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@ARTICLE{Yousefi:272867,
      author       = {Yousefi, Elham and Gewily, Mohamed and König, Franz and
                      Höglinger, Günter and Hopfner, Franziska and Karlsson,
                      Mats O and Ristl, Robin and Zehetmayer, Sonja and Posch,
                      Martin},
      title        = {{E}fficiency of multivariate tests in trials in progressive
                      supranuclear palsy.},
      journal      = {Scientific reports},
      volume       = {14},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2024-01284},
      pages        = {25581},
      year         = {2024},
      abstract     = {Measuring disease progression in clinical trials for
                      testing novel treatments for multifaceted diseases as
                      progressive supranuclear palsy (PSP), remains challenging.
                      In this study we assess a range of statistical approaches to
                      compare outcomes as measured by the items of the progressive
                      supranuclear palsy rating scale (PSPRS). We consider several
                      statistical approaches, including sum scores, a modified
                      PSPRS rating scale that had been recommended by FDA in a
                      pre-IND meeting, multivariate tests, and analysis approaches
                      based on multiple comparisons of the individual items. In
                      addition, we propose two novel approaches which measure
                      disease status based on Item Response Theory models. We
                      assess the performance of these tests under various
                      scenarios in an extensive simulation study and illustrate
                      their use with a re-analysis of the ABBV-8E12 clinical
                      trial. Furthermore, we discuss the impact of the
                      FDA-recommended scoring of item scores on the power of the
                      statistical tests. We find that classical approaches as the
                      PSPRS sum score demonstrate moderate to high power when
                      treatment effects are consistent across the individual
                      items. The tests based on Item Response Theory (IRT) models
                      yield the highest power when the simulated data are
                      generated from an IRT model. The multiple testing based
                      approaches have a higher power in settings where the
                      treatment effect is limited to certain domains or items. The
                      study demonstrates that there is no one-size-fits-all
                      testing procedure for evaluating treatment effects using
                      PSPRS items; the optimal method varies based on the specific
                      effect size patterns. The efficiency of the PSPRS sum score,
                      while generally robust and straightforward to apply, varies
                      depending on the specific patterns of effect sizes
                      encountered and more powerful alternatives are available in
                      specific settings. These findings can have important
                      implications for the design of future clinical trials in PSP
                      and similar multifaceted diseases.},
      keywords     = {Supranuclear Palsy, Progressive: diagnosis / Humans /
                      Multivariate Analysis / Clinical Trials as Topic / Disease
                      Progression / Clinical trials (Other) / Item response theory
                      (Other) / Multiple endpoints (Other) / Multivariate tests
                      (Other) / Progressive supranuclear palsy (Other) /
                      Simulation study (Other)},
      cin          = {Clinical Research (Munich) / AG Höglinger},
      ddc          = {600},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1110002},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC11514033},
      pubmed       = {pmid:39462124},
      doi          = {10.1038/s41598-024-76668-4},
      url          = {https://pub.dzne.de/record/272867},
}