Detecting treatment effects on brain atrophy in relapsing remitting multiple sclerosis: sample size estimates

Area of Science:

• Neurology
• Radiology
• Clinical Trials

Background:

• Brain atrophy, indicative of neuroaxonal degeneration, is a key indicator of multiple sclerosis (MS) progression.
• Objective MRI-based measures of brain atrophy are crucial for assessing disease-modifying treatments in relapsing-remitting MS (RRMS).

Purpose of the Study:

• To estimate sample sizes for placebo-controlled trials in RRMS using brain atrophy as an outcome.
• To investigate the impact of atrophy measurement methods and trial duration on required sample sizes.

Main Methods:

• T1-weighted volumetric MRI scans were acquired from 33 RRMS patients and 16 controls.
• Brain atrophy was quantified using four methods: segmented brain volume difference, BBSI, SIENA, and ventricular enlargement.
• Linear mixed models and sample size calculations were performed based on estimated mean and variance.

Main Results:

• For a 2-year trial, a 30% treatment effect required 123 subjects per arm with SIENA, 157 with BBSI, 140 with ventricular enlargement, and 763 with segmented brain volume difference.
• Longer trial durations significantly reduced sample size requirements for a given effect size and measurement method.

Conclusions:

• Brain atrophy measurements offer a valuable, objective outcome measure for monitoring treatment efficacy in RRMS clinical trials.
• Further research is needed to explore the link between atrophy and disability, and to address potential confounding factors in atrophy measurement.