Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy

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. © 2016 International Parkinson and Movement Disorder Society