Adjudication of exacerbations in bronchiectasis using modified EMBARC criteria in the CLEAR Trial.

Abstract

Introduction: The EMBARC consensus criteria can be used to identify and categorise pulmonary exacerbations (PEs) in clinical trials. This paper describes methods used to independently adjudicate PEs using modified EMBARC criteria in a large multicentre bronchiectasis trial (CLEAR ISRCTN89040295).

Methods: The Respiratory and Systemic Symptoms Questionnaire was used to objectively collect signs and symptoms at the onset of a PE. A mEMBARC PE was defined as ≥3 symptoms, with symptoms present for ≥48 h and prescription of an antibiotic. Individual sites recorded antibiotic use for PEs. An adjudication panel independently adjudicated and then agreed on PEs according to mEMBARC criteria. Data required to determine PEs using modified Fuchs criteria was also collected.

Results: Sites reported 462 PEs from 203 patients reported in the CLEAR trial. The adjudication panel categorised these exacerbations as: 239 out of 462 (52%) fully qualifying mEMBARC PEs (meeting all mEMBARC criteria), 32 out of 462 (7%) partially qualifying mEMBARC PEs (≤3 symptoms present for ≥48 h or ≥3 symptoms present for <48 h and antibiotics prescribed) and 191 out of 462 (41%) non-mEMBARC PEs (antibiotics prescribed but symptoms and duration not met). When data were classified using modified Fuchs criteria a sensitivity analysis produced results that were consistent with the main trial results.

Conclusion: PEs are increasingly used as the primary outcome in bronchiectasis trials, making accuracy in their identification essential. More rigorous capture of exacerbation symptoms and implementation of a standardised and reproducible decision-making process, supported by an independent adjudication panel, is important for capturing PEs and ensuring the integrity of trial outcomes.