title: Meta-analysis methods and models with applications in evaluation of cholesterol-lowering drugs.
abstract: In this paper, we propose a class of multivariate random effects models allowing for the inclusion of study-level covariates to carry out meta-analyses. As existing algorithms for computing maximum likelihood estimates often converge poorly or may not converge at all when the random effects are multi-dimensional, we develop an efficient expectation-maximization algorithm for fitting multi-dimensional random effects regression models. In addition, we also develop a new methodology for carrying out variable selection with study-level covariates. We examine the performance of the proposed methodology via a simulation study. We apply the proposed methodology to analyze metadata from 26 studies involving statins as a monotherapy and in combination with ezetimibe. In particular, we compare the low-density lipoprotein cholesterol-lowering efficacy of monotherapy and combination therapy on two patient populations (naïve and non-naïve patients to statin monotherapy at baseline), controlling for aggregate covariates. The proposed methodology is quite general and can be applied in any meta-analysis setting for a wide range of scientific applications and therefore offers new analytic methods of clinical importance.
authors: Department of Statistics, University of Connecticut, Storrs, CT, USA.
authors: Ming-Hui
authors: MH
authors: Chen
authors: Joseph G
authors: JG
authors: Ibrahim
authors: Arvind K
authors: AK
authors: Shah
authors: Jianxin
authors: J
authors: Lin
authors: Hui
authors: H
authors: Yao
mesh_terms: D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000008:administration & dosage / Q000009:adverse effects / Q000187:drug effects; D003198:Computer Simulation; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005069:Evaluation Studies as Topic; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D016013:Likelihood Functions; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000502:physiology; D015201:Meta-Analysis as Topic; D015999:Multivariate Analysis; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D000069438:Ezetimibe