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A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults.

ABSTRACT: Bronchiectasis is an increasing clinical problem, but multiple recent clinical trials have failed to reach their primary end-point. Difficulties in achieving "positive" bronchiectasis trials is reflected in a lack of agreement from trialists and regulators on what are the optimal end-points.To evaluate the use of end-points in bronchiectasis trials, we conducted a systematic review of published bronchiectasis trials from 2008 to 2018 and extracted end-points used, definitions, methods of analysis and responsiveness.Our analysis shows that quality of life and exacerbation end-points are most frequently used. Trials using exacerbation end-points have been characterised by varying definitions, multiple methods of analysis and durations of follow-up. There are multiple quality of life tools for bronchiectasis (Quality of Life - Bronchiectasis questionnaire, St George's Respiratory Questionnaire, etc.). The majority of studies measure lung function (e.g. forced expiratory volume in 1 s), but this is shown to be nonresponsive to the majority of interventions. Microbiology end-points frequently show statistically significant differences in phase 2 antibiotic studies but their correlation with clinical end-points is unknown.This systematic review demonstrates a need for guidance to standardise definitions and design features to improve reproducibility and increase the likelihood of demonstrating statistically significant benefits with new therapies.

SUBMITTER: Crichton ML

PROVIDER: S-EPMC9488648 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults.

Crichton Megan L ML Aliberti Stefano S Chalmers James D JD

European respiratory review : an official journal of the European Respiratory Society 20190314 151

Bronchiectasis is an increasing clinical problem, but multiple recent clinical trials have failed to reach their primary end-point. Difficulties in achieving "positive" bronchiectasis trials is reflected in a lack of agreement from trialists and regulators on what are the optimal end-points.To evaluate the use of end-points in bronchiectasis trials, we conducted a systematic review of published bronchiectasis trials from 2008 to 2018 and extracted end-points used, definitions, methods of analysi ...[more]

PMID: 30872400

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A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults.

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A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults.

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