{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:42:27Z","timestamp":1788194547245,"version":"build-2803163510"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T00:00:00Z","timestamp":1524009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM70335"],"award-info":[{"award-number":["GM70335"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01CA142538"],"award-info":[{"award-number":["P01CA142538"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Program of National Institutes of Health"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Low-density lipoprotein cholesterol (LDL-C) has been identified as a causative factor for atherosclerosis and related coronary heart disease, and as the main target for cholesterol- and lipid-lowering therapy. Statin drugs inhibit cholesterol synthesis in the liver and are typically the first line of therapy to lower elevated levels of LDL-C. On the other hand, a different drug, Ezetimibe, inhibits the absorption of cholesterol by the small intestine and provides a different mechanism of action. Many clinical trials have been carried out on safety and efficacy evaluation of cholesterol lowering drugs. To synthesize the results from different clinical trials, we examine treatment level (aggregate) network meta-data from 29 double-blind, randomized, active, or placebo-controlled statins +\/$-$ Ezetimibe clinical trials on adult treatment-na\u00efve patients with primary hypercholesterolemia. In this article, we propose a new approach to carry out Bayesian inference for arm-based network meta-regression. Specifically, we develop a new strategy of grouping the variances of random effects, in which we first formulate possible sets of the groups of the treatments based on their clinical mechanisms of action and then use Bayesian model comparison criteria to select the best set of groups. The proposed approach is especially useful when some treatment arms are involved in only a single trial. In addition, a Markov chain Monte Carlo sampling algorithm is developed to carry out the posterior computations. In particular, the correlation matrix is generated from its full conditional distribution via partial correlations. The proposed methodology is further applied to analyze the network meta-data from 29 trials with 11 treatment arms.<\/jats:p>","DOI":"10.1093\/biostatistics\/kxy014","type":"journal-article","created":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T20:10:14Z","timestamp":1521749414000},"page":"499-516","source":"Crossref","is-referenced-by-count":4,"title":["Bayesian inference for network meta-regression using multivariate random effects with applications to cholesterol lowering drugs"],"prefix":"10.1093","volume":"20","author":[{"given":"Hao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Statistics, University of Connecticut, Storrs, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Connecticut, Storrs, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungduk","family":"Kim","sequence":"additional","affiliation":[{"name":"Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind K","family":"Shah","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Lin","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M","family":"Tershakovec","sequence":"additional","affiliation":[{"name":"Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,18]]},"reference":[{"key":"2019080206202622500_B1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/clc.22577","article-title":"Prevalence and factors associated with statin use among a nationally representative sample of US adults: National Health and Nutrition Examination Survey, 2011\u20132012.","volume":"9","author":"Adedinsewo","year":"2016","journal-title":"Clinical Cardiology"},{"key":"2019080206202622500_B2","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1161\/01.CIR.0000068312.21969.C8","article-title":"Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia.","volume":"19","author":"Ballantyne","year":"2003","journal-title":"Circulation"},{"key":"2019080206202622500_B3","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0140-6736(05)71879-1","article-title":"Epidemiology and reporting of randomised trials published in PubMed journals.","volume":"9465","author":"Chan","year":"2005","journal-title":"The Lancet"},{"key":"2019080206202622500_B4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/10618600.1999.10474802","article-title":"Monte Carlo estimation of Bayesian credible and HPD intervals.","volume":"1","author":"Chen","year":"1999","journal-title":"Journal of Computational and Graphical Statistics"},{"key":"2019080206202622500_B5","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4612-1276-8","volume-title":"Monte Carlo Methods in Bayesian Computation","author":"Chen","year":"2000"},{"key":"2019080206202622500_B6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF00162502","article-title":"A Bayesian predictive approach to determining the number of components in a mixture distribution.","volume":"4","author":"Dey","year":"1995","journal-title":"Statistics and Computing"},{"key":"2019080206202622500_B7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/jrsm.1184","article-title":"Absolute or relative effects? Arm-based synthesis of trial data.","volume":"7","author":"Dias","year":"2016","journal-title":"Research Synthesis Methods"},{"key":"2019080206202622500_B8","first-page":"2486","article-title":"Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III).","volume-title":"Journal of American Medical Association","author":"Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults","year":"2001"},{"key":"2019080206202622500_B9","article-title":"Network meta-regression for ordinal outcomes: applications in comparing Crohn\u2019s disease treatments.","volume-title":"Technical Report 16\u201328","author":"Gwon","year":"2016"},{"key":"2019080206202622500_B10","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1177\/0272989X13481110","article-title":"Comparing