학술논문
Development and External Validation of Models to Predict Persistent Hypoxemic Respiratory Failure for Clinical Trial Enrichment.
Document Type
Academic Journal
Author
Sathe NA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Zelnick LR; Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA.; Morrell ED; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Bhatraju PK; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Sepsis Center of Research Excellence, University of Washington, Seattle, WA.; Kerchberger VE; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.; Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN.; Hough CL; Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Oregon Health & Science University, Portland, OR.; Ware LB; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN.; Fohner AE; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.; Wurfel MM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA.; Sepsis Center of Research Excellence, University of Washington, Seattle, WA.
Source
Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0355501 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0293 (Electronic) Linking ISSN: 00903493 NLM ISO Abbreviation: Crit Care Med Subsets: MEDLINE
Subject
Language
English
Abstract
Objectives: Improving the efficiency of clinical trials in acute hypoxemic respiratory failure (HRF) depends on enrichment strategies that minimize enrollment of patients who quickly resolve with existing care and focus on patients at high risk for persistent HRF. We aimed to develop parsimonious models predicting risk of persistent HRF using routine data from ICU admission and select research immune biomarkers.
Design: Prospective cohorts for derivation ( n = 630) and external validation ( n = 511).
Setting: Medical and surgical ICUs at two U.S. medical centers.
Patients: Adults with acute HRF defined as new invasive mechanical ventilation (IMV) and hypoxemia on the first calendar day after ICU admission.
Interventions: None.
Measurements and Main Results: We evaluated discrimination, calibration, and practical utility of models predicting persistent HRF risk (defined as ongoing IMV and hypoxemia on the third calendar day after admission): 1) a clinical model with least absolute shrinkage and selection operator (LASSO) selecting Pa o2 /F io2 , vasopressors, mean arterial pressure, bicarbonate, and acute respiratory distress syndrome as predictors; 2) a model adding interleukin-6 (IL-6) to clinical predictors; and 3) a comparator model with Pa o2 /F io2 alone, representing an existing strategy for enrichment. Forty-nine percent and 69% of patients had persistent HRF in derivation and validation sets, respectively. In validation, both LASSO (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.64-0.73) and LASSO + IL-6 (0.71; 95% CI, 0.66-0.76) models had better discrimination than Pa o2 /F io2 (0.64; 95% CI, 0.59-0.69). Both models underestimated risk in lower risk deciles, but exhibited better calibration at relevant risk thresholds. Evaluating practical utility, both LASSO and LASSO + IL-6 models exhibited greater net benefit in decision curve analysis, and greater sample size savings in enrichment analysis, compared with Pa o2 /F io2 . The added utility of LASSO + IL-6 model over LASSO was modest.
Conclusions: Parsimonious, interpretable models that predict persistent HRF may improve enrichment of trials testing HRF-targeted therapies and warrant future validation.
Competing Interests: Drs. Sathe, Morrell, Bhatraju, and Ware received support for article research from the National Institutes of Health (NIH). Dr. Kerchberger’s institution received funding from the National Heart, Lung, and Blood Institute and the American Thoracic Society. Dr. Hough’s institution received funding from the NIH, the American Lung Association, and the Centers for Disease Control and Prevention. Dr. Ware’s institution received funding from the NIH; she received funding from Arrowhead, Akebia, Santhera, Global Blood Therapeutics, and Boehringer Ingelheim; she received support for article research from Genentech and Boehringer Ingelheim; and she disclosed they are a stockholder of Virtuoso Surgical. The remaining authors have disclosed that they do not have any potential conflicts of interest.
(Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)
Design: Prospective cohorts for derivation ( n = 630) and external validation ( n = 511).
Setting: Medical and surgical ICUs at two U.S. medical centers.
Patients: Adults with acute HRF defined as new invasive mechanical ventilation (IMV) and hypoxemia on the first calendar day after ICU admission.
Interventions: None.
Measurements and Main Results: We evaluated discrimination, calibration, and practical utility of models predicting persistent HRF risk (defined as ongoing IMV and hypoxemia on the third calendar day after admission): 1) a clinical model with least absolute shrinkage and selection operator (LASSO) selecting Pa o2 /F io2 , vasopressors, mean arterial pressure, bicarbonate, and acute respiratory distress syndrome as predictors; 2) a model adding interleukin-6 (IL-6) to clinical predictors; and 3) a comparator model with Pa o2 /F io2 alone, representing an existing strategy for enrichment. Forty-nine percent and 69% of patients had persistent HRF in derivation and validation sets, respectively. In validation, both LASSO (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.64-0.73) and LASSO + IL-6 (0.71; 95% CI, 0.66-0.76) models had better discrimination than Pa o2 /F io2 (0.64; 95% CI, 0.59-0.69). Both models underestimated risk in lower risk deciles, but exhibited better calibration at relevant risk thresholds. Evaluating practical utility, both LASSO and LASSO + IL-6 models exhibited greater net benefit in decision curve analysis, and greater sample size savings in enrichment analysis, compared with Pa o2 /F io2 . The added utility of LASSO + IL-6 model over LASSO was modest.
Conclusions: Parsimonious, interpretable models that predict persistent HRF may improve enrichment of trials testing HRF-targeted therapies and warrant future validation.
Competing Interests: Drs. Sathe, Morrell, Bhatraju, and Ware received support for article research from the National Institutes of Health (NIH). Dr. Kerchberger’s institution received funding from the National Heart, Lung, and Blood Institute and the American Thoracic Society. Dr. Hough’s institution received funding from the NIH, the American Lung Association, and the Centers for Disease Control and Prevention. Dr. Ware’s institution received funding from the NIH; she received funding from Arrowhead, Akebia, Santhera, Global Blood Therapeutics, and Boehringer Ingelheim; she received support for article research from Genentech and Boehringer Ingelheim; and she disclosed they are a stockholder of Virtuoso Surgical. The remaining authors have disclosed that they do not have any potential conflicts of interest.
(Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)