title: Statistical Modeling of Disease Progression for Chronic Obstructive Pulmonary Disease Using Data from the ECLIPSE Study.
abstract: To develop statistical models predicting disease progression and outcomes in chronic obstructive pulmonary disease (COPD), using data from ECLIPSE, a large, observational study of current and former smokers with COPD.
  
  
  
  Based on a conceptual model of COPD disease progression and data from 2164 patients, associations were made between baseline characteristics, COPD disease progression attributes (exacerbations, lung function, exercise capacity, and symptoms), health-related quality of life (HRQoL), and survival. Linear and nonlinear functional forms of random intercept models were used to characterize these relationships. Endogeneity was addressed by time-lagging variables in the regression models.
  
  
  
  At the 5% significance level, an exacerbation history in the year before baseline was associated with increased risk of future exacerbations (moderate: +125.8%; severe: +89.2%) and decline in lung function (forced expiratory volume in 1 second [FEV1]) (-94.20 mL per year). Each 1% increase in FEV1% predicted was associated with decreased risk of exacerbations (moderate: -1.1%; severe: -3.0%) and increased 6-minute walk test distance (6MWD) (+1.5 m). Increases in baseline exercise capacity (6MWD, per meter) were associated with slightly increased risk of moderate exacerbations (+0.04%) and increased FEV1(+0.62 mL). Symptoms (dyspnea, cough, and/or sputum) were associated with an increased risk of moderate exacerbations (+13.4% to +31.1%), and baseline dyspnea (modified Medical Research Council score ≥2 v. <2) was associated with lower FEV1(-112.3 mL).
  
  
  
  A series of linked statistical regression equations have been developed to express associations between indicators of COPD disease severity and HRQoL and survival. These can be used to represent disease progression, for example, in new economic models of COPD.
authors.affiliation: ICON, San Francisco, CA, USA (AE, CC).
authors.forename: Alex
authors.initials: A
authors.lastname: Exuzides
authors.affiliation: ICON, San Francisco, CA, USA (AE, CC).
authors.forename: Chris
authors.initials: C
authors.lastname: Colby
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK (AHB).|ICON Health Economics, Morristown, NJ, USA (AHB).
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Briggs
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London, UK (DAL).
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.affiliation: Institute for Medical Technology Assessment, Erasmus University, Rotterdam, Netherlands (MPMHRvM).
authors.forename: Maureen P M H
authors.initials: MPMH
authors.lastname: Rutten-van Mölken
authors.affiliation: Value Evidence and Outcomes, GSK R&D, Uxbridge, UK (MT, SG-M).
authors.forename: Maggie
authors.initials: M
authors.lastname: Tabberer
authors.affiliation: Global Market Access and Healthcare Solutions, GSK, Brentford, UK (MC).
authors.forename: Mike
authors.initials: M
authors.lastname: Chambers
authors.affiliation: Worldwide Epidemiology, GSK R&D, Uxbridge, UK (HM).
authors.forename: Hana
authors.initials: H
authors.lastname: Muellerova
authors.affiliation: GSK R&D, Research Triangle Park, NC, USA (NL).
authors.forename: Nicholas
authors.initials: N
authors.lastname: Locantore
authors.affiliation: Oxford Outcomes, Toronto, ON, Canada (NR).
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Risebrough
authors.affiliation: Value Evidence and Outcomes, GSK R&D, Research Triangle Park, NC, USA (ASI).|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada (ASI).
authors.forename: Afisi S
authors.initials: AS
authors.lastname: Ismaila
authors.affiliation: Value Evidence and Outcomes, GSK R&D, Uxbridge, UK (MT, SG-M).
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gonzalez-McQuire
mesh_terms: D000368:Aged; D015415:Biomarkers; D015992:Body Mass Index; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D006296:Health Services / Q000706:statistics & numerical data; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000191:economics / Q000401:mortality* / Q000503:physiopathology*; D011788:Quality of Life; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D012959:Socioeconomic Factors; D016019:Survival Analysis
chemical_list: D015415:Biomarkers
keywords: St George’s Respiratory Questionnaire; exacerbation; lung function; mixed models; survival