Exacerbation outcome definitions in clinical trials of COPD interventions: a systematic review

Abstract

Introduction: In clinical trials of COPD interventions, the underlying definition of an “exacerbation” as a measured outcome remains inconsistent and unstandardised. This study reviews published clinical trials to describe how these medical events are defined as trial outcomes.

Method: Journal articles describing the results of clinical trials with ≥100 enrolled participants published from 1995-2020 were identified from the Cochrane Central Register of Controlled Trials and reviewed for inclusion in the study.

Results: A search of 7586 results provided 243 eligible publications describing the results of 254 trials. Exacerbation definitions (n=176) were classified by their constituent attributes: symptom (n=54), treatment (n=13), hybrids of the former two groups (n=109); and undefined (n=70). Heterogeneity was observed across all types of definition (Table 1). Exacerbation severity algorithms showed varying definitions for mild events. Moderate events (n=90) were consistently defined by systemic corticosteroid and/or antibiotic usage (n=71), and severe events (n=97) by hospital admission (n=96).

Conclusion: Definitions of an “exacerbation” of COPD in clinical trials are heterogenous. This impacts how data are interpreted, compared and later implemented in clinical recommendations and practice. Further work is needed to reach consensus on how these consequential events should be defined and measured in clinical trials.