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Machine learning for predicting diverse stroke outcomes: binary, multi-class, and time-to-event
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.ORCID iD: 0009-0006-1030-4237
2026 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Maskininlärning för prediktion av olika utfall efter stroke : binära, ordinala och tid-till-händelse (Swedish)
Abstract [en]

This thesis aimed to improve the clinical prediction of short- and long-term outcomes after stroke by developing, evaluating, and comparing classical statistical and modern machine learning models. Using large, high-quality national stroke registries, specifically the Swedish national stroke register (Riksstroke) and the Sentinel Stroke National Audit Programme (SSNAP), the thesis investigates whether advanced machine learning models offer added value in predicting clinical outcomes compared to traditional models and importantly in which contexts such improvements occur and are clinically meaningful. It addresses several key gaps in the literature, including the lack of external validation for many prediction models across different health systems, the limited research on predicting multi-class functional outcomes, few comprehensive simulation-based evaluations of prediction models under different realistic data conditions, and the need for multiple-horizon evaluations of competing risk prediction models to support fair model selection.

The first paper of the thesis evaluated models for predicting shortterm mortality after stroke using large national registries from two European countries (Riksstroke and SSNAP). The results showed that machine learning models offered only modest performance gains over well-specified logistic regression models, demonstrating that traditional approaches remain competitive, especially when predictors are limited and the dataset is structured.

The second paper performed multi-class prediction of functional outcomes three months after stroke, a clinically important, yet methodologically challenging outcome. All models demonstrated similar overall accuracy. However, machine learning, particularly neural networks and gradient-boosting models, indicated clearer advantages over multinomial logistic regression in distinguishing the functional dependence category. Using explainability approaches such as SHapley Additive exPlanations, the study demonstrated that complex models can still provide interpretable insights into the contribution of risk factors in predictions.

The third paper comprehensively evaluated the classical Cox proportional hazards model and machine learning models for predicting time-to-event outcomes using both simulation and real-world registry data. The Cox regression model performed better when its assumptions were satisfied or when the violations of the assumptions were minimal, while  tree-based models demonstrated better performance in the presence of non-linearity, misspecification, or large number of noise variables.

The final paper compared multiple modeling frameworks for predicting competing risks at multiple evaluation time points (horizons). The results showed that the performance of the models depended on the dataset and the evaluation time point, and no model consistently performed the best. Tree-based and deep-learning models achieved better discrimination when events were common, while pseudo-observation-based and Fine-Gray models showed better calibration, especially at longer horizons.

In summary, the thesis demonstrated that model choice should be guided not by popularity but by data structure, clinical context, and evaluation using different metrics and at multiple time horizons. Traditional and machine learning models each have strengths and rigorous validation, calibration assessment, and explainability are crucial for trustworthy clinical prediction.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2026. , p. 32
Series
Statistical studies, ISSN 1100-8989 ; 61
Keywords [en]
Predictive modeling, Machine learning, Survival analysis, Stroke
Keywords [sv]
Prediktiv modellering, Maskininlärning, Överlevnadsanalys, Stroke
National Category
Probability Theory and Statistics Cardiology and Cardiovascular Disease
Research subject
Statistics
Identifiers
URN: urn:nbn:se:umu:diva-250171ISBN: 978-91-8070-890-6 (print)ISBN: 978-91-8070-891-3 (electronic)OAI: oai:DiVA.org:umu-250171DiVA, id: diva2:2040896
Public defence
2026-03-20, HUM.D.210 - Hummelhonung, Humanisthuset, 09:30 (English)
Opponent
Supervisors
Available from: 2026-02-27 Created: 2026-02-23 Last updated: 2026-02-24Bibliographically approved
List of papers
1. Developing and externally validating a machine learning risk prediction model for 30-day mortality after stroke using national stroke registers in the UK and Sweden.
Open this publication in new window or tab >>Developing and externally validating a machine learning risk prediction model for 30-day mortality after stroke using national stroke registers in the UK and Sweden.
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2023 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 11, article id e069811Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: We aimed to develop and externally validate a generalisable risk prediction model for 30-day stroke mortality suitable for supporting quality improvement analytics in stroke care using large nationwide stroke registers in the UK and Sweden.

DESIGN: Registry-based cohort study.

SETTING: Stroke registries including the Sentinel Stroke National Audit Programme (SSNAP) in England, Wales and Northern Ireland (2013-2019) and the national Swedish stroke register (Riksstroke 2015-2020).

PARTICIPANTS AND METHODS: Data from SSNAP were used for developing and temporally validating the model, and data from Riksstroke were used for external validation. Models were developed with the variables available in both registries using logistic regression (LR), LR with elastic net and interaction terms and eXtreme Gradient Boosting (XGBoost). Performances were evaluated with discrimination, calibration and decision curves.

OUTCOME MEASURES: The primary outcome was all-cause 30-day in-hospital mortality after stroke.

