marginal negative binomial distribution is unfeasible occasionally. We propose a simplification to the maximization procedure. The Markov Chain Monte Carlo method is used to create a set of Poisson parameters from the historical count data. These Poisson parameters are used to uniquely define the Gamma likelihood function. Easily computable approximation formulae may be used to find the ML estimations for the parameters of gamma distribution. For the sample size calculations, the ML solution is replaced by its upper confidence limit to reflect an incomplete exchangeability of historical trials as opposed to current studies. The exchangeability is measured by the confidence interval for the historical rate of the events. With this prior, the formula for the sample size calculation is completely defined. Published in 2009 by John Wiley & Sons, Ltd.     

Estimation of the scale parameter of the Rayleigh distribution with multiply type–II censored sample

Based on a multiply type-II censored sample, the maximum likelihood estimator (MLE) and Bayes estimator for the scale parameter and the reliability function of the Rayleigh distribution are derived. However, since the MLE does not exist an explicit form, an approximate MLE which is the maximizer of an approximate likelihood function will be given. The comparisons among estimators are investigated through Monte Carlo simulations. An illustrative example with the real data concerning the 23 ball bearing in the life test is presented.     

Estimation of the scale parameter of the half-logistic distribution under progressively type II censored sample

Based on a progressively type II censored sample, the maximum likelihood and Bayes estimators of the scale parameter of the half-logistic distribution are derived. However, since the maximum likelihood estimator (MLE) and Bayes estimator do not exist in an explicit form for the scale parameter, we consider a simple method of deriving an explicit estimator by approximating the likelihood function and derive the asymptotic variances of MLE and approximate MLE. Also, an approximation based on the Laplace approximation (Tierney and Kadane in J Am Stat Assoc 81:82–86, 1986) and importance sampling methods are used for obtaining the Bayes estimator. In order to compare the performance of the MLE, approximate MLE and Bayes estimates of the scale parameter, we use Monte Carlo simulation.     

Confidence Intervals for Current Status Data

Abstract.  The likelihood ratio statistic for testing pointwise hypotheses about the survival time distribution in the current status model can be inverted to yield confidence intervals (CIs). One advantage of this procedure is that CIs can be formed without estimating the unknown parameters that figure in the asymptotic distribution of the maximum likelihood estimator (MLE) of the distribution function. We discuss the likelihood ratio-based CIs for the distribution function and the quantile function and compare these intervals to several different intervals based on the MLE. The quantiles of the limiting distribution of the MLE are estimated using various methods including parametric fitting, kernel smoothing and subsampling techniques. Comparisons are carried out both for simulated data and on a data set involving time to immunization against rubella. The comparisons indicate that the likelihood ratio-based intervals are preferable from several perspectives.     

Likelihood methods in randomized trials with noncompliance and subsequent nonresponse

This article considers likelihood methods for estimating the causal effect of treatment assignment for a two-armed randomized trial assuming all-or-none treatment noncompliance and allowing for subsequent nonresponse. We first derive the observed data likelihood function as a closed form expression of the parameter given the observed data where both response and compliance state are treated as variables with missing values. Then we describe an iterative procedure which maximizes the observed data likelihood function directly to compute a maximum likelihood estimator (MLE) of the causal effect of treatment assignment. Closed form expressions at each iterative step are provided. Finally we compare the MLE with an alternative estimator where the probability distribution of the compliance state is estimated independent of the response and its missingness mechanism. Our work indicates that direct maximum likelihood inference is straightforward for this problem. Extensive simulation studies are provided to examine the finite sample performance of the proposed methods.     

Monte Carlo approximation of likelihood function in spatial GLMMs through an empirical Bayes method

In spatial generalized linear mixed models (SGLMMs), statistical inference encounters problems, since random effects in the model imply high-dimensional integrals to calculate the marginal likelihood function. In this article, we temporarily treat parameters as random variables and express the marginal likelihood function as a posterior expectation. Hence, the marginal likelihood function is approximated using the obtained samples from the posterior density of the latent variables and parameters given the data. However, in this setting, misspecification of prior distribution of correlation function parameter and problems associated with convergence of Markov chain Monte Carlo (MCMC) methods could have an unpleasant influence on the likelihood approximation. To avoid these challenges, we utilize an empirical Bayes approach to estimate prior hyperparameters. We also use a computationally efficient hybrid algorithm by combining inverse Bayes formula (IBF) and Gibbs sampler procedures. A simulation study is conducted to assess the performance of our method. Finally, we illustrate the method applying a dataset of standard penetration test of soil in an area in south of Iran.     

Estimation of the scale parameter of the Rayleigh distribution under general progressive censoring

Based on a general progressively type II censored sample, the maximum likelihood estimator (MLE), Bayes estimator under squared error loss and credible intervals for the scale parameter and the reliability function of the Rayleigh distribution are derived. Also, the Bayes predictive estimator and highest posterior density (HPD) prediction interval for future observation are considered. Comparisons among estimators are investigated through Monte Carlo simulations. An illustrative example with real data concerning 23 ball bearings in a life test is presented.     

