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@ARTICLE{Germani:276156,
      author       = {Germani, Massimiliano and Rebollo Mesa, Irene and Buchanan,
                      Tim J and De Bruyn, Steven and Gasalla, Teresa and Van
                      Tricht, Hans Lieve G and Ewen, Colin and Golbe, Lawrence I
                      and Boxer, Adam and Höglinger, Günter},
      title        = {{C}ombined {A}ssessment of {F}unction and {S}urvival to
                      {D}emonstrate the {E}ffect of {T}reatment on {P}rogressive
                      {S}upranuclear {P}alsy.},
      journal      = {Movement disorders},
      volume       = {40},
      number       = {1},
      issn         = {0885-3185},
      address      = {New York, NY},
      publisher    = {Wiley},
      reportid     = {DZNE-2025-00228},
      pages        = {97 - 107},
      year         = {2025},
      note         = {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).},
      abstract     = {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 $>80\%$ power to detect
                      significant treatment effects on the CAFS compared with
                      placebo. The CAFS provides good operating characteristics
                      and increased power to detect moderate treatment effects on
                      the PSP Rating Scale. We propose a trial design allowing
                      potential detection of treatment effects at a preplanned
                      interim analysis after participants complete 12 months of
                      treatment, with assessment of effects of treatment (≤24
                      months) on survival.Use of the CAFS could provide a
                      comprehensive and robust estimate of the clinical benefit of
                      future therapies. © 2024 UCB. Movement Disorders published
                      by Wiley Periodicals LLC on behalf of International
                      Parkinson and Movement Disorder Society.},
      keywords     = {Supranuclear Palsy, Progressive: drug therapy /
                      Supranuclear Palsy, Progressive: physiopathology / Humans /
                      Disease Progression / Male / Female / Treatment Outcome /
                      Severity of Illness Index / Aged / clinical rating scale
                      (Other) / item response theory (Other) / joint rank test
                      (Other) / neurodegenerative disease (Other) / progressive
                      supranuclear palsy (Other)},
      cin          = {Clinical Research (Munich)},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39470015},
      pmc          = {pmc:PMC11752988},
      doi          = {10.1002/mds.30027},
      url          = {https://pub.dzne.de/record/276156},
}