The generalizability of bronchiectasis randomized controlled trials: A multicentre cohort study.

Area of Science:

• Pulmonary Medicine
• Clinical Research Methodology
• Epidemiology

Background:

• Randomized controlled trials (RCTs) in bronchiectasis face challenges in patient recruitment and achieving efficacy endpoints.
• Assessing the generalizability of RCT findings to the broader bronchiectasis population is crucial for clinical practice.

Purpose of the Study:

• To evaluate the representativeness of patients included in major bronchiectasis RCTs.
• To compare the characteristics and outcomes of patients eligible versus ineligible for RCTs across European cohorts.

Main Methods:

• Eligibility criteria from 10 major bronchiectasis RCTs were applied to 6 observational European cohorts.
• Demographics and clinical outcomes were analyzed for eligible and ineligible patient groups.

Main Results:

• Only a small fraction of patients were eligible for specific RCTs (e.g., 33% for macrolide trials, 15% for inhaled antibiotic trials).
• Eligible patients were often more severe, with higher mortality and exacerbation rates.
• However, the majority of adverse events (deaths, exacerbations) occurred in the larger group of ineligible patients.

Conclusions:

• Patients enrolled in bronchiectasis RCTs are not fully representative of the general patient population.
• The majority of bronchiectasis morbidity and mortality occurs in patients excluded from many current clinical trials, highlighting a gap in research generalizability.