Estimation of the scale parameter of the half-logistic distribution with multiply type II censored sample

In this paper, we consider the maximum likelihood and Bayes estimation of the scale parameter of the half-logistic distribution based on a multiply type II censored sample. However, the maximum likelihood estimator(MLE) and Bayes estimator do not exist in an explicit form for the scale parameter. We consider a simple method of deriving an explicit estimator by approximating the likelihood function and discuss the asymptotic variances of MLE and approximate MLE. Also, an approximation based on the Laplace approximation (Tierney & Kadane, 1986) is used to obtain the Bayes estimator. In order to compare the MLE, approximate MLE and Bayes estimates of the scale parameter, Monte Carlo simulation is used.     

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.     

Inference in flexible families of distributions with normal kernel

This paper addresses the inference problem for a flexible class of distributions with normal kernel known as skew-bimodal-normal family of distributions. We obtain posterior and predictive distributions assuming different prior specifications. We provide conditions for the existence of the maximum-likelihood estimators (MLE). An EM-type algorithm is built to compute them. As a by product, we obtain important results related to classical and Bayesian inferences for two special subclasses called bimodal-normal and skew-normal (SN) distribution families. We perform a Monte Carlo simulation study to analyse behaviour of the MLE and some Bayesian ones. Considering the frontier data previously studied in the literature, we use the skew-bimodal-normal (SBN) distribution for density estimation. For that data set, we conclude that the SBN model provides as good a fit as the one obtained using the location-scale SN model. Since the former is a more parsimonious model, such a result is shown to be more attractive.     

Kernel Density-Based Linear Regression Estimate

For linear regression models with non normally distributed errors, the least squares estimate (LSE) will lose some efficiency compared to the maximum likelihood estimate (MLE). In this article, we propose a kernel density-based regression estimate (KDRE) that is adaptive to the unknown error distribution. The key idea is to approximate the likelihood function by using a nonparametric kernel density estimate of the error density based on some initial parameter estimate. The proposed estimate is shown to be asymptotically as efficient as the oracle MLE which assumes the error density were known. In addition, we propose an EM type algorithm to maximize the estimated likelihood function and show that the KDRE can be considered as an iterated weighted least squares estimate, which provides us some insights on the adaptiveness of KDRE to the unknown error distribution. Our Monte Carlo simulation studies show that, while comparable to the traditional LSE for normal errors, the proposed estimation procedure can have substantial efficiency gain for non normal errors. Moreover, the efficiency gain can be achieved even for a small sample size.     

On maximum likelihood estimation of the long-memory parameter in fractional Gaussian noise

Approximate normality and unbiasedness of the maximum likelihood estimate (MLE) of the long-memory parameter H of a fractional Brownian motion hold reasonably well for sample sizes as small as 20 if the mean and scale parameter are known. We show in a Monte Carlo study that if the latter two parameters are unknown the bias and variance of the MLE of H both increase substantially. We also show that the bias can be reduced by using a parametric bootstrap procedure. In very large samples, maximum likelihood estimation becomes problematic because of the large dimension of the covariance matrix that must be inverted. To overcome this difficulty, we propose a maximum likelihood method based upon first differences of the data. These first differences form a short-memory process. We split the data into a number of contiguous blocks consisting of a relatively small number of observations. Computation of the likelihood function in a block then presents no computational problem. We form a pseudo-likelihood function consisting of the product of the likelihood functions in each of the blocks and provide a formula for the standard error of the resulting estimator of H. This formula is shown in a Monte Carlo study to provide a good approximation to the true standard error. The computation time required to obtain the estimate and its standard error from large data sets is an order of magnitude less than that required to obtain the widely used Whittle estimator. Application of the methodology is illustrated on two data sets.     

AN ALTERNATIVE PARAMETRIC APPROACH FOR DISCRETE MISSING DATA PROBLEMS

We propose an iterative method of estimation for discrete missing data problems that is conceptually different from the Expectation–Maximization (EM) algorithm and that does not in general yield the observed data maximum likelihood estimate (MLE). The proposed approach is based conceptually upon weighting the set of possible complete-data MLEs. Its implementation avoids the expectation step of EM, which can sometimes be problematic. In the simple case of Bernoulli trials missing completely at random, the iterations of the proposed algorithm are equivalent to the EM iterations. For a familiar genetics-oriented multinomial problem with missing count data and for the motivating example with epidemiologic applications that involves a mixture of a left censored normal distribution with a point mass at zero, we investigate the finite sample performance of the proposed estimator and find it to be competitive with that of the MLE. We give some intuitive justification for the method, and we explore an interesting connection between our algorithm and multiple imputation in order to suggest an approach for estimating standard errors.     

