Objective: 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).
Methods: 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.
Results: 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.
Conclusions: 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.
Statistics from Altmetric.com
▸ Supplementary data are published online only at http://jnnp.bmj.com/content/vol80/issue11
Funding BH acknowledges support from the Partners MS Center. RB acknowledges support of research grants from the National Institutes of Health (1R01NS055083-01) and National Multiple Sclerosis Society (RG3705A1; RG3798A2). Teva kindly accepted to use the placebo and treated data of the European/Canadian MRI trial of Copaxone in MS.
Competing interests None.
Ethics approval Ethics approval was obtained.
Provenance and Peer review Not commissioned; externally peer reviewed.