Observational studies of inhaled corticosteroid effectiveness in COPD: Lessons learned.

Research paper by Samy S Suissa, Pierre P Ernst

Indexed on: 22 Apr '18Published on: 22 Apr '18Published in: CHEST®


Randomized controlled trials at times investigate findings suggested by observational studies. For example, the TORCH trial, which did not show a mortality reduction with inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD), was motivated by some observational studies that suggested considerable reductions in mortality with these drugs. Reasons for these discrepancies are unclear. We searched the literature to identify all observational studies, including cohort and case-control studies, investigating the effectiveness of ICS on major outcomes in COPD patients, including death and hospitalization for COPD. We identified 21 studies and found that nine studies were affected by immortal time bias, five by immeasurable time bias, and seven by the "asthma factor" bias, with some studies by more than one bias. These studies found important reductions in the rates of major COPD outcomes with ICS use, with pooled rate ratios of 0.71 (95% CI 0.67-0.76), 0.76 (95% CI 0.70-0.83) and 0.79 (95% CI 0.73-0.87) respectively for the three sources of bias. In contrast, the five studies unaffected by these major biases did not find an association (pooled rate ratio 1.02; 95% CI: 0.88-1.17). Observational studies are important to provide evidence from real-world data on medication effects. However, appropriate study design and analysis are essential to avoid biases and ensure randomized trials with greater chances of success. The observational studies suggesting potential beneficial effects of non-respiratory drugs to treat COPD, such as statins and beta-blockers, will also need careful review before embarking on long and expensive randomized trials. Copyright © 2018. Published by Elsevier Inc.