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Large trials, new knowledge: the changing face of COPD management. Large, well-designed, drug-treatment trials have allowed useful advances to be made in the treatment and diagnosis of chronic obstructive pulmonary disease (COPD). The two main clinical trial designs that provide evidence of effectiveness are randomised controlled trials (RCTs) and observational studies. RCTs are generally considered to provide more robust evidence than that obtained from observational studies and can generate informative secondary analyses in addition to the primary research query. In COPD, however, well-designed comparator-controlled RCTs, although successful, have been shown to have some limitations, such as a lack of generalisability. The findings of observational studies, whilst prone to bias, can generate valuable data and have also provided useful information relating to the efficacy of treatments in the current COPD management guidelines. This review focuses on major COPD studies published since 2007 (including UPLIFT, TIOSPIR, ECLIPSE and COPDGene), and assesses the influence such RCTs and large observational studies have had on our knowledge of COPD, and how these may impact future trial designs.