OBJECTIVES: Based on an 13-years experience (1999-2012) in collecting and analyzing real-world data for the Italian Regulatory Agency, CINECA Interuniversity Consortium has developed an innovative Cloud-based IT platform for the entire management of Performance-based Risk Sharing arrangements among Pharmaceutical Companies and Payers/Regulatory Authorities. The system has been used for more than 70 innovative drugs from eleven registries: oncology, diabetes, neurology, orphan drugs, rheumatology and others. More than 500.000 patients were registered by over 900 health structures (40.000 end-users) in a timeframe of seven years.  METHODS: Establish a unique and complete post-marketing safety surveillance and analysis system, used by Health Authorities (regional and national), Clinicians/Researchers and Payors which allows the management of performance-based risk-sharing arrangements (PBRSAs). The solution is designed to ensure proper data collection aimed to evaluate appropriateness , assess drug safety and estimate efficacy (automated procedures and calculations) in a real-world context.  Independently from the already existing solutions and organizational settings, the model allows to easily set-up ad-hoc procedures for data collections in any international context (multi-country and multi-language) supporting the implementation of PBRSAs for oncology (Payment by Results, Cost-Sharing and Risk-Sharing). RESULTS: The platform is able to manage any value-based scheme agreed between manufacturers and payers and it also may support drug combinations. By defining appropriate minimum datasets, with a limited effort, it is possible to involve all stakeholders obtaining systematic, homogeneous and high-quality data.  Example of trastuzumab and trastuzumab+pertuzumab combination will be reported. CONCLUSIONS: The introduction of an online integrated registry ensures the economic sustainability of innovative therapies and simplify their market access, while guaranteeing transparency of the whole process.  It also ensures treatment appropriateness, helps in monitoring drug consumption and related costs (better resources allocation), improves the real-time reporting of adverse events and allows the development of real-world datasets for scientific purposes.