Multiple System Atrophy Combined Outcome Assessment (MuSyCA): process, format, and validation plan

Area of Science:

• Neuroscience
• Clinical Trials
• Biomarkers

Background:

• The Unified Multiple System Atrophy Rating Scale (UMSARS) has limitations for clinical trial use in Multiple System Atrophy (MSA).
• There is a need for comprehensive outcome measures to assess disease modification in MSA clinical trials.

Purpose of the Study:

• To describe the development and validation plan for the Multiple System Atrophy Combined Outcome Assessment (MuSyCA).
• To outline MuSyCA's structure, intended use, and assessment of its reliability, validity, and sensitivity in tracking MSA progression.

Main Methods:

• Candidate outcome assessments identified via systematic literature review and longitudinal MSA cohort data analysis.
• Content refined through Delphi-like consensus rounds with experts, patient advocates, and industry stakeholders.
• Cognitive interviews with 20 MSA patients evaluated patient- and clinician-reported outcomes; validation includes construct validity, internal consistency, test-retest reliability, and responsiveness.

Main Results:

• MuSyCA integrates patient- and clinician-reported outcomes, biomarkers (neurofilament light chain, neuroimaging), and performance-based measures.
• This multimodal approach captures subjective and objective aspects of MSA progression, improving detection of treatment effects.
• MuSyCA is specifically designed for clinical trials and not for clinical practice.

Conclusions:

• MuSyCA provides a multidimensional approach for precise, disease-relevant evaluations in trials for disease-modifying therapies in MSA.
• Ongoing validation will establish MuSyCA as a standardized multimodal outcome measure, crucial for advancing MSA therapeutic development.