Use of copula to model within-study association in bivariate meta-analysis of binomial data at the aggregate level a Bayesian approach and application to surrogate endpoint evaluation
Tasos Papanikos, John R Thompson, Keith R Abrams, Sylwia Bujkiewicz
Bivariate meta-analysis provides a useful framework for combining information across related studies and has been utilised to combine evidence from clinical studies to evaluate treatment efficacy on two outcomes. It has also been used to investigate surrogacy patterns between treatment effects on the surrogate endpoint and the final outcome. Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final outcome and to predict clinical benefit or harm. The standard bivariate meta-analytic approach models the observed treatment effects on the surrogate and the final outcome outcomes jointly, at both the within-study and between-studies levels, using a bivariate normal distribution. For binomial data, a normal approximation on log odds ratio scale can be used. However, this method may lead to biased results when the proportions of events are close to one or zero, affecting the validation of surrogate endpoints. In this paper, we explore modelling the two outcomes on the original binomial scale. Firstly, we present a method that uses independent binomial likelihoods to model the within-study variability avoiding to approximate the observed treatment effects. However, the method ignores the within-study association. To overcome this issue, we propose a method using a bivariate copula with binomial marginals, which allows the model to account for the within-study association. We applied the methods to an illustrative example in chronic myeloid leukemia to investigate the surrogate relationship between complete cytogenetic response (CCyR) and event-free-survival (EFS).
In this article, we analyze perinatal data with birth weight (BW) as primarily interesting response variable. Gestational age (GA) is usually an important covariate and included in polynomial form. However, in opposition to this univariate regression, bivariate modeling of BW and GA is recommended to distinguish effects on each, on both, and between them. Rather than a parametric bivariate distribution, we apply conditional copula regression, where marginal distributions of BW and GA (not necessarily of the same form) can be estimated independently, and where the dependence structure is modele…
A bivariate distribution with continuous margins can be uniquely decomposed via a copula and its marginal distributions. We consider the problem of estimating the copula function and adopt a Bayesian approach. On the space of copula functions, we construct a finite-dimensional approximation subspace that is parametrized by a doubly stochastic matrix. A major problem here is the selection of a prior distribution on the space of doubly stochastic matrices also known as the Birkhoff polytope. The main contributions of this paper are the derivation of a simple formula for the Jeffreys prior and sh…
Copulas allow to learn marginal distributions separately from the multivariate dependence structure (copula) that links them together into a density function. Vine factorizations ease the learning of high-dimensional copulas by constructing a hierarchy of conditional bivariate copulas. However, to simplify inference, it is common to assume that each of these conditional bivariate copulas is independent from its conditioning variables. In this paper, we relax this assumption by discovering the latent functions that specify the shape of a conditional copula given its conditioning variables We le…
Conditional copulas are flexible statistical tools that couple joint conditional and marginal conditional distributions. In a linear regression setting with more than one covariate and two dependent outcomes, we propose the use of additive models for conditional bivariate copula models and discuss computation and model selection tools for performing Bayesian inference. The method is illustrated using simulations and a real example.
There exist many bivariate parametric copulas to model bivariate data with different dependence features. We propose a new bivariate parametric copula family that cannot only handle various dependence patterns that appear in the existing parametric bivariate copula families, but also provides a more enriched dependence structure. The proposed copula construction exploits finite mixtures of bivariate normal distributions. The mixing operation, the distinct correlation and mean parameters at each mixture component introduce quite a flexible dependence. The new parametric copula is theoretically …
Parametric conditional copula models allow the copula parameters to vary with a set of covariates according to an unknown calibration function. Flexible Bayesian inference for the calibration function of a bivariate conditional copula is proposed via a sparse Gaussian process (GP) prior distribution over the set of smooth calibration functions for the single index model (SIM). The estimation of parameters from the marginal distributions and the calibration function is done jointly via Markov Chain Monte Carlo sampling from the full posterior distribution. A new Conditional Cross Validated Pseu…
