A community-validated tool for clinical outcome calculation in multiple sclerosis: Consensus development and scenario-specific recommendations

Abstract

Background: Reproducibility and comparability of disability outcomes remain major challenges in multiple sclerosis (MS) research. Definitions of disability progression vary widely across studies, and calculation criteria are often insufficiently documented to enable replication. Framework: To address these issues, a consensus process endorsed by the International Advisory Committee on Clinical Trials in MS was conducted to develop practical guidelines for outcome calculation across a range of study designs and research questions. Instead of proposing a single universal endpoint definition, we establish specific recommendations for each use case, within a fixed parameter space derived from extraction and systematisation of common practices for baseline selection, event confirmation, relapse handling, and event categorisation. These criteria are implemented in a shared computational framework, “msprog,” available as open-source R and Python software and as a web application. The tool supports different disability scales, facilitates full reporting of parameters, and adapts to both clinical trial and real-world settings. Conclusion: The integration of consensus-based guidelines with a standardised, extensible implementation provides a practical basis for consistent and reproducible specification of disability outcomes in MS.