Maria Stamelou1,2,3, Jakob Schöpe4, Stefan Wagenpfeil4, Teodoro Del Ser5,6, Jee Bang7, Iryna Y Lobach7, Phi Luong7, Gesine Respondek7, Wolfgang H Oertel1, AdamL Boxer7, Günter U Höglinger1,8,9. 1. Department of Neurology, Philipps University, Marburg, Germany. 2. Second Department of Neurology, Attikon University Hospital, University of Athens, Athens, Greece. 3. Movement Disorders Department, Hygeia Hospital, Athens, Greece. 4. Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Campus Homburg, Homburg, Germany. 5. Medical Department, Noscira SA, Madrid, Spain. 6. Alzheimer Project Research Unit, Fundación CIEN, Madrid, Spain. 7. Memory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA. 8. Department of Neurology, Technische Universität München, Munich, Germany. 9. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Abstract
BACKGROUND: Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. METHODS: We provide sample size calculations based on data collected in 187 PSP patients assigned to placebo in these trials. A placebo effect was calculated. RESULTS: The total PSP-Rating Scale required the least number of patients per group (N = 51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. CONCLUSIONS: We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome.
BACKGROUND: Two recent randomized, placebo-controlled trials of putative disease-modifying agents (davunetide, tideglusib) in progressive supranuclear palsy (PSP) failed to show efficacy, but generated data relevant for future trials. METHODS: We provide sample size calculations based on data collected in 187 PSPpatients assigned to placebo in these trials. A placebo effect was calculated. RESULTS: The total PSP-Rating Scale required the least number of patients per group (N = 51) to detect a 50% change in the 1-year progression and 39 when including patients with ≤ 5 years disease duration. The Schwab and England Activities of Daily Living required 70 patients per group and was highly correlated with the PSP-Rating Scale. A placebo effect was not detected in these scales. CONCLUSIONS: We propose the 1-year PSP-Rating Scale score change as the single primary readout in clinical neuroprotective or disease-modifying trials. The Schwab and England Activities of Daily Living could be used as a secondary outcome.
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