We are delighted to be conversing with Prof Dani Prieto-Alhambra, Professor of Pharmaco and Device Epidemology, NDORMS, University of Oxford, UK, and part-time Professor of Real World Evidence, Erasmus MC, Rotterdam, and Research Coordinator for EHDEN. In this penultimate episode of season 2, Dani returns to the podcast (he also was in episode #2 of season 1) to discuss his perspective on evidence generation and conducting research with real world data today and a vision for tomorrow. We start with exploring the differences (or not) between pharmaco and device epidemiology from Dani's experience, then go on to re-evaluating the research response to the COVID-19 pandemic, including inherent difficulties, and in particular evolving research in areas such as 'Long COVID' and sub-acute COVID that his group is leading. Clearly, there are implications for not only COVID-19, for e.g., vaccine use and safety, but also more widely for medical and health research, and in catching up with much that was challenged due to the pandemic. We cover the upcoming research priorities, inclusive of plans for study-a-thons and evidence-a-thons in EHDEN, based on a call for study  proposals within the programme. Following this Dani outlines how he sees research methods and collaborations changing now, for the better, and hopefully permanently, in using federated networks, distributed network analysis across geographies, supported by new platforms and technologies. He goes on to explain the use of study-a-thons and evidence-a-thons in EHDEN and OHDSI, and their emerging role in rapid analysis work to meet the challenge of responding to diverse research needs. In the last third of this episode we discuss the paradigm shift we are seeing in terms of the creative disruption of the open science agenda and OHDSI research framework in EHDEN, in Europe, but also globally, inclusive of the Global South. Specific challenges such as reproducibility and transparency are also coming to the fore with our new methods in being able to be truly open, and with a need to collaborate. We take Dani back to his first exposure to OHDSI, the positive impact on his own career, but also the need to train and support a new generation of researchers where this paradigm shift today will be routine for them tomorrow. Moreover, and with COVID-19 in mind, we have changed science for the better, but we need to reinvigorate faith from certain communities in science globally. The views expressed by the participants are personal and not necessarily reflective of their organisations.