PRIMUS: a precision medicine platform reusing clinical trials and registry data to support treatment selection in multiple sclerosis

Objectives: The "Projections In Multiple Sclerosis" (PRIMUS) project aims to develop a precision medicine platform enabling neurologists to support therapeutic decisions in multiple sclerosis by visualizing similar patient data in a reference database. We present a data integration method to combine randomized clinical trials (RCTs) and observational studies data and optimize the informativeness of the resulting database. Material and Methods: We developed an extract-transform-load data integration pipeline to combine 13 source databases: the "mother" and "high-definition" cohorts from the French MS registry and 11 industrial RCTs (31 786 patients). We aimed to inform each treatment class initiation with at least 500 patients with a 2-year clinical and MRI follow-up. Our data integration strategy used every patient visit as a potential baseline time point to inform a specific neurologist' query to the platform, thus tailoring the actual analysis cohort to each visiting patient. Results: The PRIMUS database had 12 953 patients with at least one informative visit, using the per-visit integration. It could inform treatment initiation scenarios with at least 485 patients for glatiramer acetate and at most 1754 for natalizumab. For instance, our per-visit integration method identified 1306 patients in the high-definition cohort against 610 with the classical epidemiological per-patient integration. Although the mother cohort's longitudinal data were deemed sparse, we identified 6128 informative patients. Discussion: Neurologists would query the PRIMUS database through a web application to support discussions with their patients and the selection of disease-modifying treatments. Conclusion: Our data integration pipeline enabled the creation of a highly informative reference database.