Bayesian and frequentist approaches for multiple outcome mixed treatment comparisons.","volume":"5","author":"Hong","year":"2013","journal-title":"Medical Decision Making"},{"key":"2019080206202622500_B11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/jrsm.1153","article-title":"A Bayesian missing data framework for generalized multiple outcome mixed treatment comparisons.","volume":"7","author":"Hong","year":"2016","journal-title":"Research Synthesis Methods"},{"key":"2019080206202622500_B12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1201\/9781315159409-13","article-title":"Bayesian network meta-analysis for multiple endpoints.","volume-title":"Methods in Comparative Effectiveness Research","author":"Hong","year":"2017"},{"key":"2019080206202622500_B13","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1002\/(SICI)1097-0258(19961230)15:24<2733::AID-SIM562>3.0.CO;2-0","article-title":"Borrowing strength from external trials in a meta-analysis.","volume":"24","author":"Higgins","year":"1996","journal-title":"Statistics in Medicine"},{"key":"2019080206202622500_B14","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3447-8","volume-title":"Bayesian Survival Analysis","author":"Ibrahim","year":"2001"},{"key":"2019080206202622500_B15","doi-asserted-by":"crossref","first-page":"543","DOI":"10.4065\/82.5.543","article-title":"Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial.","volume":"5","author":"Insull","year":"2007","journal-title":"Mayo Clinic Proceedings"},{"key":"2019080206202622500_B16","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.jmva.2005.05.010","article-title":"Generating random correlation matrices based on partial correlations.","volume":"10","author":"Joe","year":"2006","journal-title":"Journal of Multivariate Analysis"},{"key":"2019080206202622500_B17","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1002\/sim.1875","article-title":"Combination of direct and indirect evidence in mixed treatment comparisons.","volume":"20","author":"Lu","year":"2004","journal-title":"Statistics in Medicine"},{"key":"2019080206202622500_B18","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1198\/016214505000001302","article-title":"Assessing evidence inconsistency in mixed treatment comparisons.","volume":"474","author":"Lu","year":"2006","journal-title":"Journal of the American Statistical Association"},{"key":"2019080206202622500_B19","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1093\/biostatistics\/kxp032","article-title":"Modeling between-trial variance structure in mixed treatment comparisons.","volume":"10","author":"Lu","year":"2009","journal-title":"Biostatistics"},{"key":"2019080206202622500_B20","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1002\/sim.1201","article-title":"Network meta-analysis for indirect treatment comparisons.","volume":"16","author":"Lumley","year":"2002","journal-title":"Statistics in Medicine"},{"key":"2019080206202622500_B21","doi-asserted-by":"crossref","first-page":"f5195","DOI":"10.1136\/bmj.f5195","article-title":"The effects of excluding treatments from network meta-analyses: survey.","volume":"347","author":"Mills","year":"2013","journal-title":"British Medical Journal"},{"key":"2019080206202622500_B22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.atherosclerosis.2012.02.016","article-title":"Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: A pooled analysis of over 21,000 subjects from 27 clinical trials.","volume":"223","author":"Morrone","year":"2012","journal-title":"Atherosclerosis"},{"key":"2019080206202622500_B23","volume-title":"A Blog of the National Center for Health Center for Health Statistics","author":"NCHStats","year":"2013"},{"key":"2019080206202622500_B24","author":"Ross","year":"2015","journal-title":"Too Few Americans Take Statins, CDC Study Reveals"},{"key":"2019080206202622500_B25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.jclinepi.2010.03.016","article-title":"Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial.","volume":"2","author":"Salanti","year":"2011","journal-title":"Journal of Clinical Epidemiology"},{"key":"2019080206202622500_B26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/1467-9868.00353","article-title":"Bayesian measures of model complexity and fit.","volume":"4","author":"Spiegelhalter","year":"2002","journal-title":"Journal of the Royal Statistical Society: Series B (Statistical Methodology)"},{"key":"2019080206202622500_B27","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1080\/10543406.2011.590923","article-title":"Bayesian modeling and inference for meta data with applications in efficacy evaluation of an allergic rhinitis drug.","volume":"5","author":"Yao","year":"2011","journal-title":"Journal of Biopharmaceutical Statistics"},{"key":"2019080206202622500_B28","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1080\/01621459.2015.1006065","article-title":"Bayesian inference for multivariate meta-regression with partially observed within-study sample covariance matrix.","volume":"510","author":"Yao","year":"2015","journal-title":"Journal of the American Statistical Association"}],"container-title":["Biostatistics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biostatistics\/article-pdf\/20\/3\/499\/29093147\/kxy014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T06:52:20Z","timestamp":1719903140000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biostatistics\/article\/20\/3\/499\/4975593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,18]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,4,18]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/biostatistics\/kxy014","relation":{},"ISSN":["1465-4644","1468-4357"],"issn-type":[{"value":"1465-4644","type":"print"},{"value":"1468-4357","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2018,4,18]]}}}