Experimental design and sample size considerations in longitudinal magnetic resonance imaging-based biomarker...

Several modeling approaches have been developed to quantify differences in multiple sclerosis lesion evolution on magnetic resonance imaging to identify the effect of treatment on disease progression. These studies have limited clinical applicability due to onerous scan frequency and lengthy study duration. Efficient methods are needed to reduce the required sample size, study duration, and sampling frequency in longitudinal magnetic resonance imaging studies. We develop a data-driven approach to identify parameters of study design for evaluation of longitudinal magnetic resonance imaging biomarkers of multiple sclerosis lesion evolution. Our design strategies are considerably shorter than those described in previous studies, thus having the potential to lower costs of clinical trials. From a dataset of 36 multiple sclerosis patients with at least six monthly magnetic resonance imagings, we extracted new lesions and performed principal component analysis to estimate a biomarker that recapitulated lesion recovery. We tested the effect of multiple sclerosis disease modifying therapy on the lesion evolution index in three experimental designs and calculated sample sizes needed to appropriately power studies. Our proposed methods can be used to calculate required sample size and scan frequency in observational studies of multiple sclerosis disease progression as well as in designing clinical trials to find effects of treatment on multiple sclerosis lesion evolution.