%0 Journal Article
%A Germani, Massimiliano
%A Rebollo Mesa, Irene
%A Buchanan, Tim J
%A De Bruyn, Steven
%A Gasalla, Teresa
%A Van Tricht, Hans Lieve G
%A Ewen, Colin
%A Golbe, Lawrence I
%A Boxer, Adam
%A Höglinger, Günter
%T Combined Assessment of Function and Survival to Demonstrate the Effect of Treatment on Progressive Supranuclear Palsy.
%J Movement disorders
%V 40
%N 1
%@ 0885-3185
%C New York, NY
%I Wiley
%M DZNE-2025-00228
%P 97 - 107
%D 2025
%Z This research was funded by UCB. G.H. was supported by the European Joint Programme on Rare Diseases (Improve-PSP) and the Deutsche Forschungsgemeinschaft DFG, (German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy ID 390857198).
%X Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease-modifying treatments. Recent trials of potential therapies had durations of 12 months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error. Selecting efficacy measures more sensitive to disease modification may facilitate identification of treatment effect.The objective of this study was to evaluate the simulated phase 3 PSP trial assessing the effect of disease-modifying intervention on a novel combined primary endpoint comprising function (PSP Rating Scale) and survival, the Combined Assessment of Function and Survival (CAFS), and to determine operating characteristics of the CAFS.To simulate PSP progression in the trial population, we developed models of PSP Rating Scale and survival using data from published clinical studies. These models were used to define operating characteristics of the CAFS for use in a phase 3 trial.The sample size determined (N = 384; 1:1 randomization) would provide >80
%K Supranuclear Palsy, Progressive: drug therapy
%K Supranuclear Palsy, Progressive: physiopathology
%K Humans
%K Disease Progression
%K Male
%K Female
%K Treatment Outcome
%K Severity of Illness Index
%K Aged
%K clinical rating scale (Other)
%K item response theory (Other)
%K joint rank test (Other)
%K neurodegenerative disease (Other)
%K progressive supranuclear palsy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39470015
%2 pmc:PMC11752988
%R 10.1002/mds.30027
%U https://pub.dzne.de/record/276156