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Sample size requirements for treatment effects using gray matter, white matter and whole brain volume in relapsing-remitting multiple sclerosis
  1. Brian C Healy (bchealy{at}
  1. Brigham and Women's Hospital, Harvard Medical School, United States
    1. Paola Valsasina (valsasina.paola{at}
    1. Scientific Institute Ospedale San Raffaele, Italy
      1. Massimo Filippi (filippi.massimo{at}
      1. Scientific Institute Ospedale San Raffaele, Italy
        1. Rohit Bakshi (rbakshi{at}
        1. Brigham and Women's Hospital, Harvard Medical School, United States


          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 volume (BPV) as the 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, normalized GMV, normalized WMV and normalized BPV were analyzed using a random intercepts and slopes model to estimate the variance components and percent change. The required sample size to observe a 33%, 50% and 90% reduction in the percent change were calculated for each dataset using both a constant percent change for each measurement and the estimated percent change for each dataset.

          Results: The percent change was the greatest in GMV, but all variance components were smallest in BPV. Using the estimated percent 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 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 the treatment effect may be larger on GMV compared to BPV. However, GMV was somewhat limited by increased variability vs. BPV.

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