We study the behavior of bivariate empirical copula process $\mathbb{G}_n(\cdot,\cdot)$ on pavements $[0,k_n/n]^2$ of $[0,1]^2,$ where $k_n$ is a sequence of positive constants fulfilling some conditions. We provide a upper bound for the strong approximation of $\mathbb{G}_n(\cdot,\cdot)$ by a Gaussian process when $k_n/n \searrow γ$ as $n\rightarrow \infty,$ where $0 \leq γ\leq 1.$
Université du Québec à Montréal（蒙特利尔魁北克大学）；Université de Montréal（蒙特利尔大学）；Université catholique de Louvain（天主教鲁汶大学）
A recommender system based on ranks is proposed, where an expert's ranking of a set of objects and a user's ranking of a subset of those objects are combined to make a prediction of the user's ranking of all objects. The rankings are assumed to be induced by latent continuous variables corresponding to the grades assigned by the expert and the user to the objects. The dependence between the expert and user grades is modelled by a copula in some parametric family. Given a prior distribution on the copula parameter, the user's complete ranking is predicted by the mode of the posterior predictive…
We propose a copula-based measure of asymmetry between the lower and upper tail probabilities of bivariate distributions. The proposed measure has a simple form and possesses some desirable properties as a measure of asymmetry. The limit of the proposed measure as the index goes to the boundary of its domain can be expressed in a simple form under certain conditions on copulas. A sample analogue of the proposed measure for a sample from a copula is presented and its weak convergence to a Gaussian process is shown. Another sample analogue of the presented measure, which is based on a sample fro…
In this work we propose a semiparametric bivariate copula whose density is defined by a piecewise constant function on disjoint squares. We obtain the maximum likelihood estimators of model parameters and prove that they reduce to the sample copula under specific conditions. We further propose to carry out a full Bayesian analysis of the model and introduce a spatial dependent prior distribution for the model parameters. This prior allows the parameters to borrow strength across neighbouring regions to produce smooth posterior estimates. To characterise the posterior distribution, via the full…
Vine copulas allow to build flexible dependence models for an arbitrary number of variables using only bivariate building blocks. The number of parameters in a vine copula model increases quadratically with the dimension, which poses new challenges in high-dimensional applications. To alleviate the computational burden and risk of overfitting, we propose a modified Bayesian information criterion (BIC) tailored to sparse vine copula models. We show that the criterion can consistently distinguish between the true and alternative models under less stringent conditions than the classical BIC. The …
Approximate Bayesian computation (ABC) refers to a family of inference methods used in the Bayesian analysis of complex models where evaluation of the likelihood is difficult. Conventional ABC methods often suffer from the curse of dimensionality, and a marginal adjustment strategy was recently introduced in the literature to improve the performance of ABC algorithms in high-dimensional problems. The marginal adjustment approach is extended using a Gaussian copula approximation. The method first estimates the bivariate posterior for each pair of parameters separately using a 2-dimensional Gaus…
Diagnostic test accuracy studies typically report the number of true positives, false positives, true negatives and false negatives. There usually exists a negative association between the number of true positives and true negatives, because studies that adopt less stringent criterion for declaring a test positive invoke higher sensitivities and lower specificities. A generalized linear mixed model (GLMM) is currently recommended to synthesize diagnostic test accuracy studies. We propose a copula mixed model for bivariate meta-analysis of diagnostic test accuracy studies. Our general model inc…
We first review an approach that had been developed in the past years to introduce concepts of "bivariate ageing" for exchangeable lifetimes and to analyze mutual relations among stochastic dependence, univariate ageing, and bivariate ageing. A specific feature of such an approach dwells on the concept of semi-copula and in the extension, from copulas to semi-copulas, of properties of stochastic dependence. In this perspective, we aim to discuss some intricate aspects of conceptual character and to provide the readers with pertinent remarks from a Bayesian Statistics standpoint. In particular …
In this paper, we consider bivariate composite models for modeling jointly different types of claims and their associated costs in a flexible manner. For expository purposes, the Gumbel copula is paired with the composite Weibull-Inverse Weibull, Paralogistic-Inverse Weibull, and Inverse Burr-Inverse Weibull marginal models. The resulting bivariate copula-based composite models are fitted on motor insurance bodily injury and property damage data from a European motor insurance company and their parameters are estimated via the inference functions for margins method.
