Building an international precision medicine platform trial for the acute respiratory distress syndrome (ARDS): an expert consensus project report
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Almost all large-scale trials of disease-modifying therapeutic agents in critical care have failed to show benefit for patients, which may be explained in part by the clinical and biological heterogeneity inherent in virtually all critical illness syndromes. Enrichment strategies have been developed to separate responders from non-responders and better target treatments. In patients with the acute respiratory distress syndrome, a critical illness syndrome involving severe lung inflammation, latent class analysis and other clustering approaches have led to the discovery of subgroups (phenotypes) that appear to respond differently to treatment based on retrospective analyses of published clinical trials and observational cohorts. The next step is to test these phenotypes in a prospective trial. Rapid, point-of-care analytical methods have now made such a trial possible. There is a need to advance treatment for patients with acute respiratory distress syndrome and other critical illness syndromes by incorporating a phenotype-based approach into prospective trial design. The hyperinflammatory and hypoinflammatory phenotypes, that have been identified in acute respiratory distress syndrome, will be the first to be included in such a trial, with scope for further phenotypes to be studied over time.
Future work
This Efficacy and Mechanism Evaluation report, through expert consensus, describes a new Phase II, multiarm, adaptive platform randomised controlled trial design that tests multiple pharmacological therapies in a population of patients with acute respiratory distress syndrome stratified by baseline inflammatory phenotype. This report also reviews issues to be considered in developing precision medicine trials in critical care, which are designed with newly developed clinical phenotypes in mind. This work has been used to develop the Precision medicine Adaptive Network platform Trial in Hypoxaemic acutE respiratory failuRe precision medicine trial in acute respiratory distress syndrome, which has been funded and will begin recruitment in June 2025.
Limitations
This report is the result of expert consensus review, rather than utilising strict review methodologies (e.g. Delphi consensus process). However, expert consensus has been found to generate similar results to consensus processes when a high degree of agreement is reached and > 70% agreement was reached for all included recommendations.
Funding
This article presents independent research funded by the (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR154493.
Almost all large-scale trials of disease-modifying therapeutic agents in critical care have failed to show benefit for patients, which may be explained in part by the clinical and biological heterogeneity inherent in virtually all critical illness syndromes. Enrichment strategies have been developed to separate responders from non-responders and better target treatments. In patients with the acute respiratory distress syndrome, a critical illness syndrome involving severe lung inflammation, latent class analysis and other clustering approaches have led to the discovery of subgroups (phenotypes) that appear to respond differently to treatment based on retrospective analyses of published clinical trials and observational cohorts. The next step is to test these phenotypes in a prospective trial. Rapid, point-of-care analytical methods have now made such a trial possible. There is a need to advance treatment for patients with acute respiratory distress syndrome and other critical illness syndromes by incorporating a phenotype-based approach into prospective trial design. The hyperinflammatory and hypoinflammatory phenotypes, that have been identified in acute respiratory distress syndrome, will be the first to be included in such a trial, with scope for further phenotypes to be studied over time.
Future work
This Efficacy and Mechanism Evaluation report, through expert consensus, describes a new Phase II, multiarm, adaptive platform randomised controlled trial design that tests multiple pharmacological therapies in a population of patients with acute respiratory distress syndrome stratified by baseline inflammatory phenotype. This report also reviews issues to be considered in developing precision medicine trials in critical care, which are designed with newly developed clinical phenotypes in mind. This work has been used to develop the Precision medicine Adaptive Network platform Trial in Hypoxaemic acutE respiratory failuRe precision medicine trial in acute respiratory distress syndrome, which has been funded and will begin recruitment in June 2025.
Limitations
This report is the result of expert consensus review, rather than utilising strict review methodologies (e.g. Delphi consensus process). However, expert consensus has been found to generate similar results to consensus processes when a high degree of agreement is reached and > 70% agreement was reached for all included recommendations.
Funding
This article presents independent research funded by the (NIHR) Efficacy and Mechanism Evaluation programme as award number NIHR154493.
Date Issued
2025-07-01
Date Acceptance
2025-02-01
Citation
Efficacy and Mechanism Evaluation, 2025, 2025, pp.1-43
ISSN
2050-4365
Publisher
NIHR Journals Library
Start Page
1
End Page
43
Journal / Book Title
Efficacy and Mechanism Evaluation
Volume
2025
Copyright Statement
Copyright © 2025 Reddy et al. This work was produced by Reddy et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.
License URL
Identifier
10.3310/TTND8896
Publication Status
Published
Date Publish Online
2025-07-01