TY  - JOUR
AU  - Germani, Massimiliano
AU  - Rebollo Mesa, Irene
AU  - Buchanan, Tim J
AU  - De Bruyn, Steven
AU  - Gasalla, Teresa
AU  - Van Tricht, Hans Lieve G
AU  - Ewen, Colin
AU  - Golbe, Lawrence I
AU  - Boxer, Adam
AU  - Höglinger, Günter
TI  - Combined Assessment of Function and Survival to Demonstrate the Effect of Treatment on Progressive Supranuclear Palsy.
JO  - Movement disorders
VL  - 40
IS  - 1
SN  - 0885-3185
CY  - New York, NY
PB  - Wiley
M1  - DZNE-2025-00228
SP  - 97 - 107
PY  - 2025
N1  - 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).
AB  - 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
KW  - Supranuclear Palsy, Progressive: drug therapy
KW  - Supranuclear Palsy, Progressive: physiopathology
KW  - Humans
KW  - Disease Progression
KW  - Male
KW  - Female
KW  - Treatment Outcome
KW  - Severity of Illness Index
KW  - Aged
KW  - clinical rating scale (Other)
KW  - item response theory (Other)
KW  - joint rank test (Other)
KW  - neurodegenerative disease (Other)
KW  - progressive supranuclear palsy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39470015
C2  - pmc:PMC11752988
DO  - DOI:10.1002/mds.30027
UR  - https://pub.dzne.de/record/276156
ER  -