title: A mixed effect model for bivariate meta-analysis of diagnostic test accuracy studies using a copula representation of the random effects distribution.
abstract: 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 includes the GLMM as a special case and can also operate on the original scale of sensitivity and specificity. Summary receiver operating characteristic curves are deduced for the proposed model through quantile regression techniques and different characterizations of the bivariate random effects distribution. Our general methodology is demonstrated with an extensive simulation study and illustrated by re-analysing the data of two published meta-analyses. Our study suggests that there can be an improvement on GLMM in fit to data and makes the argument for moving to copula random effects models. Our modelling framework is implemented in the package CopulaREMADA within the open source statistical environment R.
authors.affiliation: School of Computing Sciences, University of East Anglia, Norwich NR4 7TJ, U.K.
authors.forename: Aristidis K
authors.identifier: http://orcid.org/0000-0003-0853-0084
authors.initials: AK
authors.lastname: Nikoloulopoulos
mesh_terms: D016208:Databases, Factual / Q000706:statistics & numerical data; D019937:Diagnostic Techniques and Procedures / Q000592:standards / Q000706:statistics & numerical data*; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D008220:Lymphography / Q000706:statistics & numerical data; D015201:Meta-Analysis as Topic; D012372:ROC Curve; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D019098:Telomerase; D014057:Tomography, X-Ray Computed / Q000706:statistics & numerical data
chemical_list: D019098:Telomerase
keywords: SROC, sensitivity/specificity; copula models; diagnostic tests; multivariate meta-analysis; random effects models