RESULTS: In total, 488 497 patients who had a stroke with 12.4% 30-day in-hospital mortality were used for developing and temporally validating the model in the UK. A total of 128 360 patients who had a stroke with 10.8% 30-day in-hospital mortality and 13.1% all mortality were used for external validation in Sweden. In the SSNAP temporal validation set, the final XGBoost model achieved the highest area under the receiver operating characteristic curve (AUC) (0.852 (95% CI 0.848 to 0.855)) and was well calibrated. The performances on the external validation in Riksstroke were as good and achieved AUC at 0.861 (95% CI 0.858 to 0.865) for in-hospital mortality. For Riksstroke, the models slightly overestimated the risk for in-hospital mortality, while they were better calibrated at the risk for all mortality.

CONCLUSION: The risk prediction model was accurate and externally validated using high quality registry data. This is potentially suitable to be deployed as part of quality improvement analytics in stroke care to enable the fair comparison of stroke mortality outcomes across hospitals and health systems across countries.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2023
Keywords
neurology, quality in health care, statistics & research methods, stroke
National Category
Probability Theory and Statistics Cardiology and Cardiovascular Disease Public Health, Global Health and Social Medicine Neurology
Research subject
Statistics; Neurology
Identifiers
urn:nbn:se:umu:diva-216802 (URN)10.1136/bmjopen-2022-069811 (DOI)001107379900057 ()37968001 (PubMedID)2-s2.0-85177074929 (Scopus ID)
Available from: 2023-11-16 Created: 2023-11-16 Last updated: 2026-02-23Bibliographically approved
2. Developing machine learning models to predict multi-class functional outcomes and death three months after stroke in Sweden
Open this publication in new window or tab >>Developing machine learning models to predict multi-class functional outcomes and death three months after stroke in Sweden
2024 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 5, article id e0303287Article in journal (Refereed) Published
Abstract [en]

Globally, stroke is the third-leading cause of mortality and disability combined, and one of the costliest diseases in society. More accurate predictions of stroke outcomes can guide healthcare organizations in allocating appropriate resources to improve care and reduce both the economic and social burden of the disease. We aim to develop and evaluate the performance and explainability of three supervised machine learning models and the traditional multinomial logistic regression (mLR) in predicting functional dependence and death three months after stroke, using routinely-collected data. This prognostic study included adult patients, registered in the Swedish Stroke Registry (Riksstroke) from 2015 to 2020. Riksstroke contains information on stroke care and outcomes among patients treated in hospitals in Sweden. Prognostic factors (features) included demographic characteristics, pre-stroke functional status, cardiovascular risk factors, medications, acute care, stroke type, and severity. The outcome was measured using the modified Rankin Scale at three months after stroke (a scale of 0-2 indicates independent, 3-5 dependent, and 6 dead). Outcome prediction models included support vector machines, artificial neural networks (ANN), eXtreme Gradient Boosting (XGBoost), and mLR. The models were trained and evaluated on 75% and 25% of the dataset, respectively. Model predictions were explained using SHAP values. The study included 102,135 patients (85.8% ischemic stroke, 53.3% male, mean age 75.8 years, and median NIHSS of 3). All models demonstrated similar overall accuracy (69%-70%). The ANN and XGBoost models performed significantly better than the mLR in classifying dependence with F1-scores of 0.603 (95% CI; 0.594-0.611) and 0.577 (95% CI; 0.568-0.586), versus 0.544 (95% CI; 0.545-0.563) for the mLR model. The factors that contributed most to the predictions were expectedly similar in the models, based on clinical knowledge. Our ANN and XGBoost models showed a modest improvement in prediction performance and explainability compared to mLR using routinely-collected data. Their improved ability to predict functional dependence may be of particular importance for the planning and organization of acute stroke care and rehabilitation.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2024
National Category
Probability Theory and Statistics Cardiology and Cardiovascular Disease
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-224459 (URN)10.1371/journal.pone.0303287 (DOI)001245059300043 ()38739586 (PubMedID)2-s2.0-85192913786 (Scopus ID)
Available from: 2024-05-17 Created: 2024-05-17 Last updated: 2026-02-23Bibliographically approved
3. A comprehesive simulation study evaluating the predictive performance of Cox proportional hazards model and machine learning methods for time-to-event data
Open this publication in new window or tab >>A comprehesive simulation study evaluating the predictive performance of Cox proportional hazards model and machine learning methods for time-to-event data
(English)Manuscript (preprint) (Other academic)
Keywords
Simulation, Machine learning, Survival analysis, Predictive modeling, Stroke.
National Category
Probability Theory and Statistics Cardiology and Cardiovascular Disease
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-250167 (URN)
Funder
Swedish Research Council, 2024-02846Swedish Research Council, 2022-02046
Available from: 2026-02-23 Created: 2026-02-23 Last updated: 2026-02-24Bibliographically approved
4. Predictive performance at different time horizons in the presence of competing risks: machine learning versus statistical time-to-event models
Open this publication in new window or tab >>Predictive performance at different time horizons in the presence of competing risks: machine learning versus statistical time-to-event models
(English)Manuscript (preprint) (Other academic)
Keywords
Competing risk, machine learning, pseudo-observations, stroke
National Category
Cardiology and Cardiovascular Disease Probability Theory and Statistics
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-250169 (URN)
Funder
Swedish Research Council, 2024-02846
Available from: 2026-02-23 Created: 2026-02-23 Last updated: 2026-02-24Bibliographically approved

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