Project

Patient-centricity is increasingly recognised as a priority in research and development of medicines and a founding principle of the common values in European Union Health Systems. The patient’s voice underpins Research and Development (R&D) of new medicines towards better health outcomes.

In order to build and reinforce partnerships between patients and researchers, current practices need to evolve. The basis of a successful patient research partnership requires both the ability of researchers to engage meaningfully with patients, and their ability to contribute proactively and meaningfully with researchers, both from industry and from academia. The patients’ contribution focus on providing high quality cross-disease or disease-specific knowledge, as well as expertise to guide and refine research priorities, development and assessment processes. The different stakeholders involved in medicine development widely acknowledge that innovative approaches, creative thinking and robust, trusted and ethical practices are necessary to orientate research and medicines development towards better patient health outcomes.

In principle, patient-centricity is on everyone’s agenda, but the means and methods are often lacking or disparate inducing a lack of effective operationalisation. The adoption of a patient-centred approach and meaningful patient engagement in medicines R&D varies greatly across countries and across disease areas. The R&D system has to become more responsive and responsible. The transformation from a linear development system, into one that focuses on societal impact and the active involvement of civil society in the R&D process, is called Responsible Research and Innovation. RRI is gaining ground, especially within the European Commission.

Patients have different perceptions to clinicians or researchers about what innovations would bring most value to their lives. Their early engagement is key to ensure consideration of patients’ views when identifying the research topic and when defining questions and overall trial design, especially in the context of IRP trials that add further levels of complexity. It is because of this that patient engagement drives the patient-centredness approach in research. EU-PEARL will facilitate structured, systematic and sustainable patient engagement around three key principles:

– patient education and training (connecting with IMI EUPATI);
– guidance on engagement (connecting with IMI PARADIGM and the Patient Focused Medicines Development (PFMD) initiative); and
– sustainability of patient engagement in terms of concept, resources and process.

By working on the convergence of all three aspects in the EU-PEARL structure, we are embedding patient engagement in the design of the IRPs framework.

EU-PEARL partner European Patients’ Forum (EPF) an umbrella patient organisation that works with patients’ groups in public health across Europe, co-ordinates the patients’ perspectives and ensure the provision of deep cross-disease or disease-specific knowledge, as well as expertise to guide and refine research priorities and outcome measures from patients’ perspectives. EU-PEARL represents the perfect vehicle to structurally embed patients in the process of clinical R&D and to engage with Responsible Research and Innovation (RRI) practices.

EU PEARL plans to establish a Patient Engagement Platform as an online portal with resources to support patient and public awareness about IRP trials. This platform will ultimately facilitate the creation of partnership and early engagement of patients and patient associations in the design of clinical trials, placing the patients in the centre of the process, centralising the initiatives of patient engagement in research clinical trials and making them visible to the public.

The Patient Engagement Platform will be led by patients, built on established patient networks, providing a match-making system between the patients and the patient engagement opportunities in the design of clinical trials. Educational group workshops where both clinicians and patients actively learn from each other resulting in patients’ more active engagement will also be delivered at the early stages of the project.

Patient-centric adaptive IRP trials are widely considered the future of clinical development as they provide clear advantages for patients, industry and healthcare systems. However, such platform trials require intensive collaboration between and amongst the biopharmaceutical industry and public institutions. EU-PEARL will collaborate with the European University Hospital Alliance (EUHA), established in April 2017. The EUHA boasts over 30,000 publications and more than 8,000 active clinical trials per year.

EUHA partners in EU-PEARL include Assistance Publique – Hôpitaux de Paris (AP-HP) (link to partner text), Charité Universitätsmedizin Berlin (link to partner text), the Erasmus Medical Centre Rotterdam (EMC) (link to partner text), the Vienna General Hospital (MUW) (link to partner text), the San Raffaele Hospital Milan (USR) (link to partner text), the King’s College London (KCL) (link to partner text), the Universitair Ziekenhuis Leuven (KU Leuven) (link to partner text) and the University Hospital Campus Vall d’Hebron Barcelona (VHIR) (link to partner text).

The EUHA alliance was established with the goal of advancing the state of the art in research-intensive healthcare. Many institutions have been accredited by the European Clinical Research Infrastructure Network (ECRIN), the European Research Infrastructure dedicated to facilitating multi-national clinical trials and as they are connected to the InSite Platform, they are well positioned to rapidly adopt the IRP framework developed by EU-PEARL.

Designing methodologically sound protocols to generate statistically valid results whilst evaluating multiple treatments in parallel is a paramount objective within EU-PEARL. The challenges, including regulatory acceptance of these data, are being addressed by timely engagement with all relevant stakeholders by the leading experts in the consortium. EU-PEARL remains aligned with existing efforts such as IMI EPAD and IMI EHDEN projects and will build upon existing know-how within EUHA and ECRIN.

