Explainable time-to-progression predictions in multiple sclerosis.

Journal: Computer methods and programs in biomedicine

Volume: 263

Issue: 

Year of Publication: 

Affiliated Institutions:  KU Leuven, Dept. Public Health and Primary Care, Kortrijk, Belgium; itec, imec research group at KU Leuven, Kortrijk, Belgium. Electronic address: robbe.dhondt@kuleuven.be. KU Leuven, Dept. Public Health and Primary Care, Kortrijk, Belgium; itec, imec research group at KU Leuven, Kortrijk, Belgium. University MS Centre (UMSC), Hasselt University, Hasselt-Pelt, Belgium; Department of Immunology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium; Noorderhart Hospitals, Rehabilitation and MS Centre, Pelt, Belgium; UHasselt, Rehabilitation Research Center (REVAL), Faculty of Rehabilitation Sciences, Diepenbeek, Belgium. Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; CORe, Department of Medicine, University of Melbourne, Melbourne, Australia. Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. Department of Neurology, Jacobs MS center for treatment and research, United States. Department of Neurology, LR SP, Clinical Investigation Centre Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia. Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. Perron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia; Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Australia. Izmir University of Economics, Medical Point Hospital, Izmir, Turkey; Multiple Sclerosis Research Association, Izmir, Turkey. Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy; Multiple Sclerosis Unit, AOU Policlinico "G Rodolico-San Marco", University of Catania, Italy. CHUM MS Center and Universite de Montreal, Montreal, Canada. Institute for Advanced Biomedical Technologies (ITAB), Dept Neurosciences, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy; MS Centre, Clinical Neurology, SS Annunziata University Hospital, Chieti, Italy. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait. Academic MS Center Zuyd, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, Netherlands; School for Mental Health and Neuroscience, Department of Neurology, Maastricht University Medical Center, Maastricht BK, Netherlands. Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Centre, Beirut, Lebanon. Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Université Catholique de Louvain, Belgium. Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal; FP-IID, Instituto de Investigação, Inovação e Desenvolvimento Fernando Pessoa, Portugal; FCS-UFP, Faculdade de Ciências da Saúde, Portugal; RISE-UFP, rede de Investigação em Saúde, Universidade Fernando Pessoa, Porto, Portugal. CSSS Saint-Jérôme, Saint-Jerome, Canada. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy. Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, Australia; University of Queensland, Australia. Department of Neurology, Galliera Hospital, Genova, Italy; Department of Rehabilitation, ML Novarese Hospital Moncrivello, Moncrivello, Italy. Department of Neurology, The Alfred Hospital, Melbourne, Australia; Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Australia. Department of Neurology, Universitary Hospital Ghent, Ghent, Belgium. Department of Neurology, Galdakao-Usansolo University Hospital, Osakidetza-Basque Health Service, Galdakao, Spain; Biocruces-Bizkaia Health Research Institute, Spain. Groene Hart Ziekenhuis, Gouda, Netherlands. Sultan Qaboos University, Al-Khodh, Oman; College of Medicine & Health Sciences and Sultan Qaboos University Hospital, Oman. Neurology department, Hospital Fernandez, Capital Federal, Argentina. Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. Neurology Department, King Fahad Specialist Hospital-Dammam, Saudi Arabia. Perron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia; Sir Charles Gairdner Hospital, Perth, Australia. Jahn Ferenc Teaching Hospital, Budapest, Hungary. Bombay Hospital Institute of Medical Sciences, Mumbai, India. Translational Neuroimmunology Group, Kids Neuroscience Centre and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia; Department of Neurology, Concord Clinical School, Concord Hospital, Sydney, Australia. University MS Centre (UMSC), Hasselt University, Hasselt-Pelt, Belgium; Department of Immunology, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium; I-Biostat, Data Science Institute (DSI), Hasselt University, Diepenbeek, Belgium.

Abstract summary 

Prognostic machine learning research in multiple sclerosis has been mainly focusing on black-box models predicting whether a patients' disability will progress in a fixed number of years. However, as this is a binary yes/no question, it cannot take individual disease severity into account. Therefore, in this work we propose to model the time to disease progression instead. Additionally, we use explainable machine learning techniques to make the model outputs more interpretable.A preprocessed subset of 29,201 patients of the international data registry MSBase was used. Disability was assessed in terms of the Expanded Disability Status Scale (EDSS). We predict the time to significant and confirmed disability progression using random survival forests, a machine learning model for survival analysis. Performance is evaluated on a time-dependent area under the receiver operating characteristic and the precision-recall curves. Importantly, predictions are then explained using SHAP and Bellatrex, two explainability toolboxes, and lead to both global (population-wide) as well as local (patient visit-specific) insights.On the task of predicting progression in 2 years, the random survival forest achieves state-of-the-art performance, comparable to previous work employing a random forest. However, here the random survival forest has the added advantage of being able to predict progression over a longer time horizon, with AUROC >60% for the first 10 years after baseline. Explainability techniques further validated the model by extracting clinically valid insights from the predictions made by the model. For example, a clear decline in the per-visit probability of progression is observed in more recent years since 2012, likely reflecting globally increasing use of more effective MS therapies.The binary classification models found in the literature can be extended to a time-to-event setting without loss of performance, thus allowing a more comprehensive prediction of patient prognosis. Furthermore, explainability techniques proved to be key to reach a better understanding of the model and increase validation of its behaviour.

Authors & Co-authors:  D'hondt Robbe R Dedja Klest K Aerts Sofie S Van Wijmeersch Bart B Kalincik Tomas T Reddel Stephen S Havrdova Eva Kubala EK Lugaresi Alessandra A Weinstock-Guttman Bianca B Mrabet Saloua S Lalive Patrice P Kermode Allan G AG Ozakbas Serkan S Patti Francesco F Prat Alexandre A Tomassini Valentina V Roos Izanne I Alroughani Raed R Gerlach Oliver O Khoury Samia J SJ van Pesch Vincent V Sá Maria José MJ Prevost Julie J Spitaleri Daniele D McCombe Pamela P Solaro Claudio C van der Walt Anneke A Butzkueven Helmut H Laureys Guy G Sánchez-Menoyo José Luis JL de Gans Koen K Al-Asmi Abdullah A Deri Norma N Csepany Tunde T Al-Harbi Talal T Carroll William M WM Rozsa Csilla C Singhal Bhim B Hardy Todd A TA Ramanathan Sudarshini S Peeters Liesbet L Vens Celine C

Study Outcome 

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Citations : 
Authors :  43
Identifiers
Doi : 10.1016/j.cmpb.2025.108624
SSN : 1872-7565
Study Population
Male,Female
Mesh Terms
Other Terms
Disability progression;Explainable artificial intelligence;Longitudinal data;Multiple sclerosis;Survival analysis
Study Design
Study Approach
Country of Study
Publication Country
Ireland