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Review
. 2020 Dec;46(12):2153-2156.
doi: 10.1007/s00134-020-06232-x. Epub 2020 Nov 2.

Designing an ARDS trial for 2020 and beyond: focus on enrichment strategies

Lorraine B Ware  1 , Michael A Matthay  2 , Alexandre Mebazaa  3
Affiliations
Review

Designing an ARDS trial for 2020 and beyond: focus on enrichment strategies

Lorraine B Ware et al. Intensive Care Med. 2020 Dec.

Abstract

With the exception of a few successes in trials of supportive care, the majority of interventional clinical trials for acute respiratory distress syndrome (ARDS) have not led to new therapies. To improve the likelihood of benefit from clinical trial interventions in ARDS, clinical trial design must be improved. To optimize trial design, many factors need to be considered including the type of therapy to be tested, the type of trial (phase 2 or 3), how patients will be selected, primary and secondary end-points, and strategy for conduct of the trial, including potential newer trial designs such as platform or adaptive trials. Of these, optimization of patient selection is central to the likelihood of success and is particularly relevant in ARDS, which is a heterogeneous clinical syndrome, not a homogeneous disease. Recent advances including improved understanding of pathophysiologic mechanisms and better tools for outcome prediction in ARDS should facilitate both predictive and prognostic enrichment. This commentary focuses on new information and novel methods for prognostic and predictive enrichment that may be useful to optimize patient selection and increase the likelihood of positive clinical trials in ARDS.

Keywords: Acute lung injury; Acute respiratory distress syndrome; Clinical trial; Pathophysiology; Predictive enrichment; Prognostic enrichment.

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Conflict of interest statement

Dr. Ware reports personal fees from Bayer, CSL Behring, Quark, Merck, Citius, Foresee and Boehringer Ingelheim and research contracts with Genentech and CSL Behring, all outside the submitted work. Dr. Mebazaa reports personal fees from Orion, Servier, Otsuka, Philips, Sanofi, Adrenomed, Epygon and Fire 1 and grants and personal fees from 4TEEN4, Abbott and Sphyngotec, outside the submitted work. Dr. Matthay reports research contracts from Bayer and Roche-Genentech outside the submitted work.

Figures

Fig. 1
Fig. 1
Potential benefits, challenges and risks of different enrichment strategies for clinical trials in ARDS
See this image and copyright information in PMC

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