Sample size requirements for treatment effects using gray matter, white matter and whole brain volume in...

To compare the sample size requirements for a neuroprotection trial with change in cerebral gray matter volume (GMV), white matter volume (WMV) or whole brain parenchymal volume (BPV) as outcome measures in patients with relapsing-remitting multiple sclerosis (RRMS).

Two datasets with longitudinal MRI measures of untreated patients with RRMS (n = 116 and n = 26) and one dataset of treated patients with RRMS (n = 109) were investigated. In each dataset, normalised GMV, normalised WMV and normalised BPV were analysed using a random intercepts and slopes model to estimate the variance components and per cent change. The required sample size to observe a 33%, 50% and 90% reduction in the per cent change was calculated for each dataset using both a constant per cent change for each measurement and the estimated per cent change for each dataset.

The per cent change was greatest in GMV but all variance components were smallest in BPV. Using the estimated per cent change, the sample size required in the untreated cohorts was similar for GMV and BPV, and both were lower than WMV. In the treated cohort, the sample size for GMV was the smallest of all measures. Including additional scans reduced the sample size but increasing the length of the trial and clustering scans led to greater reductions.

Cerebral GMV may be a viable outcome measure for clinical trials investigating neuroprotection in RRMS patients, especially considering that the treatment effect may be larger on GMV compared with BPV. However, GMV was somewhat limited by increased variability versus BPV.