Precision Medicine and Heterogeneity of Treatment Effect in Therapies for ARDS

Yasin A Khan¹, Eddy Fan², Niall D Ferguson³

Affiliations

¹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
² Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, Toronto, ON, Canada; Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada.
³ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, Toronto, ON, Canada; Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada. Electronic address: n.ferguson@utoronto.ca.

PMID: 34270967
PMCID: PMC8277554
DOI: 10.1016/j.chest.2021.07.009

Review

Precision Medicine and Heterogeneity of Treatment Effect in Therapies for ARDS

Yasin A Khan et al. Chest. 2021 Nov.

. 2021 Nov;160(5):1729-1738.

doi: 10.1016/j.chest.2021.07.009. Epub 2021 Jul 14.

Authors

Yasin A Khan¹, Eddy Fan², Niall D Ferguson³

Affiliations

¹ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
² Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, Toronto, ON, Canada; Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada.
³ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, Toronto, ON, Canada; Division of Respirology, Department of Medicine, University Health Network, Toronto, ON, Canada. Electronic address: n.ferguson@utoronto.ca.

PMID: 34270967
PMCID: PMC8277554
DOI: 10.1016/j.chest.2021.07.009

Abstract

ARDS is a clinically heterogeneous syndrome, rather than a distinct disease. This heterogeneity at least partially explains the difficulty in studying treatments for these patients and contributes to the numerous trials of therapies for the syndrome that have not shown benefit. Recent studies have identified different subphenotypes within the heterogeneous patient population. These different subphenotypes likely have variable clinical responses to specific therapies, a concept known as heterogeneity of treatment effect. Recognizing different subphenotypes and heterogeneity of treatment effect has important implications for the clinical management of patients with ARDS. This review presents studies that have identified different subphenotypes and discusses how they can modify the effects of therapies evaluated in trials that are commonly considered to have shown no overall benefit in patients with ARDS.

Keywords: ARDS; acute respiratory failure; heterogeneity of treatment effect.

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Figures

**Figure 1**
A potential algorithm outlining different subphenotypes of patients with ARDS and specific therapeutic considerations based on effect modification among these subphenotypes. ΔP = driving pressure; HFOV = high-frequency oscillatory ventilation; HTE = heterogeneity of treatment effect; NMBA = neuromuscular blocking agents; PEEP = positive end-expiratory pressure.

See this image and copyright information in PMC

References

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Precision Medicine and Heterogeneity of Treatment Effect in Therapies for ARDS

Affiliations

Precision Medicine and Heterogeneity of Treatment Effect in Therapies for ARDS

Authors

Affiliations

Abstract

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References

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Full Text Sources