Changing patterns in long-acting bronchodilator trials in chronic obstructive pulmonary disease

Abstract

James F Donohue1, Paul W Jones21Division of Pulmonary Disease and Critical Care Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2St. George's, University of London, London, UKAbstract: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Developments in the understanding of COPD have led to standard guidelines for diagnosis, treatment, and spirometry assessments, which have in turn influenced trial designs and inclusion criteria. Substantial clinical evidence has been gained from clinical trials and supports a positive approach to COPD management. However, there appear to be changing trends in recent trials. Large bronchodilator studies have reported lower improvements in trough forced expiratory volume in 1 second (FEV1) values versus placebo than were observed in earlier studies, while the rate of FEV1 decline seems to be lower in more recent trials. In addition, recent evidence has called into question the usefulness of bronchodilator reversibility testing as a trial inclusion criterion. Baseline patient populations and use of concomitant medications have also changed over recent years due to increased treatment options. The impact of these many variables on clinical trial results is explored, with a particular focus on changes in inclusion criteria and patient baseline demographics.Keywords: chronic obstructive pulmonary disease, clinical trials, forced expiratory volume in 1 second, long-acting bronchodilators, lung function