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Rationale Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries. Objectives We investigated whether systematic differences in national exacerbation rates might explain this observed variation. Methods We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of COPD, c