During training, models can exploit spurious correlations as shortcuts, resulting in poor generalization performance when shortcuts do not persist. In this work, assuming access to a representation based on domain knowledge (i.e., known concepts) that is invariant to shortcuts, we aim to learn robust and accurate models from biased training data. In contrast to previous work, we do not rely solely on known concepts, but allow the model to also learn unknown concepts. We propose two approaches for mitigating shortcuts that incorporate domain knowledge, while accounting for potentially important yet unknown concepts. The first approach is two-staged. After fitting a model using known concepts, it accounts for the residual using unknown concepts. While flexible, we show that this approach is vulnerable when shortcuts are correlated with the unknown concepts. This limitation is addressed by our second approach that extends a recently proposed regularization penalty. Applied to two real-world datasets, we demonstrate that both approaches can successfully mitigate shortcut learning.

OBJECTIVE: When patients develop acute respiratory failure (ARF), accurately identifying the underlying etiology is essential for determining the best treatment. However, differentiating between common medical diagnoses can be challenging in clinical practice. Machine learning models could improve medical diagnosis by aiding in the diagnostic evaluation of these patients. MATERIALS AND METHODS: Machine learning models were trained to predict the common causes of ARF (pneumonia, heart failure, and/or chronic obstructive pulmonary disease [COPD]). Models were trained using chest radiographs and clinical data from the electronic health record (EHR) and applied to an internal and external cohort. RESULTS: The internal cohort of 1618 patients included 508 (31%) with pneumonia, 363 (22%) with heart failure, and 137 (8%) with COPD based on physician chart review. A model combining chest radiographs and EHR data outperformed models based on each modality alone. Models had similar or better performance compared to a randomly selected physician reviewer. For pneumonia, the combined model area under the receiver operating characteristic curve (AUROC) was 0.79 (0.77-0.79), image model AUROC was 0.74 (0.72-0.75), and EHR model AUROC was 0.74 (0.70-0.76). For heart failure, combined: 0.83 (0.77-0.84), image: 0.80 (0.71-0.81), and EHR: 0.79 (0.75-0.82). For COPD, combined: AUROC = 0.88 (0.83-0.91), image: 0.83 (0.77-0.89), and EHR: 0.80 (0.76-0.84). In the external cohort, performance was consistent for heart failure and increased for COPD, but declined slightly for pneumonia. CONCLUSIONS: Machine learning models combining chest radiographs and EHR data can accurately differentiate between common causes of ARF. Further work is needed to determine how these models could act as a diagnostic aid to clinicians in clinical settings.