International Differences in the Frequency of Chronic Obstructive Pulmonary Disease Exacerbations Reported in Three Clinical Trials

Calverley, Peter MA, Martinez, Fernando J, Vestbo, Jorgen, Jenkins, Christine R, Wise, Robert, Lipson, David A, Cowans, Nicholas J, Yates, Julie, Crim, Courtney and Celli, Bartolome R (2022) International Differences in the Frequency of Chronic Obstructive Pulmonary Disease Exacerbations Reported in Three Clinical Trials. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 206 (1). pp. 25-33.

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Official URL: http://dx.doi.org/10.1164/rccm.202111-2630oc

Abstract

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, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution. Measurements and Main Results: For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was two- to threefold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrollment. Of the 18 countries contributing to all trials, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across trials. Severe exacerbations showed a different rank order internationally. Conclusions: Countries contributing to COPD trials differ consistently in their reporting of healthcare-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.

Item Type:	Article
Uncontrolled Keywords:	chronic obstructive pulmonary disease, exacerbations, bronchodilators, inhaled corticosteroids
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	04 Nov 2022 15:37
Last Modified:	16 Mar 2024 02:39
DOI:	10.1164/rccm.202111-2630OC
Open Access URL:	https://doi.org/10.1164/rccm.202111-2630OC
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3166007