AN 8-POINT WORSENING AND A 10-POINT IMPROVEMENT ON THE MULTIPLE-SCLEROSIS IMPACT SCALE 29-ITEM (MSIS-29) V2 ARE CLINICALLY MEANINGFUL
Author(s)
Ying-Fang Chen, PhD1, Tammy McIver, MSc2, Tracy Holt, MPH, MS3, jeremy C. hobart, PhD4.
1Genentech, Inc., South San Francisco, CA, USA, 2Roche Products Ltd, Welwyn Garden City, United Kingdom, 3PAREXEL International, Billerica, MA, USA, 4Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom.
1Genentech, Inc., South San Francisco, CA, USA, 2Roche Products Ltd, Welwyn Garden City, United Kingdom, 3PAREXEL International, Billerica, MA, USA, 4Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom.
OBJECTIVES: To determine meaningful within-patient change (MWPC) thresholds for clinical worsening and improvement on the MSIS-29v2 physical and psychological impact scales in people with primary progressive and relapsing multiple sclerosis (pwPPMS and pwRMS). This addresses the lack of established thresholds for MSIS-29v2. Currently, the only published benchmark is a 7.5-point physical worsening threshold established in pwRMS for MSIS-29v1 (Phillips et al., 2014).
METHODS: METHODS: Data from 2,589 participants of Phase III pivotal clinical trials—FENTREPID (NCT04544449, PPMS, n=957), GAVOTTE (NCT04548999, PPMS, n=768), and MUSETTE (NCT04544436, RMS, n=864)—were analyzed individually and as a pooled cohort. MWPC thresholds for MSIS-29v2 were estimated using anchor-based methods, supported by distribution-based methods. Anchor-based methods used the Patient Global Impression of Severity (PGI-S) as the anchor. We evaluated mean/median changes and empirical cumulative distribution function plots. Distribution-based methods used MSIS-29v2 baseline values to calculate standard deviations (0.2SD, 0.3SD, 0.5SD) and standard error of measurement. We analyzed worsening and improvement separately. Physical and psychological impact scales were examined respectively. Results were strengthened by triangulating findings with existing literature.
RESULTS: PGI-S demonstrated robust anchor quality for MSIS-29v2, with change from baseline correlations above 0.3. Anchor-based MWPC estimates for clinical worsening were 5.0 to 11.7 for the physical scale and 3.7 to 8.2 for the psychological scale. Anchor-based MWPC estimates for clinical improvement were -13.0 to -8.3 for the physical scale and -13.8 to -11.1 for the psychological scale. Distribution-based estimates were 4.0 to 12.7 for the physical scale and 4.7 to 12.5 for the psychological scale. Anchor-based worsening estimates were smaller in RMS than in PPMS.
CONCLUSIONS: This large-sample analysis of data from multiple clinical trials recommends that MWPC thresholds for both the MSIS-29v2 physical and psychological impact scales be a ≥8-point increase for worsening and a ≥10-point decrease for improvement. However, there was notable variability across estimates.
METHODS: METHODS: Data from 2,589 participants of Phase III pivotal clinical trials—FENTREPID (NCT04544449, PPMS, n=957), GAVOTTE (NCT04548999, PPMS, n=768), and MUSETTE (NCT04544436, RMS, n=864)—were analyzed individually and as a pooled cohort. MWPC thresholds for MSIS-29v2 were estimated using anchor-based methods, supported by distribution-based methods. Anchor-based methods used the Patient Global Impression of Severity (PGI-S) as the anchor. We evaluated mean/median changes and empirical cumulative distribution function plots. Distribution-based methods used MSIS-29v2 baseline values to calculate standard deviations (0.2SD, 0.3SD, 0.5SD) and standard error of measurement. We analyzed worsening and improvement separately. Physical and psychological impact scales were examined respectively. Results were strengthened by triangulating findings with existing literature.
RESULTS: PGI-S demonstrated robust anchor quality for MSIS-29v2, with change from baseline correlations above 0.3. Anchor-based MWPC estimates for clinical worsening were 5.0 to 11.7 for the physical scale and 3.7 to 8.2 for the psychological scale. Anchor-based MWPC estimates for clinical improvement were -13.0 to -8.3 for the physical scale and -13.8 to -11.1 for the psychological scale. Distribution-based estimates were 4.0 to 12.7 for the physical scale and 4.7 to 12.5 for the psychological scale. Anchor-based worsening estimates were smaller in RMS than in PPMS.
CONCLUSIONS: This large-sample analysis of data from multiple clinical trials recommends that MWPC thresholds for both the MSIS-29v2 physical and psychological impact scales be a ≥8-point increase for worsening and a ≥10-point decrease for improvement. However, there was notable variability across estimates.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
PCR74
Topic
Clinical Outcomes, Methodological & Statistical Research, Patient-Centered Research
Topic Subcategory
Instrument Development, Validation, & Translation, Patient-reported Outcomes & Quality of Life Outcomes
Disease
Neurological Disorders