EQ-5D Analysis in a Rare Disease: Utilities Across Disease Stages in Multiple-System Atrophy
Author(s)
Igor Kuchin, MD MSc1, Sibylle Puntscher, PhD1, Gaby Sroczynski, MPH DrPH1, Marjan Arvandi, MStat PhD1, Julia Santamaria, MA1, Daniela Schmid, PhD2, Georg Goebel, Mag PhD3, Florian Krismer, MD PhD4, Anette Schrag, MD PhD5, Petra Schwingenschuh, MD PhD6, Alessandra Fanciulli, MD PhD4, Uwe Siebert, MPH MSc ScD MD7, Beate Jahn, PhD1.
1Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences and Technology, Hall in Tirol, Austria, 2Faculty of Life Sciences, Albstadt-Sigmaringen University, Sigmaringen, Germany, 3Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University Innsbruck, Innsbruck, Austria, 4Department of Neurology, Medical University Innsbruck, Innsbruck, Austria, 5Department of Clinical and Movement Neurosciences, University College London, London, United Kingdom, 6Department of Neurology, Medical University of Graz, Graz, Austria, 7Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences and Technology; Harvard Chan School of Public Health; Harvard Medical School, Hall in Tirol, Austria.
1Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences and Technology, Hall in Tirol, Austria, 2Faculty of Life Sciences, Albstadt-Sigmaringen University, Sigmaringen, Germany, 3Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University Innsbruck, Innsbruck, Austria, 4Department of Neurology, Medical University Innsbruck, Innsbruck, Austria, 5Department of Clinical and Movement Neurosciences, University College London, London, United Kingdom, 6Department of Neurology, Medical University of Graz, Graz, Austria, 7Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL – University for Health Sciences and Technology; Harvard Chan School of Public Health; Harvard Medical School, Hall in Tirol, Austria.
OBJECTIVES: Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder. In the European MSA Study Group (EMSA) natural history cohort, average health-related quality of life (HRQoL) was lower than in advanced cancers, yet MSA severity stages were not considered. This study aims to derive HRQoL by calculating EQ-5D-3L-based utility values stratified by MSA severity to inform health technology assessment of best medical care proposed in MeDeMSA clinical trial (NCT06072105).
METHODS: We retrospectively analyzed EMSA data. EQ-5D-3L health states were mapped to severity stages defined by the Unified MSA Rating Scale Part IV (UMSARS IV). EQ-5D-3L responses were converted into utility values using the reverse crosswalk method with the German time trade-off value set, enabling comparison with EQ-5D-5L-based findings. Plausibility was assessed using ordinal logit, linear mixed-effects, and generalized additive models. To address extreme values, sensitivity analyses applied symmetric trimming and winsorizing data, retaining the central 99%, 95%, 90%, and 80% of values. Missing data were evaluated, and appropriate imputation applied.
RESULTS: A total of 283 observations from 85 individuals were analyzed. Mean utility values declined from 0.732 (95% confidence interval (CI): 0.587-0.876) in UMSARS IV stage 1 to 0.202 (95% CI: 0.138-0.266) in stage 5. Winsorizing and trimming narrowed confidence intervals but did not substantially affect mean estimates. In linear mixed-effects models with random intercepts for individuals, disease severity explained 36.0% of utility variance, followed by pain (32.7%) and depression (16.9%). Three UMSARS IV entries and eight utility values were flagged as implausible based on model predictions assuming consistent health states and reasonable utility ranges. Of seven missing UMSARS IV values, one was imputed no EQ-5D data were imputed.
CONCLUSIONS: Our study provides the first utility estimates in MSA stratified by disease severity. Next, we will generate robust utility values to support health technology assessment of best medical care in MSA.
METHODS: We retrospectively analyzed EMSA data. EQ-5D-3L health states were mapped to severity stages defined by the Unified MSA Rating Scale Part IV (UMSARS IV). EQ-5D-3L responses were converted into utility values using the reverse crosswalk method with the German time trade-off value set, enabling comparison with EQ-5D-5L-based findings. Plausibility was assessed using ordinal logit, linear mixed-effects, and generalized additive models. To address extreme values, sensitivity analyses applied symmetric trimming and winsorizing data, retaining the central 99%, 95%, 90%, and 80% of values. Missing data were evaluated, and appropriate imputation applied.
RESULTS: A total of 283 observations from 85 individuals were analyzed. Mean utility values declined from 0.732 (95% confidence interval (CI): 0.587-0.876) in UMSARS IV stage 1 to 0.202 (95% CI: 0.138-0.266) in stage 5. Winsorizing and trimming narrowed confidence intervals but did not substantially affect mean estimates. In linear mixed-effects models with random intercepts for individuals, disease severity explained 36.0% of utility variance, followed by pain (32.7%) and depression (16.9%). Three UMSARS IV entries and eight utility values were flagged as implausible based on model predictions assuming consistent health states and reasonable utility ranges. Of seven missing UMSARS IV values, one was imputed no EQ-5D data were imputed.
CONCLUSIONS: Our study provides the first utility estimates in MSA stratified by disease severity. Next, we will generate robust utility values to support health technology assessment of best medical care in MSA.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
P62
Topic
Clinical Outcomes, Methodological & Statistical Research, Patient-Centered Research
Topic Subcategory
Health State Utilities, Patient-reported Outcomes & Quality of Life Outcomes
Disease
Neurological Disorders, No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases