| Creators: |
Buchka, Stefan and Hapfelmeier, Alexander and Kirschke, Jan S. and Steuerwald, Verena and Naumann, Markus and Soto-Rey, Inaki and Rohr, Sven O. and Kramer, Frank and Behrens, Lars and Oswald, Eva and Kümpfel, Tania and Zimmermann, Hanna and Hoffmann, Verena S. and Hagedorn, Marlien and Albashiti, Fady and Krumbholz, Markus and Ziemann, Ulf and Kohlbacher, Oliver and Sailer, Benjamin and Braunmüller, Viola and Biergans, Stephanie and de Arrudo Botelho Herr, Marius and Ernemann, Ulrike and Bürkle, Eva and Bender, Benjamin and Daul, Andreas and Ruff, Christer and Römhild, Jörg and Wiestler, Benedikt and Sepp, Dominik and Spengler, Helmut and Pallaoro, Peter and Boeker, Martin and Kohlmayer, Florian and Dehmelt, Vera and Berthele, Achim and Mühlau, Mark and Uibel, Paula and Wauschkuhn, Josephine and Kuhn, Klaus and Senel, Makbule and Vardakas, Ioannis and Taranu, Daniela and Kestler, Hans A. and Sollmann, Nico and Irmak Ön, Begüm and Bilger, Sandra and Mansmann, Ulrich and Bayas, Antonios and Havla, Joachim and Kowarik, Markus C. and Tumani, Hayrettin and Hemmer, Bernhard and ProVal-MS-Study Group |
| Abstract (ENG): |
Background:
The course of relapsing-remitting multiple sclerosis (RRMS), frequently preceded by the clinically isolated syndrome (CIS), is variable and challenging to predict. Given many treatment options available, prognostic algorithms are gaining importance in informing initial treatment decisions. However, to date, only a few externally validated exists. External validation, which involves the application of a model to independent data, is essential. Privacy-preserving federated analyses of individual-level data facilitate external validation using clinical datasets that are typically difficult to access.
Objectives:
Using data from the ProVal-MS study to externally validate the multiple sclerosis treatment decision score (MS-TDS), a predictive algorithm for early RRMS and CIS. The MS-TDS predicts the probability of the occurrence of at least one new or enlarging T2 lesion within 6–24 months following the onset of the disease and supports choosing between initiating platform treatment or a ‘wait-and-see’ approach. A secondary objective is to demonstrate the feasibility of privacy-preserving federated concepts within the Data Integration for Future Medicine (DIFUTURE) consortium.
Design:
Prospective, multicentric, non-interventional cohort study (ProVal-MS) within DIFUTURE.
Methods:
The calibrated MS-TDS was evaluated using the area under the receiver operating characteristic curve (AUROC) and the Brier score in both pooled and distributed settings. A decision curve analysis (DCA) was used to evaluate the net benefit of treatment decisions made by the MS-TDS in comparison to those made by treating neurologists.
Results:
Of the 271 individuals diagnosed with CIS or early RRMS, 202 (78.2%) received platform treatment, while 59 (21.8%) did not receive treatment. The AUROC was 0.561 (95% CI: 0.492–0.630) in the pooled analysis and 0.567 (95% CI: 0.496–0.634) in the distributed analysis. DCA demonstrated a net benefit that was commensurate with that achieved by decisions made by experienced neurologists.
Conclusion:
The external validation of the MS-TDS demonstrated low, non-significant predictive performance; however, it may serve as a useful complement, particularly for less-experienced neurologists. The distributed validation was found to be both feasible and compliant with data protection regulations. |
| Citation: |
Buchka, Stefan and Hapfelmeier, Alexander and Kirschke, Jan S. and Steuerwald, Verena and Naumann, Markus and Soto-Rey, Inaki and Rohr, Sven O. and Kramer, Frank and Behrens, Lars and Oswald, Eva and Kümpfel, Tania and Zimmermann, Hanna and Hoffmann, Verena S. and Hagedorn, Marlien and Albashiti, Fady and Krumbholz, Markus and Ziemann, Ulf and Kohlbacher, Oliver and Sailer, Benjamin and Braunmüller, Viola and Biergans, Stephanie and de Arrudo Botelho Herr, Marius and Ernemann, Ulrike and Bürkle, Eva and Bender, Benjamin and Daul, Andreas and Ruff, Christer and Römhild, Jörg and Wiestler, Benedikt and Sepp, Dominik and Spengler, Helmut and Pallaoro, Peter and Boeker, Martin and Kohlmayer, Florian and Dehmelt, Vera and Berthele, Achim and Mühlau, Mark and Uibel, Paula and Wauschkuhn, Josephine and Kuhn, Klaus and Senel, Makbule and Vardakas, Ioannis and Taranu, Daniela and Kestler, Hans A. and Sollmann, Nico and Irmak Ön, Begüm and Bilger, Sandra and Mansmann, Ulrich and Bayas, Antonios and Havla, Joachim and Kowarik, Markus C. and Tumani, Hayrettin and Hemmer, Bernhard and ProVal-MS-Study Group
(2025)
External validation of a multiple sclerosis treatment decision score using data from the ProVal-MS cohort study.
Therapeutic Advances in Neurological Disorders, 18, Paper / Research Article.
ISSN 1756-2864
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