PIANO™ requires substantially lower sample sizes to assess reduction in observed atrophy compared to other quantitative analysis tools/methods.
Sample Sizes for PIANO™ Regional Atrophy
Sample size per arm required to observe 20-80% reduction of the regional atrophy in a treated group compared to an untreated group over a 12-month period.
Sample Sizes for PIANO™ Regional Volumes Compared to FreeSurfer
Sample size per arm required to observe 20%-80% reduction of the regional atrophy in a treated group compared to an untreated group over either a 6- or 12-month period using PIANO™ compared to the sample size calculations estimated using FreeSurfer over a 12-month period in equivalent neuroanatomical regions. The sample size estimations are color-coded, where the green hues are less than 50 subjects per arm.
The graph of sample size per arm vs. percent reduction in atrophy highlights a number of subcortical regions that require fewer than 50 subjects to detect a 40% reduction of the observed brain atrophy in a treated group compared to an untreated group.
The table shows the power calculations on both the 6- and 12-month timepoints, for the sample size per arm estimates required to observe 20%-80% reductions in atrophy in a treated group compared to an untreated group. Even as early as 6 months using our PIANO™ volume quantification in the Lateral Ventricles, Third Ventricle, Thalamus and Pallidum we require less than 50 subjects per arms to see 60% reduction of the observed brain atrophy, allowing for rapid insight into disease progression and potentially therapeutic effect.
We used FreeSurfer for comparative purposes because of its relative ubiquitous use by the academic community. Sample size calculations based on the 12-month timepoint volumes derived from Freesurfer shows substantially higher sample size requirements for the same regional volumes.
Interestingly, the planimetric measurement of MRPI and MRPI2.0, which are both widely used biomarkers to identify PSP subjects and show statistically significantover 6 and 12 months, require 2-3 times the sample size compared to the PIANO™ brainstem 3D volume assessments.