ESTIMATING EFFECT MAGNITUDE TO CONSIDER TREATMENT DISEASE-MODIFYING IN MULTIPLE SYSTEM ATROPHY: STRUCTURED EXPERT ELICITATION IN A RARE DISEASE
Author(s)
Igor Kuchin, MD MSc1, Oluwasemire Kola Olalere, MSc1, Marjan Arvandi, PhD1, Katharina Reber, MSc1, Gaby Sroczynski, MPH, DrPH1, Elisabeth Nöhammer, PhD1, Bianca Calio, MD2, Fabian Leys, MD PhD2, Frank Jagusch, MD2, Maria Schneller, MSc3, Klaus Seppi, MD PhD2, Stefan Kiechl, MD PhD2, Werner Poewe, MD PhD2, Florian Krismer, MD PhD2, Petra Schwingenschuh, MD PhD3, Alessandra Fanciulli, MD PhD2, Uwe Siebert, MPH MSc ScD1, Beate Jahn, PhD1.
1UMIT TIROL – University for Health Sciences and Technology, Hall in Tirol, Austria, 2Medical University Innsbruck, Innsbruck, Austria, 3Medical University of Graz, Graz, Austria.
1UMIT TIROL – University for Health Sciences and Technology, Hall in Tirol, Austria, 2Medical University Innsbruck, Innsbruck, Austria, 3Medical University of Graz, Graz, Austria.
OBJECTIVES: Multiple System Atrophy (MSA) is a rare, rapidly progressive neurodegenerative disease affecting movement and autonomic function, with no available disease-modifying treatments. Clinical trials evaluate treatment effectiveness using the Unified MSA Rating Scale (UMSARS), which captures activities of daily living (UMSARS I), motor function (UMSARS II), and disease stage (UMSARS IV: 1 = completely independent to 5 = totally dependent). However, treatment trial protocols typically assume a 30-40% reduction in disease progression regardless of UMSARS IV stage. This study estimated UMSARS IV stage-specific effect magnitude required to consider treatment disease-modifying in MSA through structured expert elicitation.
METHODS: The elicitation included experts from six regional and international movement disorder societies. UMSARS I, II, and I+II were ranked by importance for assessing treatment effectiveness, then stage-specific estimates of effect magnitude were elicited. For each sub-scale, experts estimated effect magnitude in UMSARS IV stage 1 relative to an external anchor derived from the European MSA cohort. The estimate in UMSARS IV stage 1 served as an expert-specific anchor value when estimating effect waning across successive stages. Effectiveness in misdiagnosed cases was estimated for Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). Mean effect magnitude and 95% confidence intervals (95% CI) are reported.
RESULTS: 84 experts completed the elicitation, including 54 from Europe. 70.9% ranked UMSARS I+II as most important for assessing disease progression. Mean disease-modifying effect magnitude was 55% (95% CI: 51%-59%) in UMSARS IV stage 1, declining by 8-15% per stage to 12% (95% CI: 9%-15%) at stage 5. For misdiagnosed cases, 85% agreed MSA-specific treatment would be less effective or ineffective in PSP; no consensus was reached for PD.
CONCLUSIONS: Expert elicitation defined stage-specific disease-modifying effect magnitude in MSA. An algorithm will be developed to translate expert-defined effect magnitude into patient-relevant outcomes for decision-analytic modeling of care strategies, such as the MeDeMSA Care trial (NCT06072105).
METHODS: The elicitation included experts from six regional and international movement disorder societies. UMSARS I, II, and I+II were ranked by importance for assessing treatment effectiveness, then stage-specific estimates of effect magnitude were elicited. For each sub-scale, experts estimated effect magnitude in UMSARS IV stage 1 relative to an external anchor derived from the European MSA cohort. The estimate in UMSARS IV stage 1 served as an expert-specific anchor value when estimating effect waning across successive stages. Effectiveness in misdiagnosed cases was estimated for Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). Mean effect magnitude and 95% confidence intervals (95% CI) are reported.
RESULTS: 84 experts completed the elicitation, including 54 from Europe. 70.9% ranked UMSARS I+II as most important for assessing disease progression. Mean disease-modifying effect magnitude was 55% (95% CI: 51%-59%) in UMSARS IV stage 1, declining by 8-15% per stage to 12% (95% CI: 9%-15%) at stage 5. For misdiagnosed cases, 85% agreed MSA-specific treatment would be less effective or ineffective in PSP; no consensus was reached for PD.
CONCLUSIONS: Expert elicitation defined stage-specific disease-modifying effect magnitude in MSA. An algorithm will be developed to translate expert-defined effect magnitude into patient-relevant outcomes for decision-analytic modeling of care strategies, such as the MeDeMSA Care trial (NCT06072105).
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA54
Topic
Clinical Outcomes, Methodological & Statistical Research, Study Approaches
Topic Subcategory
Surveys & Expert Panels
Disease
Neurological Disorders, Rare & Orphan Diseases