A Digital Twin for Individualized Treatment Effects of Non-Invasive Respiratory Support Strategies (DINIRS)
Abstract
Objective: Choosing between noninvasive respiratory support (NIRS) and invasive mechanical ventilation (IMV) for acute respiratory failure is a time-sensitive decision. Although guidelines provide population-level guidance, it remains unclear who benefits more from NIRS than IMV. The standard outcome, ventilator-free days at 28 days (VFD-28), scores death and prolonged ventilation equally, and current estimators do not distinguish between them. We developed and validated a censoring-aware Digital Twin framework for Individualized Treatment Effects of Non-Invasive Respiratory Support (DINIRS) to estimate individualized treatment effects (ITEs) that capture both mortality and ventilation duration. Materials and Methods: We emulated a target trial in 5,336 MIMIC-IV patients and trained DINIRS on 23 baseline clinical variables measured during the first 24 ICU hours. A transformer encoder with a survival attention gate decomposed VFD-28 into survival probability and conditional ventilation duration. A cross-fitted, doubly robust learner estimated ITEs. We externally validated DINIRS in 2,540 patients from the multi-site eICU-CRD dataset without retraining. Results: The DINIRS policy achieved a mean benefit of 2.07 ventilator-free days per patient (207 per 100 patients) compared with observed practice. Predicted NIRS benefit was higher among patients with less organ dysfunction (88.4% versus 49.0%) and persisted across hypoxemia severity. External validation reproduced this pattern. Discussion: The NIRS benefit stemmed from shorter ventilation among survivors rather than from reduced mortality, indicating that avoiding intubation-associated complications was the primary mechanism. Conclusion: Prospective validation is needed before these estimates inform treatment decisions. The decomposition framework can be extended beyond respiratory support to any zero-inflated composite outcome.
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BibTeX
@misc{islam2026digital,
title = {{A Digital Twin for Individualized Treatment Effects of Non-Invasive Respiratory Support Strategies (DINIRS)}},
author = {Md Fantacher Islam and Jarrod Mosier and Vignesh Subbian},
howpublished = {arXiv},
year = {2026},
month = sep,
doi = {10.48550/arxiv.2608.26915},
eprint = {2608.26915},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2608.26915},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - UNPB
TI - A Digital Twin for Individualized Treatment Effects of Non-Invasive Respiratory Support Strategies (DINIRS)
AU - Md Fantacher Islam
AU - Jarrod Mosier
AU - Vignesh Subbian
PY - 2026
DA - 2026/09/19
PB - arXiv
DO - 10.48550/arxiv.2608.26915
UR - https://arxiv.org/abs/2608.26915
AB - Objective: Choosing between noninvasive respiratory support (NIRS) and invasive mechanical ventilation (IMV) for acute respiratory failure is a time-sensitive decision. Although guidelines provide population-level guidance, it remains unclear who benefits more from NIRS than IMV. The standard outcome, ventilator-free days at 28 days (VFD-28), scores death and prolonged ventilation equally, and current estimators do not distinguish between them. We developed and validated a censoring-aware Digital Twin framework for Individualized Treatment Effects of Non-Invasive Respiratory Support (DINIRS) to estimate individualized treatment effects (ITEs) that capture both mortality and ventilation duration. Materials and Methods: We emulated a target trial in 5,336 MIMIC-IV patients and trained DINIRS on 23 baseline clinical variables measured during the first 24 ICU hours. A transformer encoder with a survival attention gate decomposed VFD-28 into survival probability and conditional ventilation duration. A cross-fitted, doubly robust learner estimated ITEs. We externally validated DINIRS in 2,540 patients from the multi-site eICU-CRD dataset without retraining. Results: The DINIRS policy achieved a mean benefit of 2.07 ventilator-free days per patient (207 per 100 patients) compared with observed practice. Predicted NIRS benefit was higher among patients with less organ dysfunction (88.4% versus 49.0%) and persisted across hypoxemia severity. External validation reproduced this pattern. Discussion: The NIRS benefit stemmed from shorter ventilation among survivors rather than from reduced mortality, indicating that avoiding intubation-associated complications was the primary mechanism. Conclusion: Prospective validation is needed before these estimates inform treatment decisions. The decomposition framework can be extended beyond respiratory support to any zero-inflated composite outcome.
ER -