Integration of Real-World Data into Clinical Trials: An Interdisciplinary Discussion from Regulatory and Practical Perspectives

Increasing efforts are required to integrate the growing volume of so-called real-world data (also named routine practice data), which are data generated outside of randomized controlled trials, into regulatory studies. Various stakeholders anticipate that such integration could save time and financial resources during the approval process of new therapies, and ethical considerations also partially support such an approach. The aim of this manuscript is to provide an overview of the methodological, ethical, and regulatory considerations when integrating routine practice data into randomized controlled trials. It targets clinical researchers, biostatisticians, regulators, and decision-makers involved in evidence generation and trial design.The inclusion of real-world data in randomized controlled trials can be meaningful from both ethical and economic perspectives. However, implementing this requires addressing various and sometimes significant limitations of the data, which need to be methodologically addressed. Therefore, it is essential to carefully weigh the risks and benefits of incorporating real world data into clinical studies.Randomized trials remain the gold standard for evaluating the efficacy of new therapies. Nevertheless, real-world data have the potential to improve the complex and costly process of drug development. The assessment of the potential for a specific clinical study should be made in collaboration with all relevant stakeholders. Apart from that, real-world data have a substantial potential to expand the evidence from randomized trials after post-market approval, thereby ensuring the safety of all patients.