BackgroundReal-world evidence (RWE) plays a key role in regulatory and healthcare decision-making, but the potentially fragmentated nature of generated evidence may limit its utility for clinical decision-making. Heterogeneity and a lack of reproducibility in RWE resulting from inconsistent application of methodologies across data sources should be minimized through harmonization.MethodsThis paper’s aim is to describe and reflect upon a multidisciplinary research platform (FOUNTAIN; FinerenOne mUlti-database NeTwork for evidence generAtIoN) with coordinated studies using diverse RWE generation approaches and explore the platform’s strengths and limitations. With guidance from an executive advisory committee of multidisciplinary experts and patient representatives, the goal of the FOUNTAIN platform is to harmonize RWE generation across a portfolio of research projects, including research partner collaborations and a common data model (CDM)–based program. FOUNTAIN’s overarching objectives as a research platform are to establish long-term collaborations among pharmacoepidemiology research partners and experts and to integrate diverse approaches for RWE generation, including global protocol execution by research partners in local data sources and common protocol execution in multiple data sources through federated data networks, while ensuring harmonization of medical definitions, methodology, and reproducible artifacts across all studies. Specifically, the aim of the multiple studies run within the frame of FOUNTAIN is to provide insight into the real-world utilization, effectiveness, and safety of finerenone across its life-cycle.ResultsCurrently, the FOUNTAIN platform includes 9 research partner collaborations and 8 CDM-mapped data sources from 7 countries (United States, United Kingdom, China, Japan, The Netherlands, Spain, and Denmark). These databases and research partners were selected after a feasibility fit-for-purpose evaluation. Six multicountry, multidatabase, cohort studies are ongoing to describe patient populations, current standard of care, comorbidity profiles, healthcare resource use, and treatment effectiveness and safety in different patient populations with chronic kidney disease and type 2 diabetes. Strengths and potential limitations of FOUNTAIN are described in the context of valid RWE generation.ConclusionThe establishment of the FOUNTAIN platform has allowed harmonized execution of multiple studies, promoting consistency both within individual studies that employ multiple data sources and across all studies run within the platform’s framework. FOUNTAIN presents a proposal to efficiently improve the consistency and generalizability of RWE on finerenone.