TY - JOUR
T1 - Randomised controlled trials in severe asthma
T2 - Selection by phenotype or stereotype
AU - Wessex Severe Asthma Cohort
AU - Brown, Thomas
AU - Jones, Thomas
AU - Gove, Kerry
AU - Barber, Clair
AU - Elliott, Scott
AU - Chauhan, Anoop
AU - Howarth, Peter
AU - Aitkin, L.
AU - Babu, S.
AU - Dennison, P.
AU - Djukanovic, R.
AU - Grainge, C.
AU - Hewitt, L.
AU - Jayasekera, N.
AU - Kurukulaaratchy, R.
AU - Kerley, S.
AU - Lau, L.
AU - Laws, D.
AU - Owen, J.
AU - Ray, E.
AU - Reynish, D.
AU - Rupani, H.
AU - Scullion-Win, O.
N1 - Funding Information:
This work was funded by Research Councils UK: Medical Research Council (MRC; G0800649). Funding information for this article has been deposited with the Crossref Funder Registry.
Funding Information:
Support statement: This work was funded by Research Councils UK: Medical Research Council (MRC; G0800649). Funding information for this article has been deposited with the Crossref Funder Registry.
Funding Information:
All participants underwent a detailed characterisation protocol including clinical, physiological and biological assessments (full details are included in the supplementary material). The study was funded by the UK Medical Research Council (MRC)/National Institute for Health Research (NIHR) Patient Research Cohorts Initiative and was conducted in accordance with the International Conference on Harmonisation and Good Clinical Practice standards and the ethical principles outlined in the Declaration of Helsinki. Independent ethics committee approval was obtained (MREC No. 09/H0502/37) and all participants provided written, informed consent prior to participation in the study.
Funding Information:
Conflict of interest: T. Brown reports personal fees from Teva, Chiesi Farmaceutici, Novartis and Napp, and nonfinancial support from AstraZeneca, outside the submitted work. T. Jones reports non-financial support from Teva, personal fees and non-financial support from Chiesi Farmaceutici, outside the submitted work. K. Gove has nothing to disclose. C. Barber has nothing to disclose. S. Elliott has nothing to disclose. A. Chauhan reports personal fees and non-financial support from Teva, non-financial support from Boehringer Ingelheim, and personal fees from AstraZeneca, outside the submitted work. P. Howarth reports grants from the Medical Research Council, during the conduct of the study; and is a part-time employee of GlaxoSmithKline.
Publisher Copyright:
Copyright ©ERS 2018
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma. Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000. 37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5-17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2-86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies. Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.
AB - Previous publications have highlighted the disparity between research trial populations and those in clinical practice, but it has not been established how this relates to randomised controlled trials (RCTs) of phenotype-targeted biological therapies in severe asthma. Detailed characterisation data for 342 severe asthma patients within the Wessex Severe Asthma Cohort (WSAC) was compared against comprehensive trial eligibility criteria for published phase IIB and phase III RCTs evaluating biological therapies in severe asthma since 2000. 37 RCTs evaluating 20 biological therapies were identified. Only a median of 9.8% (range 3.5-17.5%) of severe asthma patients were found to be eligible for enrolment in the phase III trials. Stipulations for airflow obstruction, bronchodilator reversibility and smoking history excluded significant numbers of patients. A median of 78.9% (range 73.2-86.6%) of patients with severe eosinophilic asthma would have been excluded from participation in the phase III licensing trials of interleukin (IL)-5/IL-5R targeted therapies. Despite including only well characterised and optimally treated severe asthmatics under specialist care within the WSAC study, the vast majority were excluded from trial participation by criteria designed to re-confirm diagnostic labels rather than by biomarker criteria that predict the characteristic addressed by the treatment.
KW - RCUK
KW - MRC
UR - http://www.scopus.com/inward/record.url?scp=85058609680&partnerID=8YFLogxK
U2 - 10.1183/13993003.01444-2018
DO - 10.1183/13993003.01444-2018
M3 - Article
C2 - 30361247
AN - SCOPUS:85058609680
SN - 0903-1936
VL - 52
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 6
M1 - 1801444
ER -