Vine copulas are a highly flexible class of dependence models, which are based on the decomposition of the density into bivariate building blocks. For applications one usually makes the simplifying assumption that copulas of conditional distributions are independent of the variables on which they are conditioned. However this assumption has been criticised for being too restrictive. We examine both simplified and non-simplified vine copulas in three dimensions and investigate conceptual differences. We show and compare contour surfaces of three-dimensional vine copula models, which prove to be…
In genome wide association studies (GWAS), researchers are often dealing with non-normally distributed traits or a mixture of discrete-continuous traits. However, most of the current region-based methods rely on multivariate linear mixed models (mvLMMs) and assume a multivariate normal distribution for the phenotypes of interest. Hence, these methods are not applicable to disease or non-normally distributed traits. Therefore, there is a need to develop unified and flexible methods to study association between a set of (possibly rare) genetic variants and non-normal multivariate phenotypes. Cop…
Several collective risk models have recently been proposed by relaxing the widely used but controversial assumption of independence between claim frequency and severity. Approaches include the bivariate copula model, random effect model, and two-part frequency-severity model. This study focuses on the copula approach to develop collective risk models that allow a flexible dependence structure for frequency and severity. We first revisit the bivariate copula method for frequency and average severity. After examining the inherent difficulties of the bivariate copula model, we alternatively propo…
In medical studies, it is common the presence of a fraction of patients who do not experience the event of interest. These patients are people who are not at risk of the event or are patients who were cured during the research. The proportion of immune or cured patients is known in the literature as cure rate. In general, the traditional existing lifetime statistical models are not appropriate to model data sets with cure rate, including bivariate lifetimes. In this paper, it is proposed a bivariate model based on a defective Gompertz distribution and also using a Clayton copula function to ca…
A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that is superior to the standard generalized linear mixed model (GLMM) in this context. Here we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate GLMM as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analysing the data o…
Several gene-based association tests for time-to-event traits have been proposed recently, to detect whether a gene region (containing multiple variants), as a set, is associated with the survival outcome. However, for bivariate survival outcomes, to the best of our knowledge, there is no statistical method that can be directly applied for gene-based association analysis. Motivated by a genetic study to discover gene regions associated with the progression of a bilateral eye disease, Age-related Macular Degeneration (AMD), we implement a novel functional regression method under the copula fram…
In probability and statistics, reliable modeling of bivariate continuous characteristics remains a real insurmountable consideration. During analysis of bivariate data, we have to deal with heterogeneity that is present in data. Therefore, for dealing with such a scenario, we investigate a novel technique based on a Farlie-Gumbel-Morgenstern (FGM) copula and the inverse Topp-Leone (ITL) model in this study. The idea is to use the oscillating functionalities of the FGM copula and the flexibility of the ITL model to propose a serious bivariate solution for the modeling of bivariate lifetime phen…
Bivariate Frank Copula: Some More Results on Point Estimation of the Association Parameter from a Bayesian Perspective and Revisiting the Goodness of Fit Tests with an Application to Model Groundwater Data from Dong Thap, Vietnam
Faculty of Applied Science, Ho Chi Minh City University of Technology (HCMUT)（胡志明市理工大学应用科学学院）；Vietnam National University Ho Chi Minh City（越南国家大学胡志明市分校）；Faculty of Mathematics and Statistics, Ton Duc Thang University（Ton Duc Thang大学数学与统计学院）
Poverty is a multidimensional concept often comprising a monetary outcome and other welfare dimensions such as education, subjective well-being or health, that are measured on an ordinal scale. In applied research, multidimensional poverty is ubiquitously assessed by studying each poverty dimension independently in univariate regression models or by combining several poverty dimensions into a scalar index. This inhibits a thorough analysis of the potentially varying interdependence between the poverty dimensions. We propose a multivariate copula generalized additive model for location, scale a…
This paper intends to develop tools for characterizing non-linear spectral dependence between spontaneous brain signals. We use parametric copula models (both bivariate and vine models) applied on the magnitude of Fourier coefficients rather than using coherence. The motivation behind this work is an experiment on rats that studied the impact of stroke on the connectivity structure (dependence) between local field potentials recorded at various channels. We address the following major questions. First, we ask whether one can detect any changepoint in the regime of a brain channel for a given f…
Our goal in this paper is to propose an alternative risk measure which takes into account the fluctuations of losses and possible correlations between random variables. This new notion of risk measures, that we call Copula Conditional Tail Expectation describes the expected amount of risk that can be experienced given that a potential bivariate risk exceeds a bivariate threshold value, and provides an important measure for right-tail risk. An application to real financial data is given.
Asymmetry is an inherent property of bivariate associations and therefore must not be ignored. The currently applicable dependence measures mask the potential asymmetry of the underlying dependence structure by implicitly assuming that quantity Y is equally dependent on quantity X, and vice versa, which is generally not true. We introduce the copula-based dependence measure qad that quantifies asymmetry. Specifically, qad is applicable in general situations, is sensitive to noise in data, detects asymmetry in dependence and reliably quantifies the information gain/predictability of quantity Y …
Copula models have been widely used to model the dependence between continuous random variables, but modeling count data via copulas has recently become popular in the statistics literature. Spearman's rho is an appropriate and effective tool to measure the degree of dependence between two random variables. In this paper, we derived the population version of Spearman's rho correlation via copulas when both random variables are discrete. The closed-form expressions of the Spearman correlation are obtained for some copulas of simple structure such as Archimedean copulas with different marginal d…
