The plots highlight the sample size per arm estimates required to observe 20-80% reductions in SBR change in a treated group compared to an untreated group in the striatal regions at 12, 24, and 48 months. Of note is the lower sample size requirements using VMAT2 PET than using DAT SPECT at the earlier timepoints. Despite much less VMAT2 PET data  than DAT SPECT data being available in the PPMI dataset, and therefore less accurate sample size estimates, it can be observed that fewer participants may be needed, and this observation is in line with the greater sensitivity of VMAT2 PET highlighted in our previously-published Resource.

The table also shows the sample size estimates per arm required to observe 20-80% reductions in SBR in a treated group compared to an untreated group. The table highlights that the putamen and striatum require fewer than 50 participants per arm to detect a 60% or 80% reduction of the observed SBR in a treated group compared to an untreated group after 24 months using DAT SPECT, and only after 12 months using VMAT2 PET. Even as early as 6 months, fewer than 50 subjects per arm may be required to observe a 80% slowing of the SBR changes in the putamen using VMAT2 PET (data not shown). As such, relatively quick insights into disease progression and potential therapeutic effects can be obtained using PIANO™-based DAT SPECT and VMAT2 PET SBR analysis.