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.
| Original language | English |
|---|---|
| Article number | 180108 |
| Journal | European Respiratory Review |
| Volume | 28 |
| Issue number | 151 |
| DOIs | |
| Publication status | Published - Mar 31 2019 |
Fingerprint
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults. / Crichton, Megan L.; Aliberti, Stefano; Chalmers, James D.
In: European Respiratory Review, Vol. 28, No. 151, 180108, 31.03.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults
AU - Crichton, Megan L.
AU - Aliberti, Stefano
AU - Chalmers, James D.
PY - 2019/3/31
Y1 - 2019/3/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062970256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062970256&partnerID=8YFLogxK
U2 - 10.1183/16000617.0108-2018
DO - 10.1183/16000617.0108-2018
M3 - Review article
C2 - 30872400
AN - SCOPUS:85062970256
VL - 28
JO - European Respiratory Review
JF - European Respiratory Review
SN - 0905-9180
IS - 151
M1 - 180108
ER -