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.
Abstract
There is an urgent need to standardise clinical trial end-points in bronchiectasis. This systematic review shows the diversity of end-points used in bronchiectasis and suggests approaches that may improve the success rate and reproducibility of trials. http://ow.ly/d4HR30nvvS3
Footnotes
This study is registered with PROSPERO (www.crd.york.ac.uk/prospero) with identifier number CRD42018106167.
Provenance: Submitted article, peer reviewed.
Conflict of interest: M.L. Crichton has nothing to disclose.
Conflict of interest: S. Aliberti has nothing to disclose.
Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline (research grants for COPD), grants and personal fees from Boehringer-Ingelheim (research grants for COPD studies), grants from AstraZeneca (research grants for COPD), grants and personal fees from Pfizer (research grants for COPD), grants and personal fees from Bayer Healthcare (research into bronchiectasis), grants and personal fees from Grifols (research into bronchiectasis), personal fees from Napp (consulting), personal fees from Aradigm corporation (consulting), and grants and personal fees from Insmed, outside the submitted work.
Support statement: EMBARC2 is supported by the European Respiratory Society through the Clinical Research Collaboration. The project is supported by project partners: Chiesi, Grifols, Insmed, Novartis and Zambon. EMBARC is supported by EU/EFPIA IMI iABC grant agreement no. 115721. J.D. Chalmers is supported by the GSK/British Lung Foundation Chair of Respiratory Research. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received December 4, 2018.
- Accepted January 23, 2019.
- Copyright ©ERS 2019.
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