Multiple Sclerosis: insights on COVID-19, treatments and inequalities

This thesis presents a collection of projects on multiple sclerosis (MS), divided into three sections according to the main focus: COVID-19, treatments and inequalities. These three topics are highly interrelated: MS research during the pandemic principally focused on the impact of MS therapies, COVID-19 crisis exacerbated inequalities, disparities can be found in early access to therapies and representativeness in clinical trials. Part of the works on COVID-19 explored data from the MuSC-19 platform, where information on COVID-19 infections among patients with MS were collected. In particular, risk factors for worse course of COVID-19 were studied, in still unexplored settings or using advanced statistical methodologies, including mixture analysis and several variable selection approaches. Additionally, three surveys were conducted to explore patients’ adherence to lockdown recommendations and opinions on telemedicine and to study digital work engagement of neurologists. COVID-19 pandemic speeded up the digital transformation process and findings from these surveys can surely help to direct interventions. Two articles were presented in the section on MS and treatments, with special emphasis on statistical methodology. First, a randomized clinical trial was emulated, leading to similar results compared to the original study. Second, bayesian approach was used to overcome the sample size problem in pediatric clinical trials. These studies emphasized the importance of real-word evidence in the context of rigorous target trial emulation and the utility of advanced statistical approaches to solve common issues of standard study designs. Finally, in the last section, the systematic review on race and ethnicity in MS clinical trials highlighted the need of more efforts to accurately collect and report data that adequately represent minoritized racial and ethnical groups, already at a design phase. Moreover, statistical considerations to correctly explore the variable ‘race’ were provided, adequately unpacking the concepts of race and racism. Finally, the SocialMS study aims to provide a comprehensive overview of social determinants of health (SDOH) in the Italian MS context, with special emphasis on interrelation among SDOH, influence of SDOH on MS-related outcomes and impact of MS itself on worse SDOH. Evidence from this study can surely help to direct potential individual and structural interventions.