Mental, neurological and substance-use disorders (MNS) constitute 13% of the global disease burden, surpassing both cardiovascular diseases and cancers. Three types of studies may yield insightful data to guide the improvement of clinical care of severe mental illnesses. First, cohort studies are needed to analyze the illness trajectories of severe mental illnesses. The FACE-SZ cohort has been created in 2010 and has yielded important data on the trajectory of schizophrenia. More specifically, the staging model conceptualized in psychiatry 25 years ago has been confirmed and developed. Pierre-Michel Llorca will present the cohort and major recent findings including some modifiable factors of poor prognosis and relapse prevention that have been identified and may change our vision of schizophrenia as an irreversible neuroprogressive illness. Second, French national databases are now available to analyze epidemiologic events at a national level. Laurent Boyer will present recent findings on the French hospital national database (PMSI) on the somatic care of SZ subjects (with a focus on trauma, perinatal and end-of-life cancer hospitalizations). Last but not least, systematic reviews and meta-analyses have become indispensable methods for the evaluation of medical treatments. Stefan Leucht will present the results of recent meta-analyses about the treatment of schizophrenia. These will comprise a network meta-analysis of antipsychotic drugs compared with each other and new findings on relapse prevention. Methodological problems of current trials will also be addressed.