Dynamic, Interpretable, Machine Learning–Based Outcome Prediction as a New Emerging Opportunity in Acute Ischemic Stroke Patient Care: A Proof‐of‐Concept Study

<b>Introduction:</b> While the machine learning (ML) model's black-box nature presents a significant barrier to effective clinical application, the dynamic nature of stroke patients' recovery further undermines the reliability of established predictive scores and models, making them less suitable for accurate prediction and appropriate patient care. This research is aimed at building and evaluating an interpretable ML-based model, which would perform outcome prediction at different time points of patients' recovery, giving more secure and understandable output through interpretable packages. <b>Materials and Methods:</b> A retrospective analysis was conducted on acute ischemic stroke (AIS) patients treated with alteplase at the Neurology Clinic of the University Clinical Center of Vojvodina (Novi Sad, Serbia), for 14 years. Clinical data were grouped into four categories based on collection time-baseline, 2-h, 24-h, and discharge features-serving as inputs for three different classifiers-support vector machine (SVM), logistic regression (LR), and random forest (RF). The 90-day modified Rankin scale (mRS) was used as the outcome measure, distinguishing between favorable (mRS ≤ 2) and unfavorable outcomes (mRS ≥ 3). <b>Results:</b> The sample was described with 49 features and included 355 patients, with a median age of 67 years (interquartile range (IQR) 60-74 years), 66% being male. The models achieved strong discrimination in the testing set, with area under the curve (AUC) values ranging from 0.80 to 0.96. Additionally, they were compared with a model based on the DRAGON score, which showed an AUC of 0.760 (95% confidence interval (CI), 0.640-0.862). The decision-making process was more thoroughly understood using interpretable packages: Shapley additive explanation (SHAP) and local interpretable model-agnostic explanation (LIME). They revealed the most significant features at both the group and individual patient levels. <b>Conclusions and Clinical Implications:</b> This study demonstrated the moderate to strong efficacy of interpretable ML-based models in predicting the functional outcomes of alteplase-treated AIS patients. In all constructed models, age, onset-to-treatment time, and platelet count were recognized as the important predictors, followed by clinical parameters measured at different time points, such as the National Institutes of Health Stroke Scale (NIHSS) and systolic and diastolic blood pressure values. The dynamic approach, coupled with interpretable models, can aid in providing insights into the potential factors that could be modified and thus contribute to a better outcome.