title: Systematic Review and Quality Appraisal of Cost-Effectiveness Analyses of Pharmacologic Maintenance Treatment for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Recommendations.
abstract: Worldwide, chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease with considerable clinical and socioeconomic impact. Pharmacologic maintenance drugs (such as bronchodilators and inhaled corticosteroids) play an important role in the treatment of COPD. The cost effectiveness of these treatments has been frequently assessed, but studies to date have largely neglected the impact of treatment sequence and the exact stage of disease in which the drugs are used in real life.
  
  
  
  We aimed to systematically review recently published articles that reported the cost effectiveness of COPD maintenance treatments, with a focus on key findings, quality and methodological issues.
  
  
  
  We performed a systematic literature search in Embase, PubMed, the UK NHS Economic Evaluation Database (NHS-EED) and EURONHEED (European Network of Health Economics Evaluation Databases) and included all relevant articles published between 2011 and 2015 in either Dutch, English or German. Main study characteristics, methods and outcomes were extracted and critically assessed. The Quality of Health Economic Studies (QHES) instrument was used as basis for quality assessment, but additional items were also addressed.
  
  
  
  The search identified 18 recent pharmacoeconomic analyses of COPD maintenance treatments. Papers reported the cost effectiveness of long-acting muscarinic antagonist (LAMA) monotherapy (n = 6), phosphodiesterase (PDE)-4 inhibitors (n = 4), long-acting beta agonist/inhaled corticosteroid (LABA/ICS) combinations (n = 4), LABA monotherapy (n = 2) and LABA/LAMA combinations (n = 2). All but two studies were funded by the manufacturer, and all studies indicated favourable cost effectiveness; however, the number of quality-adjusted life-years (QALYs) gained was small. Less than half of the studies reported a COPD-specific outcome in addition to a generic outcome (mostly QALYs). Exacerbation and mortality rates were found to be the main drivers of cost effectiveness. According to the QHES, the quality of the studies was generally sufficient, but additional assessment revealed that most studies poorly represented the cost effectiveness of real-life medication use.
  
  
  
  The majority of studies showed that pharmacologic COPD maintenance treatment is cost effective, but most studies poorly reflected real-life drug use. Consistent and COPD-specific methodology is recommended.
authors: Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors: Simon
authors: S
authors: van der Schans
authors: Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors: Lucas M A
authors: LMA
authors: Goossens
authors: Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors: Melinde R S
authors: MRS
authors: Boland
authors: Department of General Practice, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
authors: Janwillem W H
authors: JWH
authors: Kocks
authors: Unit of Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.|Institute of Science in Healthy Aging & healthcaRE (SHARE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Maarten J
authors: MJ
authors: Postma
authors: Department of General Practice, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. j.f.m.van.boven@rug.nl.|Center for Pharmaceutical Outcomes Research, School of Pharmacy, University of Colorado, Denver, CO, USA. j.f.m.van.boven@rug.nl.
authors: Job F M
authors: JFM
authors: van Boven
authors: Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands.
authors: Maureen P M H
authors: MPMH
authors: Rutten-van Mölken
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000191:economics; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000191:economics; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D017850:Economics, Pharmaceutical; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000191:economics; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000191:economics; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000191:economics; D019057:Quality-Adjusted Life Years
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D058988:Phosphodiesterase 4 Inhibitors