The analysis of incontinence episodes and other count data in patients with overactive bladder by Poisson and negative binomial regression

Clinical studies in overactive bladder have traditionally used analysis of covariance or nonparametric methods to analyse the number of incontinence episodes and other count data. It is known that if the underlying distributional assumptions of a particular parametric method do not hold, an alternative parametric method may be more efficient than a nonparametric one, which makes no assumptions regarding the underlying distribution of the data. Therefore, there are advantages in using methods based on the Poisson distribution or extensions of that method, which incorporate specific features that provide a modelling framework for count data. One challenge with count data is overdispersion, but methods are available that can account for this through the introduction of random effect terms in the modelling, and it is this modelling framework that leads to the negative binomial distribution. These models can also provide clinicians with a clearer and more appropriate interpretation of treatment effects in terms of rate ratios. In this paper, the previously used parametric and non‐parametric approaches are contrasted with those based on Poisson regression and various extensions in trials evaluating solifenacin and mirabegron in patients with overactive bladder. In these applications, negative binomial models are seen to fit the data well. Copyright © 2014 John Wiley & Sons, Ltd.     

Bayesian approach to errors-in-variables in count data regression models with departures from normality and overdispersion

In most practical applications, the quality of count data is often compromised due to errors-in-variables (EIVs). In this paper, we apply Bayesian approach to reduce bias in estimating the parameters of count data regression models that have mismeasured independent variables. Furthermore, the exposure model is misspecified with a flexible distribution, hence our approach remains robust against any departures from normality in its true underlying exposure distribution. The proposed method is also useful in realistic situations as the variance of EIVs is estimated instead of assumed as known, in contrast with other methods of correcting bias especially in count data EIVs regression models. We conduct simulation studies on synthetic data sets using Markov chain Monte Carlo simulation techniques to investigate the performance of our approach. Our findings show that the flexible Bayesian approach is able to estimate the values of the true regression parameters consistently and accurately.     

A review of the CTP distribution: a comparison with other over- and underdispersed count data models

The complex triparametric Pearson (CTP) distribution is a flexible model belonging to the Gaussian hypergeometric family that can account for over- and underdispersion. However, despite its good properties, not much attention has been paid to it. So, we revive the CTP comparing it with some well-known distributions that cope with overdispersion (negative binomial, generalized Poisson and univariate generalized Waring) as well as underdispersion (Conway–Maxwell–Poisson (CMP) and hyper-Poisson (HP)). We make a simulation study that reveals the performance of the CTP and shows that it has its own space among count data models. In this sense, we also explore some overdispersed datasets which seem to be more appropriately modelled by the CTP than by other usual models. Moreover, we include two underdispersed examples to illustrate that the CTP can provide similar fits to the CMP or HP (sometimes even more accurate) without the computational problems of these models.     

Score tests for heterogeneity and overdispersion in zero‐inflated Poisson and binomial regression models

Hall (2000) has described zero‐inflated Poisson and binomial regression models that include random effects to account for excess zeros and additional sources of heterogeneity in the data. The authors of the present paper propose a general score test for the null hypothesis that variance components associated with these random effects are zero. For a zero‐inflated Poisson model with random intercept, the new test reduces to an alternative to the overdispersion test of Ridout, Demério & Hinde (2001). The authors also examine their general test in the special case of the zero‐inflated binomial model with random intercept and propose an overdispersion test in that context which is based on a beta‐binomial alternative.     

PoisNor: An R package for generation of multivariate data with Poisson and normal marginals

In this article, the operational details of the R package PoisNor that is designed for simulating multivariate data with count and continuous variables with a prespecified correlation matrix are described, and examples of some important functions are given. The data-generation mechanism is a combination of the “NORmal To Anything” principle and a recently established connection between Poisson and normal correlations. The package provides a unique and useful tool that has been lacking for generating multivariate mixed data with Poisson and normal components.     

A comparison of population average and random-effect models for the analysis of longitudinal count data with base-line information

The generalized estimating equation (GEE) approach to the analysis of longitudinal data has many attractive robustness properties and can provide a 'population average' characterization of interest, for example, to clinicians who have to treat patients on the basis of their observed characteristics. However, these methods have limitations which restrict their usefulness in both the social and the medical sciences. This conclusion is based on the premise that the main motivations for longitudinal analysis are insight into microlevel dynamics and improved control for omitted or unmeasured variables. We claim that to address these issues a properly formulated random-effects model is required. In addition to a theoretical assessment of some of the issues, we illustrate this by reanalysing data on polyp counts. In this example, the covariates include a base-line outcome, and the effectiveness of the treatment seems to vary by base-line. We compare the random-effects approach with the GEE approach and conclude that the GEE approach is inappropriate for assessing the treatment effects for these data.     

A simple test for the treatment effect in clinical trials with a sequential parallel comparison design and negative binomial outcomes

In placebo‐controlled, double‐blinded, randomized clinical trials, the presence of placebo responders reduces the effect size for comparison of the active drug group with the placebo group. An attempt to resolve this problem is to use the sequential parallel comparison design (SPCD). Although there are SPCDs with dichotomous or continuous outcomes, an SPCD with negative binomial outcomes—with which investigators deal eg, in clinical trials involving multiple sclerosis, where the investigators are still concerned about the presence of placebo responders—has not yet been discussed. In this article, we propose a simple test for the treatment effect in clinical trials with an SPCD and negative binomial outcomes. Through simulations, we show that the analysis method achieves the nominal type I error rate and power, whereas the sample size calculation provides the sample size with adequate power accuracy.     

