EU-PEARL: Changing the paradigm of clinical trials in Europe

Abstract

Abstract Issue Recently, innovative clinical trial designs have been proposed, which have the potential to revolutionize clinical research. Whereas classical trials mostly evaluate only one investigational drug, platform trials embed various trials under a shared master protocol to enable the evaluation of multiple interventions for a disease or condition. Platform trials have mostly been used to evaluate cancer therapies, but also recently for COVID-19. The EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project aims to expand the use of platform trials as the backbone of drug development. Description of Issue EU-PEARL is a Innovative Medicines Initiative 2 Joint Undertaking funded project (2019-2023), and a strategic public and private sector alliance, which aims to support the transformation of the classical trial approach into a cross-company collaborative, multi-compound platform, centred around patients, not diseases. How to operationalize and sustain this? A multi-stakeholder, mixed-methods approach is taken, focused around the concept of an integrated research platform (IRP), i.e., a common enabling framework for platform trials. The IRP will be established as a sustainable and scalable global solution, consisting of an infrastructure, workflows, and guidance on how to meet complex regulatory, ethical, legal, statistical and data requirements. Lessons from COVID-19 trials will be incorporated. Results A disease-agnostic IRP is being developed, as well as four disease specific IRPs in four areas of high public health relevance, i.e. major depressive disorder, tuberculosis, non-alcoholic steatohepatitis, and neurofibromatosis. Lessons Multi-stakeholder, multi-sector and multi-disciplinary collaborations are challenging in practice, but rewarding in outcomes. Given the complexity of setting-up these novel trials, clear communication and standardized terminology must be established, as well as continual awareness building of their components, challenges and benefits. Key messages EU-PEARL intends to stage the clinical trials of the future, which will be more adaptive, efficient and patient-centred by design and outcome. EU-PEARĹs efforts aim to contribute to timely societal access to affordable medicines and address unmet health needs.