Megatrials for bronchodilators in chronic obstructive pulmonary disease (COPD) treatment: Time to reflect

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. Although (long-acting) bronchodilators are used to relieve symptoms, the impact of bronchodilators on COPD mortality remains an unresolved issue. Our aim was to explore the results and the interpretations of the results of studies of bronchodilator treatment from high-impact COPD trials. Methods: We searched PubMed and Embase for primary publications of randomized controlled trials with more than 1000 participants with COPD and that studied the effectiveness of long-acting bronchodilator treatment. We assessed population characteristics, primary outcomes, focus of outcomes, and possible bias from concomitant pulmonary medication. Results: We retrieved 5 primary publications of large trials. Participants tended to be patients with rather severe COPD who were cared for at a hospital. Only half of the primary outcomes were statistically significant. Reports tended to focus on statically significant outcomes and not necessarily on primary outcomes or outcomes of the whole study population. The relevance of study outcomes was rarely discussed. Discussion: The rather small effects of bronchodilators in a COPD population that is not representative for daily care, together with the tendency of relying on statistical rather than clinical significance, hampers translation to the large number of patients with COPD in the community.