Bayes estimation and prediction of the two-parameter gamma distribution

In this article, the Bayes estimates of two-parameter gamma distribution are considered. It is well known that the Bayes estimators of the two-parameter gamma distribution do not have compact form. In this paper, it is assumed that the scale parameter has a gamma prior and the shape parameter has any log-concave prior, and they are independently distributed. Under the above priors, we use Gibbs sampling technique to generate samples from the posterior density function. Based on the generated samples, we can compute the Bayes estimates of the unknown parameters and can also construct HPD credible intervals. We also compute the approximate Bayes estimates using Lindley's approximation under the assumption of gamma priors of the shape parameter. Monte Carlo simulations are performed to compare the performances of the Bayes estimators with the classical estimators. One data analysis is performed for illustrative purposes. We further discuss the Bayesian prediction of future observation based on the observed sample and it is seen that the Gibbs sampling technique can be used quite effectively for estimating the posterior predictive density and also for constructing predictive intervals of the order statistics from the future sample.     

The Minimum Density Power Divergence Estimation for the Lognormal Density

In this article, we implement the minimum density power divergence estimation for estimating the parameters of the lognormal density. We compare the minimum density power divergence estimator (MDPDE) and the maximum likelihood estimator (MLE) in terms of robustness and asymptotic distribution. The simulations and an example indicate that the MDPDE is less biased than MLE and is as good as MLE in terms of the mean square error under various distributional situations.     

Non-parametric Bayesian analysis of clustered survival data

Clustered survival data are often modelled with frailty models which incorporate frailties to model the cluster specific heterogeneity and the dependence between observations in the same cluster. For the analysis of the frailty models, we propose Bayesian modelling with beta process prior on the cumulative hazard function and describe the details of the posterior computation. We demonstrate the method with two data sets using three different frailty distributions: gamma, log-normal and log-logistic distributions. We also empirically demonstrate the difficulty in checking the assumed frailty distribution with the posterior sample of the frailties.     

Approximate estimation in nonlinear panel data models

This paper is concerned with the estimation of a general class of nonlinear panel data models in which the conditional distribution of the dependent variable and the distribution of the heterogeneity factors are arbitrary. In general, exact analytical results for this problem do not exist. Here, Laplace and small-sigma appriximations for the marginal likelihood are presented. The computation of the MLE from both approximations is straightforward. It is shown that the accuracy of the Laplace approximation depends on both the sample size and the variance of the individual effects, whereas the accuracy of the small-sigma approximation is 0(1) with respect to the sample size. The results are applied to count, duration and probit panel data models. The accuracy of the approximations is evaluated through a Monte Carlo simulation experiment. The approximations are also applied in an analysis of youth unemployment in Australia.     

A stochastic approximation algorithm for maximum-likelihood estimation with incomplete data

We propose a new stochastic approximation (SA) algorithm for maximum-likelihood estimation (MLE) in the incomplete-data setting. This algorithm is most useful for problems when the EM algorithm is not possible due to an intractable E-step or M-step. Compared to other algorithm that have been proposed for intractable EM problems, such as the MCEM algorithm of Wei and Tanner (1990), our proposed algorithm appears more generally applicable and efficient. The approach we adopt is inspired by the Robbins-Monro (1951) stochastic approximation procedure, and we show that the proposed algorithm can be used to solve some of the long-standing problems in computing an MLE with incomplete data. We prove that in general O(n) simulation steps are required in computing the MLE with the SA algorithm and O(n log n) simulation steps are required in computing the MLE using the MCEM and/or the MCNR algorithm, where n is the sample size of the observations. Examples include computing the MLE in the nonlinear error-in-variable model and nonlinear regression model with random effects.     

Semi-parametric modelling and likelihood estimation with estimating equations

This paper proposes a semi-parametric modelling and estimating method for analysing censored survival data. The proposed method uses the empirical likelihood function to describe the information in data, and formulates estimating equations to incorporate knowledge of the underlying distribution and regression structure. The method is more flexible than the traditional methods such as the parametric maximum likelihood estimation (MLE), Cox's (1972) proportional hazards model, accelerated life test model, quasi-likelihood (Wedderburn, 1974) and generalized estimating equations (Liang & Zeger, 1986). This paper shows the existence and uniqueness of the proposed semi-parametric maximum likelihood estimates (SMLE) with estimating equations. The method is validated with known cases studied in the literature. Several finite sample simulation and large sample efficiency studies indicate that when the sample size is larger than 100 the SMLE is compatible with the parametric MLE; and in all case studies, the SMLE is about 15% better than the parametric MLE with a mis-specified underlying distribution.     

Zero-inflated models and estimation in zero-inflated Poisson distribution

In this paper, we briefly overview different zero-inflated probability distributions. We compare the performance of the estimates of Poisson, Generalized Poisson, ZIP, ZIGP and ZINB models through Mean square error (MSE), bias and Standard error (SE) when the samples are generated from ZIP distribution. We propose a new estimator referred to as probability estimator (PE) of inflation parameter of ZIP distribution based on moment estimator (ME) of the mean parameter and compare its performance with ME and maximum likelihood estimator (MLE) through a simulation study. We use the PE along with ME and MLE to fit ZIP distribution to various zero-inflated datasets and observe that the results do not differ significantly. We recommend using PE in place of MLE since it is easy to calculate and the simulation study in this paper demonstrates that the PE performs as good as MLE irrespective of the sample size.