A clustering approach to detect multiple outliers in linear functional relationship model for circular data

Outlier detection has been used extensively in data analysis to detect anomalous observation in data. It has important applications such as in fraud detection and robust analysis, among others. In this paper, we propose a method in detecting multiple outliers in linear functional relationship model for circular variables. Using the residual values of the Caires and Wyatt model, we applied the hierarchical clustering approach. With the use of a tree diagram, we illustrate the detection of outliers graphically. A Monte Carlo simulation study is done to verify the accuracy of the proposed method. Low probability of masking and swamping effects indicate the validity of the proposed approach. Also, the illustrations to two sets of real data are given to show its practical applicability.     

Sensitivity analysis of longitudinal count responses: a local influence approach and application to medical data

Longitudinal count responses are often analyzed with a Poisson mixed model. However, under overdispersion, these responses are better described by a negative binomial mixed model. Estimators of the corresponding parameters are usually obtained by the maximum likelihood method. To investigate the stability of these maximum likelihood estimators, we propose a methodology of sensitivity analysis using local influence. As count responses are discrete, we are unable to perturb them with the standard scheme used in local influence. Then, we consider an appropriate perturbation for the means of these responses. The proposed methodology is useful in different applications, but particularly when medical data are analyzed, because the removal of influential cases can change the statistical results and then the medical decision. We study the performance of the methodology by using Monte Carlo simulation and applied it to real medical data related to epilepsy and headache. All of these numerical studies show the good performance and potential of the proposed methodology.     

From grouped to de-grouped data: a new approach in distribution fitting for grouped data

Sampling within a given interval with a constraint has not been previously considered. Standard parametric simulation engines require knowledge of the parameters of the distribution from which a sample is drawn. These methods are limited if additional constrains are required for the simulated data. We propose a method that generates the targeted number of individual observations within a given interval with a constraint that the average value of observations is known. This method is further extended to a grouped data setting, as a way of data de-grouping, when the frequency and average value of observations are provided for each group. Several simulation studies are employed to evaluate the performance of the proposed method, in case of both a single interval and grouped data, for different simulation settings. Furthermore, the proposed method is evaluated in the parameter recovery when different distributions are fitted to the de-grouped data. This method is found to be superior to the uniform method previously used in data de-grouping. The results of the simulation study are promising and they show that this method can be used successfully in the applications where data de-grouping requires that the average value of observations is maintained in each group. The application of the proposed method is illustrated on a real data of insurance losses for bodily injury claims.     

An empirical Bayes approach to evaluation of results for a specific region in multiregional clinical trials

To accelerate the drug development process and shorten approval time, the design of multiregional clinical trials (MRCTs) incorporates subjects from many countries/regions around the world under the same protocol. After showing the overall efficacy of a drug in all global regions, one can also simultaneously evaluate the possibility of applying the overall trial results to all regions and subsequently support drug registration in each of them. In this paper, we focus on a specific region and establish a statistical criterion to assess the consistency between the specific region and overall results in an MRCT. More specifically, we treat each region in an MRCT as an independent clinical trial, and each perhaps has different treatment effect. We then construct the empirical prior information for the treatment effect for the specific region on the basis of all of the observed data from other regions. We will conclude similarity between the specific region and all regions if the posterior probability of deriving a positive treatment effect in the specific region is large, say 80%. Numerical examples illustrate applications of the proposed approach in different scenarios. Copyright © 2013 John Wiley & Sons, Ltd.     

A Bayesian approach for locating change points in a compound Poisson process with application to detecting DNA copy number variations

This work examines the problem of locating changes in the distribution of a Compound Poisson Process where the variables being summed are iid normal and the number of variable follows the Poisson distribution. A Bayesian approach is developed to identify the location of significant changes in any of the parameters of the distribution, and a sliding window algorithm is used to identify multiple change points. These results can be applied in any field of study where an interest in locating changes not only in the parameter of a normally distributed data set but also in the rate of their occurrence. It has direct application to the study of DNA copy number variations in cancer research, where it is known that the distances between the genes can affect their intensity level.     

Kernel partial correlation: a novel approach to capturing conditional independence in graphical models for noisy data

Graphical models capture the conditional independence structure among random variables via existence of edges among vertices. One way of inferring a graph is to identify zero partial correlation coefficients, which is an effective way of finding conditional independence under a multivariate Gaussian setting. For more general settings, we propose kernel partial correlation which extends partial correlation with a combination of two kernel methods. First, a nonparametric function estimation is employed to remove effects from other variables, and then the dependence between remaining random components is assessed through a nonparametric association measure. The proposed approach is not only flexible but also robust under high levels of noise owing to the robustness of the nonparametric approaches.     

An extensive power evaluation of a novel two-sample density-based empirical likelihood ratio test for paired data with an application to a treatment study of attention-deficit/hyperactivity disorder and severe mood dysregulation

In many case-control studies, it is common to utilize paired data when treatments are being evaluated. In this article, we propose and examine an efficient distribution-free test to compare two independent samples, where each is based on paired observations. We extend and modify the density-based empirical likelihood ratio test presented by Gurevich and Vexler [7] to formulate an appropriate parametric likelihood ratio test statistic corresponding to the hypothesis of our interest and then to approximate the test statistic nonparametrically. We conduct an extensive Monte Carlo study to evaluate the proposed test. The results of the performed simulation study demonstrate the robustness of the proposed test with respect to values of test parameters. Furthermore, an extensive power analysis via Monte Carlo simulations confirms that the proposed method outperforms the classical and general procedures in most cases related to a wide class of alternatives. An application to a real paired data study illustrates that the proposed test can be efficiently implemented in practice.