{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:13:55Z","timestamp":1747196035106,"version":"3.40.5"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Institute of Artificial Intelligence and Robotics for Society","award":["No. 2021-ICP001"],"award-info":[{"award-number":["No. 2021-ICP001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>2021 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Reports recommends that patients with clinically significant symptoms and exacerbations of chronic obstructive pulmonary disease (COPD) should escalate to triple therapy, a combined use of inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting b2-agonists (LABA)(ICS\/LAMA\/LABA). Triple therapy in fixed-dose combinations (FDCs), i.e., combining ICS, LABA with LAMA and administrating by a single inhalation device, has appeared in recent years. This study aims to compare the efficacy of triple therapy in FDCs in treating patients with moderate to severe COPD.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and analyses<\/jats:title>\n<jats:p>Literature search will be conducted on PubMed, Embase and Web of science, according to pre-specified and corresponding search strategies, for relevant reports published since the inception dates of the databases. Randomised controlled trials (RCT) which compared the triple therapy in FDCs with other pharmacological therapies will be included. The Cochrane risk of bias assessment tool (RoB 2) will be used to assess the RCT quality. The outcomes will be analyzed as rate ratios and mean differences under a random-effects model in a frequentist network meta-analysis (NMA). Additional statistical analyses including subgroup analysis, sensitivity analysis, and publication bias analysis will be performed to assess the evidential heterogeneity and robustness. The strength of evidence from the NMA will be evaluated with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) methods.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Ethics and dissemination<\/jats:title>\n<jats:p>No ethics approval is required as this systematic review and network meta-analysis do not collect confidential personal data and do not carry out interventions in treating patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Protocol registration number<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/CRD42021240823\" xlink:type=\"simple\">CRD42021240823<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0255545","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T18:08:16Z","timestamp":1628186896000},"page":"e0255545","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative efficacy of single-inhaler triple therapies for COPD: A protocol for systematic review and network 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