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

Megan L. Crichton, Stefano Aliberti, James D. Chalmers (Lead / Corresponding author)

Research output: Contribution to journalReview article

2 Citations (Scopus)
50 Downloads (Pure)

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 languageEnglish
Article number180108
Pages (from-to)1-14
Number of pages14
JournalEuropean Respiratory Review
Volume28
Issue number151
Early online date14 Mar 2019
DOIs
Publication statusPublished - 31 Mar 2019

Fingerprint

Bronchiectasis
Clinical Trials
Quality of Life
Forced Expiratory Volume
Microbiology
Anti-Bacterial Agents
Lung

Keywords

  • Bronchiectasis/diagnosis
  • Clinical Trials as Topic/methods
  • Disease Progression
  • Endpoint Determination/standards
  • Humans
  • Lung/drug effects
  • Quality of Life
  • Recovery of Function
  • Research Design/standards
  • Respiratory System Agents/adverse effects
  • Treatment Outcome

Cite this

@article{314eff45026b4ea1b560919c44f7bf99,
title = "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.",
keywords = "Bronchiectasis/diagnosis, Clinical Trials as Topic/methods, Disease Progression, Endpoint Determination/standards, Humans, Lung/drug effects, Quality of Life, Recovery of Function, Research Design/standards, Respiratory System Agents/adverse effects, Treatment Outcome",
author = "Crichton, {Megan L.} and Stefano Aliberti and Chalmers, {James D.}",
note = "Copyright {\circledC}ERS 2019.",
year = "2019",
month = "3",
day = "31",
doi = "10.1183/16000617.0108-2018",
language = "English",
volume = "28",
pages = "1--14",
journal = "European Respiratory Review",
issn = "0905-9180",
publisher = "European Respiratory Society",
number = "151",

}

A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults. / Crichton, Megan L.; Aliberti, Stefano; Chalmers, James D. (Lead / Corresponding author).

In: European Respiratory Review, Vol. 28, No. 151, 180108, 31.03.2019, p. 1-14.

Research output: Contribution to journalReview 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.

N1 - Copyright ©ERS 2019.

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.

KW - Bronchiectasis/diagnosis

KW - Clinical Trials as Topic/methods

KW - Disease Progression

KW - Endpoint Determination/standards

KW - Humans

KW - Lung/drug effects

KW - Quality of Life

KW - Recovery of Function

KW - Research Design/standards

KW - Respiratory System Agents/adverse effects

KW - Treatment Outcome

U2 - 10.1183/16000617.0108-2018

DO - 10.1183/16000617.0108-2018

M3 - Review article

VL - 28

SP - 1

EP - 14

JO - European Respiratory Review

JF - European Respiratory Review

SN - 0905-9180

IS - 151

M1 - 180108

ER -