title: Severe COPD Exacerbation Risk and Long-Acting Bronchodilator Treatments: Comparison of Three Observational Data Analysis Methods.
abstract: OBJECTIVE
  Results from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations.
  
  
  METHODS
  Severe exacerbation risk was assessed over a 2-year period using claims data for patients aged ≥40 years who initiated long-acting muscarinic antagonist (LAMA), inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), or triple therapy (LAMA + ICS/LABA).
  
  
  RESULTS
  A total of 5475 COPD patients met inclusion criteria. Six months post-initiation, 53.5 % of patients discontinued using any therapy. The ITT analysis found an increased severe exacerbation risk for triple therapy treatment (hazard ratio [HR] 1.24; 95 % confidence interval [CI] 1.00-1.53). No increased risk was found in the AP (HR 1.00; 95 % CI 0.73-1.36), or MSM analyses (HR 1.11; 95 % CI 0.68-1.81). The MSM highlighted important associations among post-index events.
  
  
  CONCLUSIONS
  Neglecting to adjust for treatment discontinuation may produce biased risk estimates. The MSM approach is a promising tool to compare chronic disease management by illuminating relationships between treatment decisions, adherence, patient choices, and outcomes.
authors.affiliation: Health Services Research Division, LCF Research, 2309 Renard Place SE, Suite 103, Albuquerque, NM, 87106, USA. mroberts@lcfresearch.org.|College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. mroberts@lcfresearch.org.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Roberts
authors.affiliation: Health Services Research Division, LCF Research, 2309 Renard Place SE, Suite 103, Albuquerque, NM, 87106, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Mapel
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Borrego
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.affiliation: College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Georgopoulos
authors.affiliation: Department of Economics, University of New Mexico, Albuquerque, NM, USA.
authors.forename: David
authors.initials: D
authors.lastname: van der Goes