This Workstream continues to provide a comprehensive framework for translating innovation into clinical research and care by developing methodologies and infrastructures that assess clinical meaningfulness and patient benefits.

These efforts focus on generating high-quality real-world evidence, leveraging RC2NB's interdisciplinary expertise, and fostering pragmatic, decentralized, and remote clinical trials. This integration enhances the seamless translation of research findings into routine care.

Flagship Initiative: MultiSCRIPT embedded in the Swiss MS Cohort



MultiSCRIPT (MultipleSclerosis Pragmatic Platform Trial), an investigator-initiated study exemplifying RC2NB’smission of seamlessly integrating research into care. The effectiveness and clinical meaningfulness of innovative treatment strategies are continuously evaluated with pragmatic research methodologies. As a transformative learning care system launchedin 2022 and funded by the Swiss NationalScience Foundation, MultiSCRIPT is embedded within the Swiss MS Cohort (SMSC), led by Prof. Jens Kuhle (s. WS2). SMSC is a long-standing, high-quality cohort study characterized by standardized procedures and robust, high quality real-world data collection. It provides the ideal foundation for mergingpragmatic randomized trial methodology with real-world evidence generation.

MultiSCRIPT’s ultimategoal is to establish personalized treatment approaches, directly embedded into routine care for persons with multiple sclerosis (MS).

Led by Prof. Oezguer Yaldizli (co-PIs Prof. Jens Kuhle, Prof. Lars Hemkens, and Prof. Chiara Zecca from Lugano, scientific coordination by Dr. Perrine Janiaud), MultiSCRIPT’s first cycle evaluates a biomarker monitoring strategy using serum neurofilament light chain (sNfL) values for personalized treatment decisions compared to standard care in a randomized trial design. This approach aims to improve either the proportion of patients achieving no evidence of disease activity (NEDA3) or their health-related quality of life. If proven superior, the strategy will establish a new standard of care, paving the way for future cycles to evaluate other innovative diagnostic or treatment approaches. After its full integration into the SMSC, that enabled streamlined patient randomization using digital tools for data collection, and optimized consentand quality- of-life measurement processes, MultiSCRIPT rapidly recruited nearly 2/3 of the target sample size in less than a year (Figure 9) with additional SMSC centers coming on board.