Copd_a_230955 1529..1543

s reporting supplementary results of previously published studies. Other sources included ClinicalTrials. gov, the International Clinical Trials Registry Platform, the Australian New Zealand Clinical Trials Registry, the GlaxoSmithKline Study Register, and company websites. A first-stage screening process was conducted to review citations based on the article title and the abstract. Citations not matching the eligibility criteria were excluded at this stage, based on a pre-defined exclusion reason. Also, any duplicate citations were excluded. Two independent reviewers screened all citations, and a third independent reviewer resolved any discrepancies. Following the completion of the first-stage screening, the full texts of relevant studies were retrieved and examined in more detail to determine a final list of included studies. Two independent reviewers screened the full-text articles, with any discrepancies resolved by a third independent reviewer. For all relevant studies, details of the study characteristics, eligibility criteria, patient characteristics, and overall conclusions were extracted. To determine the risk of bias for each included RCT, the methodological quality of the study was assessed against a list of criteria relating to randomization and allocation concealment, baseline comparability, blinding, follow-up, selective reporting, and data analysis, including handling of missing data. Indirect Evidence A second literature search was performed to identify any indirect evidence. Eligible publications were systematic or targeted literature reviews with any quantitative analysis component, or meta-analyses, indirect treatment comparisons, or NMAs assessing comparative efficacy, safety and/or tolerability of LAMA/LABAs FDCs in patients with COPD with moderate-to-very severe airflow limitation. Only studies with full text inEnglishwere included.Analyses thatwere not based on RCTs were excluded from the review. The full search strategy (including search terms) is presented in the Supplementary Materials (Supplementary Table 1). Biomedical databases including MEDLINE, MEDLINE InProcess, EMBASE, and CENTRAL were reviewed, and bibliographic screening of relevant published reviews was conducted. The databases were searched from their date of inception to January 2020. Also, various Health Technology Assessment databases were searched, including the National Institute for Health and Care Excellence, the Scottish Medicines Consortium, the Canadian Agency for Drugs and Technologies in Health, the Pharmaceutical Benefits Advisory Committee, the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, andHaute Autorité de Santé. Following an initial screen of retrieved citations by a single independent reviewer, a quality assessment of a 20% random sample was performed by a second independent reviewer. A first-stage screening process was conducted as described above for the direct evidence. Full texts of relevant studies were then retrieved to determine whether eligibility criteria of the literature review were met. For the current review, details of the characteristics of the analysis, eligibility criteria, patient characteristics, and overall conclusions were extracted. Also, details of any inconsistency testing conducted to assess whether there was any conflict between direct and indirect evidence were reviewed. The methodological quality (relevance and credibility) of all included indirect analyses was assessed using the International Society for Pharmacoeconomics and Outcomes Research consensusbased 26-item questionnaire. The final review focused on NMAs that reported efficacy outcomes at 12 and 24 weeks of treatment, established durations of symptomatic studies in COPD recommended by regulators. Results Direct Evidence: Study Characteristics Using the results of the systematic literature review, four RCTs from three publications were identified that provided head-to-head comparison of LAMA/LABA FDCs in patients with moderate-to-very severe airflow limitation in COPD (Figure 1): the AERISTO study, a 24-week, multicenter, international, Phase IIIb, double-blind study; Study A2349 and Study A2350, two identically designed 12-week, multicenter, US, Phase III, doubleblind studies; and Study GSK204990, an 8-week, multicenter, international, Phase IV, open-label study. In terms of the characteristics of the studies identified in the literature search, some differences were noted across the studies in treatment duration, study design (parallelgroup vs the crossover), the number of patients randomized, and levels of blinding (Table 1). All four RCTs included umeclidinium/vilanterol DPI as one of the study treatments; this was compared with glycopyrrolate/formoterol fumarate pressurized metered dose inhaler in one study (AERISTO), indacaterol/glycopyrrolate DPI in two studies (Study A2349 and Study A2350), and tiotropium/ olodaterol SMI in one study (Study GSK204990). Dovepress Hurst et al International Journal of Chronic Obstructive Pulmonary Disease 2020:15 submit your manuscript | www.dovepress.com DovePress 1531 In te rn at io na l J ou rn al o f C hr on ic O bs tr uc tiv e P ul m on ar y D is ea se d ow nl oa de d fr om h ttp s: //w w w .d ov ep re ss .c om / b y 19 3. 60 .2 38 .9 9 on 0 4A ug -2 02 0 F or p er so na l u se o nl y. Powered by TCPDF (www.tcpdf.org)