title: Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials.
abstract: Clinical and MRI measurements can track disease progression in PSP, but many have not been extensively evaluated in multicenter clinical trials. We identified optimal measures to capture clinical decline and predict disease progression in multicenter PSP trials.
  
  
  
  Longitudinal clinical rating scales, neuropsychological test scores, and volumetric MRI data from an international, phase 2/3 clinical trial of davunetide for PSP (intent to treat population, n = 303) were used to identify measurements with largest effect size, strongest correlation with clinical change, and best ability to predict dropout or clinical decline over one year as measured by PSP Rating Scale (PSPRS).
  
  
  
  Baseline cognition as measured by Repeatable Battery for Assessing Neuropsychological Status (RBANS) was associated with attrition, but had only a small effect. PSPRS and Clinical Global Impression (CGI) had the largest effect size for measuring change. Annual change in CGI, RBANS, color trails, and MRI midbrain and ventricular volumes were most strongly correlated with annual PSPRS and had the largest effect sizes for detecting annual change. At baseline, shorter disease duration, more severe depression, and lower performance on RBANS and executive function tests were associated with faster worsening of the PSPRS in completers. With dropouts included, SEADL, RBANS, and executive function tests had significant effect on PSPRS trajectory of change.
  
  
  
  Baseline cognitive status and mood influence the rate of disease progression in PSP. Multiple clinical, neuropsychological, and volumetric MRI measurements are sensitive to change over one year in PSP and appropriate for use in multicenter clinical trials.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, USA 94158.
authors.forename: Jee
authors.initials: J
authors.lastname: Bang
authors.affiliation: Department of Epidemiology and Biostatistics, Division of Biostatistics, University of California San Francisco, 550 16th Street, San Francisco, CA, USA 94158. iryna.lobach@ucsf.edu.
authors.forename: Iryna V
authors.initials: IV
authors.lastname: Lobach
authors.affiliation: Department of Neurology, University of Toronto, 399 Bathurst St, McLaughlin 7-418, Toronto, ON, M5T 2S8, Canada. lang@uhnresearch.ca.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.affiliation: Department of Neurology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, USA 19104. mgrossma@mail.med.upenn.edu.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.affiliation: Department of Neurology, Mayo Clinic, 200 1st St SW, Rochester, MN, USA 55905. knopman@mayo.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, USA 94158.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Department of Psychiatry and the Behavioral Sciences and Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. lschneid@usc.edu.
authors.forename: Lon S
authors.initials: LS
authors.lastname: Schneider
authors.affiliation: Department of Neurology, Baylor College of Medicine, 6550 Fannin St # 1801, Houston, TX, USA 77030. rdoody@bcm.edu.
authors.forename: Rachelle S
authors.initials: RS
authors.lastname: Doody
authors.affiliation: Institute of Neurology, University College of London, 1 Wakefield Street - London - WC1N 1PJ, UK. alees@ion.ucl.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.affiliation: UCB BioSciences, Research Triangle, NC, USA. michael.gold.md@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Gold
authors.affiliation: Celerion, 621 Rose St, Lincoln, NE 68502, USA. bhmorimoto@gmail.com.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Morimoto
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, USA 94158.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Boxer
mesh_terms: D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data*; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011379:Prognosis; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology
keywords: Clinical trial methodology; Progressive supranuclear palsy