From Continuous Predictors to Clinical Thresholds: Early Evidence on Performance Trade-offs of Guideline-Based Categorisation for Ischaemic Stroke Outcome Prediction
Authors: Esra Zihni, Katryna Cisek, Hamzah Ziadeh, Hendrik Knoche, Robert Mikulik, John D. Kelleher
Organizations: Artificial Intelligence in Digital Health and Medicine, Technological University Dublin, Ireland · Aalborg University, Aalborg, Denmark · International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia · Health Management Institute, Brno, Czechia · Trinity College Dublin, Ireland
Machine learning models achieve strong predictive accuracy for 90-day outcome prediction in acute ischaemic stroke, yet clinical adoption is limited by the misalignment of model explanations with clinicians' reasoning. Motivated by a clinician user study calling for clinical guideline-aligned cut-offs, we ask whether continuous predictors can be replaced by clinically informed categorical encodings without sacrificing performance. On a multi-centre European registry stratified into three treatment cohorts, we compare standard and fully categorised gradient-boosted models, the latter using stroke guideline-aligned, treatment-specific thresholds. The fully categorised models are statistically indistinguishable from their continuous counterparts in two of the treatment cohorts, with a significant drop in predictive accuracy in one cohort. Global feature importance rankings remain consistent, suggesting that discretising continuous predictors into guideline-based categories preserves the core hierarchy of prognostic factors across all treatment groups. Guideline-based categorisation is thus a viable design choice for stroke-outcome models.
Every year in the United States, 800,000 individuals suffer a stroke - one person every 40 seconds, with a death occurring every four minutes. While individual factors vary, certain predictors are more prevalent in determining stroke risk. As strokes are the second leading cause of death and disability worldwide, predicting stroke likelihood based on lifestyle factors is crucial. Showing individuals their stroke risk could motivate lifestyle changes, and machine learning offers solutions to this prediction challenge. Neural networks excel at predicting outcomes based on training features like lifestyle factors, however, they're not the only option. Logistic regression models can also effectively compute the likelihood of binary outcomes based on independent variables, making them well-suited for stroke prediction. This analysis will compare both neural networks (dense and convolutional) and logistic regression models for stroke prediction, examining their pros, cons, and differences to develop the most effective predictor that minimizes false negatives.
Multimodal prediction models based on imaging and clinical data are increasingly used for clinical decision support, yet their interpretability remains limited. We present multimodal Deep Transformation Models (DTMs) combining statistical approaches and neural networks to achieve strong predictive performance while preserving interpretability for tabular data. A key contribution of this work is the adaption of the xAI methods Grad-CAM and Occlusion to DTMs relying on 3D CNNs, enabling interpretation of the image branch through the generation of explanation maps. We developed DTMs to predict functional independence three months after stroke using diffusion-weighted imaging and clinical data from 407 patients. In a ten-fold cross-validation, the models achieved state-of-the-art predictive performance (AUC 0.81 [0.75, 0.87]) while maintaining interpretability for tabular features, with functional independence before stroke and stroke severity on admission emerging as the strongest predictors. Explanation maps from both xAI methods highlighted consistent regions, including frontal lobe areas which are known to be associated with age, a strong predictor of functional outcome. Notably, these regions disappeared once age was included as an explicit tabular predictor. Similarity analyses of explanation maps revealed distinct spatial patterns, providing meaningful insights into stroke pathophysiology, systematic error analysis and hypothesis generation.
Lisa Herzog, Jonas Brändli, Maurice Schneeberger +7
Personalized medicine in acute ischemic stroke requires moving beyond average treatment effects (ATE) to individualized treatment effect (ITE) estimates to support treatment decisions. In acute ischemic stroke, mechanical thrombectomy has been shown to be more effective on average than lysis in randomized controlled trials (RCTs), such as the MR CLEAN study. We aim to identify which individual patients benefit most from mechanical thrombectomy compared to lysis. The outcome of interest is the modified Rankin Scale (mRS) at three months, an ordinal measure of functional disability (0: no symptoms, 6: death). We demonstrate that causal transformation models on directed acyclic graphs (TRAM-DAG) can be used for ITE estimation after being fitted on observational MAGIC multi-center stroke patient data. To ensure comparability with the MR CLEAN population, which we use for validation, we train the TRAM-DAG on a MAGIC sub-population with NIHSS at admission >= 6, corresponding to one inclusion criterion of MR CLEAN. The fitted model is then used to estimate ITEs for stroke patients in the MR CLEAN population. While these ITE estimates cannot be confirmed experimentally, we show that their average is consistent with the trial's reported ATE. Furthermore, the ITE estimates correctly rank trial patients by their observed frequency of a good outcome (mRS at three months <= 2). These findings support the use of causal models like TRAM-DAG for personalized decision-making in stroke care and highlight their ability to bridge the gap between observational evidence and clinical trials.