Modeling the Distribution of New MRI Cortical Lesions in Multiple Sclerosis Longitudinal Studies

OBJECTIVE Recent studies have shown the relevance of the cerebral grey matter involvement in multiple sclerosis (MS). The number of new cortical lesions (CLs), detected by specific MRI sequences, has the potential to become a new research outcome in longitudinal MS studies. Aim of this study is to define the statistical model better describing the distribution of new CLs developed over 12 and 24 months in patients with relapsing-remitting (RR) MS. METHODS Four different models were tested (the Poisson, the Negative Binomial, the zero-inflated Poisson and the zero-inflated Negative Binomial) on a group of 191 RRMS patients untreated or treated with 3 different disease modifying therapies. Sample size for clinical trials based on this new outcome measure were estimated by a bootstrap resampling technique. RESULTS The zero-inflated Poisson model gave the best fit, according to the Akaike criterion to the observed distribution of new CLs developed over 12 and 24 months both in each treatment group and in the whole RRMS patients group adjusting for treatment effect. CONCLUSIONS The sample size calculations based on the zero-inflated Poisson model indicate that randomized clinical trials using this new MRI marker as an outcome are feasible.