TY - JOUR
T1 - Opportunities for improved clinical trial designs in acute respiratory distress syndrome
AU - Wick, Katherine D.
AU - Aggarwal, Neil R.
AU - Curley, Martha A.Q.
AU - Fowler, Alpha A.
AU - Jaber, Samir
AU - Kostrubiec, Maciej
AU - Lassau, Nathalie
AU - Laterre, Pierre François
AU - Lebreton, Guillaume
AU - Levitt, Joseph E.
AU - Mebazaa, Alexandre
AU - Rubin, Eileen
AU - Sinha, Pratik
AU - Ware, Lorraine B.
AU - Matthay, Michael A.
N1 - Funding Information:
Major funding for ARDS trials in the USA began in 1994 with ARDSNet, leading to several landmark trials that still guide the fundamental supportive management of ARDS patients. 32,77,78 The PETAL Network then prioritised the identification of early interventions for patients at risk of ARDS or with early disease, and has been pivotal to the research effort during the COVID-19 pandemic. On March 17, 2021, the US National Institutes of Health (NIH) announced a research initiative to comprehensively, prospectively phenotype patients with ARDS, pneumonia, and sepsis (the APS Consortium), supported by NHLBI and the National Institute for General Medical Sciences. 79 The focus of this funding initiative is to comprehensively characterise the biological, imaging, and clinical characteristics of 5000 patients with critical illness syndromes, with 1 year of follow-up to allow study of longer-term health consequences of ARDS. This initiative will be valuable in achieving better understanding of enrichment opportunities for future trials and in identifying meaningful endpoints beyond mortality.
Funding Information:
The 2021 Critical Care Clinical Trialists (3CT) Workshop received unrestricted funding from Abbott Diagnostics and AM-Pharma to partially cover travel and lodging costs, when necessary, but no further payments were made to participants. These organisations had no role in the scientific programme for the conference; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. KDW acknowledges grant support from the US National Institutes of Health (NIH 5T32GM008440–24). NRA receives funds from the NIH–National Heart, Lung, and Blood Institute (NHLBI) PETAL Network. LBW receives research grant support from NIH HL103836, HL126176, and HL158906; and grant support from the US Department of Defense. MAM receives research grant support from NIH HL134828, HL126456, HL140026, and 143896; and grant support from the US Department of Defense. We appreciate the thoughtful input of Lora A Reineck (NHLBI, NIH, Bethesda, MA, USA) to the review of this manuscript, and acknowledge her contribution to this important field of generating new approaches to clinical trial designs in ARDS. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of NHLBI, NIH, or the US Department of Health and Human Services. Figure 2 and 3 created with BioRender.com.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85137081803&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(22)00294-6
DO - 10.1016/S2213-2600(22)00294-6
M3 - Review article
C2 - 36057279
AN - SCOPUS:85137081803
VL - 10
SP - 916
EP - 924
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
SN - 2213-2600
IS - 9
ER -