Systematic Review and Quality Appraisal of Cost-Effectiveness Analyses of Pharmacologic Maintenance Treatment for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Recommendations

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Fig. 1

Flow diagram of the search performed. COPD chronic obstructive pulmonary disease

Fig. 2

Percentage of maximum Quality of Health Economic Studies (QHES) score per question across the total of studies. Q1: Was the study objective presented in a clear, specific, and measurable manner?; Q2: Were the perspective of the analysis (societal, third-party payer, etc.) and reasons for its selection stated?; Q3: Were variable estimates used in the analysis from the best available source (i.e., randomized control trial—best, expert opinion—worst)?; Q4: If estimates came from a subgroup analysis, were the groups prespecified at the beginning of the study?; Q5: Was uncertainty handled by (1) statistical analysis to address random events, (2) sensitivity analysis to cover a range of assumptions?; Q6: Was incremental analysis performed between alternatives for resources and costs?; Q7: Was the methodology for data abstraction (including the value of health states and other benefits) stated?; Q8: Did the analytic horizon allow time for all relevant and important outcomes? Were benefits and costs that went beyond 1 year discounted (3–5 %) and justification given for the discount rate?; Q9: Was the measurement of costs appropriate and the methodology for the estimation of quantities and unit costs clearly described?; Q10: Were the primary outcome measure(s) for the economic evaluation clearly stated and did they include the major short-term, long-term and negative outcomes included? Was justification given for the measures/scales used?; Q11: Were the health outcomes measures/scales valid and reliable? If previously tested valid and reliable measures were not available, was justification given for the measures/scales used?; Q12: Were the economic model (including structure), study methods and analysis, and the components of the numerator and denominator displayed in a clear, transparent manner?; Q13: Were the choice of economic model, main assumptions, and limitations of the study stated and justified?; Q14: Did the author(s) explicitly discuss direction and magnitude of potential biases?; Q15: Were the conclusions/recommendations of the study justified and based on the study results?; Q16: Was there a statement disclosing the source of funding for the study?