EU-PEARL is a strategic partnership between the public and private sectors to shape the future of clinical trials. This innovative and challenging enterprise aims to create a tested and trusted framework for patient-centric integrated research platform (IRP) trials, through which novel techniques and treatments developed by multiple companies and organizations are tested in a platform trial.
To achieve this objective, EU-PEARL promotes cooperation amongst pharmaceutical companies, clinicians, patients and researchers and encourages knowledge sharing and open discussion amongst all stakeholders, including regulators.
This sustainable and reusable systematic approach to platform trials conceived to test multi-sourced compounds, is to be supported by a management structure designed by EU-PEARL which will be able to meet complex regulatory, ethical, legal, statistical and data requirements.
EU-PEARL is also developing the specific IRPs frameworks for platform trials ready to operate in four disease areas still facing high unmet needs:
Public and private alliances have formed around these four disease areas and are now ready to support innovative clinical drug research of new techniques and treatments. EU-PEARL is set to create trial-ready clinical networks in these four disease areas, so that platform trials can be initiated shortly after the project is completed and funding secured.
This project is funded by the Innovative Medicines Initiative (IMI), a large, far-reaching public-private partnership integrated by the European Union and the pharmaceutical industry to support research and innovation in life-science.
EU-PEARL aims to improve health outcomes for patients by shaping the clinical trials of the future. To achieve this vision, we have joined forces to create a sustainable and replicable framework that will produce a systematic approach to patient-centric, cross-company, multi-compound trial platforms.
EU-PEARL has set itself four objectives:
They are the backbone of the project as they will become the main beneficiaries of the Integrated Research Platform Trials that EU-PEARL promotes. Creating structured, systematic and sustainable patient engagement procedures on trial design and clinical R&D is a core objective to the project which the European Patient’s Forum (EPF) is contributing to develop.
This network lead by centers associated to the European University Hospital Alliance (EUHA) provides an experienced environment to carry out platform trials. It also facilitates an ideal space to foster the interactions with patients and all stakeholders.
The sound framework EU-PEARL is building will be based on an integrated set of statistical methods, tools and standardised procedures. Once it is fully developed, it will accommodate the evaluation of multiple treatments, whilst producing statistically valid results. Ultimately, this operational framework will serve a wider community, beyond the scope of EU-PEARL.
Data sources, their integration and the quality of pre-existing Electronic Health Records (EHRs) and future research and patient data conforms a fourth pillar of this project. EU-PEARL it is set to build robust policies for access to global data and the creation of a governance structure that promotes transparency, engagement and utilisation for optimal future sustainability of the platform.
All stakeholders within the project are engaged in the alignment of their objectives to comply with European and national data protection & ethical regulations and legislation with a view to obtaining regulatory endorsement of IRPs.
EU-PEARL has adopted a governance model that promotes the active participation of all involved stakeholders, including both academia and EFPIA partners as well as other interested parties such as pharmaceutical companies, patient groups, regulators, CROs, etc. in order to achieve maximum collaboration. The management structure of EU-PEARL has been developed to respond to the needs of an international large-scale multi-stakeholder project. It is based on traditional management structure adapted to the particular attributes of EU-PEARL.
EU-PEARL is a challenging project to manage due to its size, its ambition, the variety of activities and their interdependencies. The project aims to harmonise the interests of the public and EFPIA partners, therefore a strong internal trust and communication interface is crucial to setting the project up for success.
VHIR acts as EU-PEARL Coordinator and Janssen as Project Leader. They play a central role in driving the project strategy and chairing the governance bodies.
Taking into account these project characteristics, EU-PEARL management structure is based on a multi-level organisational structure which includes:
Forum for discussion, dissemination and scientific community-building within the project.
The Forum consists of the project partners, third parties and the Associated Collaborators and has the purpose of stimulating discussion and promoting dialog on scientific issues.
The Forum does not have decision-making powers.
This plenary assembly has the ultimate decision-making responsibility in matters affecting the overall project strategy and composition of the consortium and all other matters that the Executive Committee (ExCom) opts to refer to a higher level. This includes approval and disapproval of amendments to the grant agreement, any significant deviations and changes in the consortium composition.
+ See more
The GA is regularly informed by the ExCom of the progress of the project, hosts scientific discussions and supervises the correct implementation of the governance structure.
Several members of each organization can participate in the GA (but only one vote per institution is allowed). The GA meets twice per year.
The ExCom is the primary decision‐making body, responsible for the determination of project policies and the overall scientific leadership of the project as well as its strategic oversight. The ExCom is composed by the following partner organizations: VHIR, EATRIS, Janssen, Novartis and (non-voting) SYNAPSE.
+ See more
Using the necessary input from the Steering Committee (SCom), the ExCom follows up progress in the different WPs. It dynamically steers efforts, requires reports from the Project Management Office (PMO) and the SCom and intervenes as needed to solve conflicts.
In particular, the ExCom deals with amendments to the work plan and changes in budget allocation between WPs and approves those modifications of the work plan suggested by the SCom. It approves project deliverables, ensures that objectives and milestones are fulfilled with appropriate quality and decides on strategic roadmaps with regards to the project.
The ExCom may require specific actions or reports from the PMO and/or SCom in order to solve any issues that cannot be clarified or agreed at the operational level. These include mediating disputes and resolving matters relating to allocation of tasks and efforts, dealing with situations where underperformance is suspected, approving mitigation and contingency plans, and optimally handling situations in which the project efficiency might be endangered.