The common set of processes and methodologies will facilitate extension of the design to other disease areas to make the IRPs sustainable. EU-PEARL plans to engage with regulators such as EMA and FDA and other decision makers to promote the IRP concept, involve them in requirements setting and in defining acceptance criteria for the methodologies and analyses conducted in IRPs.

The current capability of the InSite Platform) to connect to hospitals EHRs systems will be extended to provide the ability to connect to other sources of electronic health records, from observational and registries data bases. The new capabilities will upgrade the ability to conduct Natural Disease History analysis and enable patient recruitments for platform trials.

EU-PEARL encourages the use of emerging standards in sharing EHR data and implement these standards with EU-PEARL partners in close collaboration with other IMI projects ( EHDEN , EMIF , etc). EU-PEARL does not intend to develop new standards for sharing observational data. EU-PEARL is set to adopting and/or define principles, policies, and codes of practice, quality guidelines and standard operating procedures consistently for all consortium partners and any external data access providers within the IRP network.

EU PEARL will ensure that the collection and inclusion, processing and use of health and wellness data across the consortium complies with European and national data protection regulations and legislation (including the GDPR and national implementations, and the forthcoming ePrivacy regulation) and with Good Clinical Practice (GCP). Existing information, governance resources and data sharing from IMI/EU initiatives ( EHR4CR , EMIF , CORBEL , EOSC-Life , ECRIN i~HD , GO-FAIR , EHDEN and others) to which members of this consortium have contributed, are meant to be the basis for specification of the necessary project instruments. This will allow us to rapidly apply the policies and procedures necessary to begin sharing and working with data access providers, and then to define more specialised instruments as needed.

Specifically, WP3 is aligning with relevant initiatives to build further on the EIT Health EHR2EDC project facilitating the efficient and trustworthy reuse of EHR data into Electronic Data Capture (EDC) systems, and on EOSC-Life/ECRIN work on ethical and data protection requirements for secondary use of data EU countries. WP3 is leveraging and developing interactions initiated with standards organisations bodies, HL7, CDISC and IHE, as part of the EIT Health EHR2EDC project to facilitate re-use of existing interoperability mapping resources and avoid duplicative and competing efforts.

Finally, EU-PEARL aims to leverage the extensive experience of the EUHA network of hospitals in using observational data and complement it with the i~HD data quality assessment methodology. This pillar also encompasses the legal framework that is needed to permit public and private partners to share information about compounds in development, as well as trial protocols and data, and insights derived from the data and strategies for regulatory approval.

The complexity of cross-company collaborative, multi-drug IRPs poses both enormous opportunities and challenges for regulatory assessment. On the one hand, IRPs offer the possibility for patients and broader society to receive the best available treatment for their specific needs, in line with the latest advancements in biopharmaceutical R&D. On the other hand, however, the concept of IRPs is relatively new in clinical development and regulators have only recently started to develop recommendations to challenges such as the safety oversight of the trials, data transparency and integrity, how to control type I errors and more.

Conscious of these challenges, the EU-PEARL consortium places regulatory endorsement as a key aspect for the successful and effective uptake of any IRP. EU-PEARL plans to engage with representatives of European Medicines Agency (EMA), EU national Health Authorities (HAs) and the U.S. Food and Drug Administration (FDA), to assess their latest guidance on the role of IRPs in the regulatory evaluation and approval of new medicinal products. An External Advisory Board is to be established with representatives from HAs, ethics committees’ experts and EMA representatives to receive their advice as the project is implemented. Furthermore, EU-PEARL counts on a dedicated EMA Liaison Officer assigned to EU PEARL to guide navigation of the applicable EU regulations and processes.

Dialogue with the FDA is to be maintained and encouraged, following initial discussions with FDA representatives during the proposal configuration phase, and the FDA’s willingness to engage with EU-PEARL from the outset. Paul Ehrlich-Institute (EPI) one of the German HAs for approval of clinical trials and marketing authorisation applications is a partner in EU-PEARL. Engagement with HTA bodies is envisaged through the participation of EUROSCAN as project partner. EUROSCAN is an International Information Network on HTAs, which embraces 11 European HTA Associations. Additionally, EUROSCAN will bring in the contribution of HTAi, the International Association of HTA bodies. HTAi will be involved in EU-PEARL as Third Party of EUROSCAN.

Regulatory feedback is to be obtained in two workshops in cooperation with disease-related WPs and other relevant stakeholders and potentially by a request for an EMA Qualification Procedure to qualify methods proposed for IRPs.