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Review
. 2011 Jan 7:6:35-45.
doi: 10.2147/COPD.S14680.

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

James F Donohue  1 , Paul W Jones
Affiliations
Review

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

James F Donohue et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

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 (FEV(1)) values versus placebo than were observed in earlier studies, while the rate of FEV(1) 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.

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Figures

Figure 1
Figure 1
Treatment effect with tiotropium (left-hand axis) and baseline FEV1 (right-hand axis) against study publication date (Donohue et al, Casaburi et al (treatment effect results reported as a range), Brusasco et al, Niewoehner et al, Dusser et al, Chan et al, Tonnel et al, and Tashkin et al (treatment effect results reported as a range). Abbreviation: FEV1, forced expiratory volume in 1 second.
Figure 2
Figure 2
Rate of FEV1 decline in the placebo arm of long-term COPD studies.,,– Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second.
Figure 3
Figure 3
Response to inhaled corticosteroid (fluticasone propionate) + long-acting β2-agonist (salmeterol) in reversible and nonreversible patients in COPD., Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid.
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References

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