External validation of a biomarker and clinical prediction model for hospital mortality in acute respiratory distress syndrome
Mortality prediction in ARDS is important for prognostication and risk stratification. However, no prediction models have been independently validated. A combination of two biomarkers with age and APACHE III was superior in predicting mortality in the NHLBI ARDSNet ALVEOLI trial. We validated this prediction tool in two clinical trials and an observational cohort.
The validation cohorts included 849 patients from the NHLBI ARDSNet Fluid and Catheter Treatment Trial (FACTT), 144 patients from a clinical trial of sivelestat for ARDS (STRIVE), and 545 ARDS patients from the VALID observational cohort study. To evaluate the performance of the prediction model, the area under the receiver operating characteristic curve (AUC), model discrimination, and calibration were assessed, and recalibration methods were applied.
The biomarker/clinical prediction model performed well in all cohorts. Performance was better in the clinical trials with an AUC of 0.74 (95% CI 0.70–0.79) in FACTT, compared to 0.72 (95% CI 0.67–0.77) in VALID, a more heterogeneous observational cohort. The AUC was 0.73 (95% CI 0.70–0.76) when FACTT and VALID were combined.
We validated a mortality prediction model for ARDS that includes age, APACHE III, surfactant protein D, and interleukin-8 in a variety of clinical settings. Although the model performance as measured by AUC was lower than in the original model derivation cohort, the biomarker/clinical model still performed well and may be useful for risk assessment for clinical trial enrollment, an issue of increasing importance as ARDS mortality declines, and better methods are needed for selection of the most severely ill patients for inclusion.
KeywordsValidation Prediction Biomarker Hospital mortality ARDS
American European Consensus Conference
Acute lung injury
Acute physiology and chronic health evaluation
Acute respiratory distress syndrome
Area under receiver operating characteristic curve
Fluid and catheter treatment trial
Intensive care unit
Integrated discrimination improvement
National Heart, Lung, and Blood Institute
Net reclassification improvement
Positive end-expiratory pressure
Receiver operating characteristic curve
Sivelestat trial in ALI patients requiring mechanical ventilation
Validating acute lung injury biomarkers for diagnosis
This manuscript was prepared using FACTT Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center and does not necessarily reflect the opinions or views of the FACTT investigators or the NHLBI. We would like to thank the NHLBI BioLINCC/Biorepository for providing clinical samples and clinical data from the FACTT clinical trial. We also thank Eli Lilly and Company for providing clinical data and plasma samples from the STRIVE study.
Compliance with ethical standards
This study was supported by NIH HL112656 (LBW), 1K23HL116800-01 (KK), HL51856 (MAM), HL110969 and HL131621 (CSC), and the NHLBI BioLINCC/Biorepository.
Conflicts of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study with the exception of some patients in the VALID study who were enrolled under an IRB-approved waiver of informed consent.
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