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Risk factor identification for incident heart failure using neural network distillation and variable selection

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 Added by Yikuan Li
 Publication date 2021
and research's language is English




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Recent evidence shows that deep learning models trained on electronic health records from millions of patients can deliver substantially more accurate predictions of risk compared to their statistical counterparts. While this provides an important opportunity for improving clinical decision-making, the lack of interpretability is a major barrier to the incorporation of these black-box models in routine care, limiting their trustworthiness and preventing further hypothesis-testing investigations. In this study, we propose two methods, namely, model distillation and variable selection, to untangle hidden patterns learned by an established deep learning model (BEHRT) for risk association identification. Due to the clinical importance and diversity of heart failure as a phenotype, it was used to showcase the merits of the proposed methods. A cohort with 788,880 (8.3% incident heart failure) patients was considered for the study. Model distillation identified 598 and 379 diseases that were associated and dissociated with heart failure at the population level, respectively. While the associations were broadly consistent with prior knowledge, our method also highlighted several less appreciated links that are worth further investigation. In addition to these important population-level insights, we developed an approach to individual-level interpretation to take account of varying manifestation of heart failure in clinical practice. This was achieved through variable selection by detecting a minimal set of encounters that can maximally preserve the accuracy of prediction for individuals. Our proposed work provides a discovery-enabling tool to identify risk factors in both population and individual levels from a data-driven perspective. This helps to generate new hypotheses and guides further investigations on causal links.

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Predicting the incidence of complex chronic conditions such as heart failure is challenging. Deep learning models applied to rich electronic health records may improve prediction but remain unexplainable hampering their wider use in medical practice. We developed a novel Transformer deep-learning model for more accurate and yet explainable prediction of incident heart failure involving 100,071 patients from longitudinal linked electronic health records across the UK. On internal 5-fold cross validation and held-out external validation, our model achieved 0.93 and 0.93 area under the receiver operator curve and 0.69 and 0.70 area under the precision-recall curve, respectively and outperformed existing deep learning models. Predictor groups included all community and hospital diagnoses and medications contextualised within the age and calendar year for each patients clinical encounter. The importance of contextualised medical information was revealed in a number of sensitivity analyses, and our perturbation method provided a way of identifying factors contributing to risk. Many of the identified risk factors were consistent with existing knowledge from clinical and epidemiological research but several new associations were revealed which had not been considered in expert-driven risk prediction models.
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