Quantitative Comparisons of Progressive Supranuclear Palsy Rating Scale Versions Using Item Response Theory

Background Progressive supranuclear palsy (PSP) is a neurodegenerative, late‐onset disease that is challenging in terms of assessment. The Progressive Supranuclear Palsy Rating Scale (PSPRS), a 28‐item clinician‐reported scale, is the most established clinical outcome assessment method. Recently, the U.S. Food and Drug Administration (FDA) has proposed a subscale of 10 items as an alternative to full PSPRS. Objectives To quantitatively evaluate and compare the properties of full PSPRS and the FDA subscale using item response theory. To develop a progression model of the disease and assess relative merits of study designs and analysis options. Methods Data of 979 patients from four interventional trials and two registries were available for analysis. Our investigation was divided into: (1) estimating informativeness of the 28 items; (2) estimating disease progression; and (3) comparing the scales, trial designs, and analysis options with respect to power to detect a clinically relevant treatment effect. Results PSPRS item scores had a low pairwise correlation (r = 0.17 ± 0.14) and the items irritability, sleep difficulty, and postural tremor were uncorrelated with the other items. The FDA‐selected items displayed higher correlation (r = 0.35 ± 0.14) and were the basis for a longitudinal item response model including disease progression. Trial simulations indicated that identification of a disease‐modifying treatment effect required less than half the study size if the analysis was based on longitudinal item information compared with total scores at end‐of‐treatment. Conclusion A longitudinal item response model based on the FDA‐selected PSPRS items is a promising tool in evaluating treatments for PSP. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.