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 observed atrophy highlights a number of cortical regions that require fewer than 50 subjects per arm to detect a 60% reduction of the observed brain atrophy.
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, less than 50 subjects per arm are estimated to be required to observe a 60% slowing of the observed brain atrophy in the lateral and third ventricles using PIANO™-based volumetric analysis. The sample size at 12 months requires fewer than 60 subjects to detect a 60% reduction of the observed brain atrophy across all regions. As such, relatively quick insights into disease progression and potential therapeutic effects can be obtained.
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 data for volumes derived from FreeSurfer show substantially higher sample size requirements for the same brain regions.