Opportunities for improved clinical trial designs in acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is a common critical illness syndrome with high morbidity and mortality. There are no proven pharmacological therapies for ARDS. The current definition of ARDS is based on shared clinical characteristics but does not capture the heterogeneity in clinical risk factors, imaging characteristics, physiology, timing of onset and trajectory, and biology of the syndrome. There is increasing interest within the ARDS clinical trialist community to design clinical trials that reduce heterogeneity in the trial population. This effort must be balanced with ongoing work to craft an inclusive, global definition of ARDS, with important implications for trial design. Ultimately, the two aims-to design trials that are applicable to the diverse global ARDS population while also advancing opportunities to identify targetable traits-should coexist. In this Personal View, we recommend two primary strategies to improve future ARDS trials: the development of new methods to target treatable traits in clinical trial populations, and improvements in the representativeness of ARDS trials, with the inclusion of global populations. We emphasise that these two strategies are complementary. We also discuss how a proposed expansion of the definition of ARDS could affect the future of clinical trials.
Competing Interests: Declaration of interests SJ receives consulting fees from Drager, Fisher-Paykel, Medtronic, Mindray, and Baxter. NL receives grant funding from Guerbet. GL receives consulting fees from Abbott, Abiomed, and Baxter; and speaking fees from LivaNova. AM receives grants from 4TEEN4, Abbott, Roche, and Sphyngotec; and consulting fees from Orion, Roche, Adrenomed, and Fire1. AM participates on the data and safety monitoring board for Roche. LBW declares grants from Genentech, Boehringer Ingelheim, and CSL Behring, outside the submitted work; and consulting fees from Foresee, Merck, Citius Pharmaceuticals, Quark, and Boehringer Ingelheim. MAM declares grant support from Roche-Genentech for ARDS observational studies; and consulting income from Citius Pharmaceuticals, Johnson & Johnson, Gilead Pharmaceuticals, Plant Therapeutics, and Novartis Pharmaceuticals, outside the submitted work. All other authors declare no competing interests.
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