The ExCom is in constant communication and meets frequently by teleconference (at least bimonthly).
The Steering Committee (SCom) is formed by the Coordinator, the Project Leader and each of the Work Package Leaders (WPLs). It is responsible for ensuring alignment, scientific coherence and coordination across WPs.
The SCom is the leadership team responsible for the day-to-day coordination and oversight of the Work packages (WPs) activities and interdependencies.
+ See more
It is in charge of following up overall progress as reported by the WPs, dynamically steering efforts to ensure scientific alignment between them, requiring reports and following up progress in the different WPs and solving input‐output relationships among them intervening as needed to solve conflicts, and deciding on issues that should be referred to the ExCom.
For efficiency, the SCom can suggest minor work plan updates, overseeing multi stakeholder engagement and suggesting effort/budget reassignment within WPs in pursuit of optimal, global efficiency. These suggestions are elevated to the ExCom for their approval.
The SCom produces recommendations and preparatory materials needed for the ExCom and GA to decide efficiently. The SCom meets monthly.
The PMO is a support office and is operationalised by SYNAPSE.
SYNAPSE provides long-standing experience in managing complex Public-Private Partnerships including IMI projects (16 IMI Projects, among which EMIF, EHDEN and EPAD).
This PMO supports the ExCom and the SCom at the management and operational levels.
+ See more
It deals with:
The PMO is led by SYNAPSE and composed also by VHIR, Janssen, Novartis and EATRIS. It meets monthly but holds regular meetings, mostly by teleconference, to follow up on managerial matters.
This is a consultative body established to provide advice directly to the ExCom on specific areas related to the project. It is composed of senior experts external to the consortium (between 4-8 members) including a senior EMA representative. It includes ethics experts who advise on the ethical perspectives for patients that are raised by the IRP design elements proposed by the project. Senior experts from the CROs sector are also invited to be part of the EAB.
The EAB is invited to project meetings to review the project’s progress and delivery outcomes.
ACs are institutions and teams interested in supporting the project, but that do not become full partners and sign the Grant/Consortium Agreements.
This allows the project’s constituency to expand beyond the core consortium partners and to leverage third parties’ expertise, knowledge and connections with other relevant worldwide initiatives for the benefit of the project. All ACs sign a specific agreement and agree to basic engagement mechanisms. Most ACs have long-standing scientific relationships with core partners.
+ See more
One of the fundamental founding principles of EU-PEARL is to generate a critical mass of research capacity spanning all relevant stakeholders, in order to maximise its impact and create a long-lasting, far-reaching community effort in the field. In order to achieve this goal, EU-PEARL has been designed from the outset as an inclusive structure that encourages active participation of all members and in which their diverse perspectives can have proper exposure and consideration. At the same time, the Consortium needs to be manageable in order to not endanger the ambitious, pragmatic scientific goals of the project.
The solution for this trade-off, inspired by the successful experience acquired in other IMI projects (ADVANCE, RESCEU) is the Associated Collaborators (ACs) role.
The ACs are part of the EU-PEARL Forum and are informed and updated on project activities and invited to participate in discussions and work related to the project. ACs contribute to the project participating in the deliberations of the consortium, engaging with core partners on specific tasks, as required, while respecting:
It is expected that they explore the options to make trial unit(s) ready for the platform and the adaptive trial ready so that the built network can start running trials at the end of the project.
To transform the current siloed approach to clinical trials into a collaborative IRP-based paradigm, a lasting culture shift is required throughout the entire ecosystem of stakeholders. The EU-PEARL consortium reflects the key players in this ecosystem and brings together:
· regulators, through the links that will be established with EMA, and the participation of the regulatory body PEI
· patients, through the pan-European patient advocacy group EPF which represents 67 organisations and an estimated 150 million patients
· healthcare providers (VHIR, EMC, Charité, APHP, USR, LMU, KU Leuven)
· a university hospital (KU Leuven)
· academic institutions (UOXF, MUW, UNEW, KCL, USR, UMIL, KU Leuven, LMU, UoM)
· research centres (EATRIS, VHIR, IHD, ECRIN),
· a Health Technology Assessment body (EUROSCAN),
· small and medium-sized enterprises (SMEs) (BERRY, CUSTODIX, SYNAPSE, DocuMental),
· EFPIA partners (Janssen, Novartis, Sanofi, Pfizer, Servier, Allergan, AZ, Novo Nordisk, Otsuka, Teva), and
· IMI Associated Partners (CTF, TB Alliance, SpringWorks).
The project is shaped through involvement of renowned research centres, IMI partners and subject matter experts in design and execution of research platforms.
The consortium is well equipped to tackle the complexity of this transformation based on its internationally recognised and complementary expertise with a broad span across Europe; the bandwidth to leverage and maximise synergies with existing related initiatives and projects; and the extensive experience in collaborating in large public-private partnerships with a variety of stakeholders.Get to know all Partners
This work package focuses on the quality, governance and long-term sustainability of the IRP solution. WP1 will ensure the overall sustainability of the project and make sure that the outcomes can be used beyond termination of EU-PEARL. Its main tasks include the outline of a legal framework in compliance with GDPR regulations, involvement of patient engagement platform and evolving Data Management plans, IRP business plans and setting quality standards for IRPs.
WP2 centers in establishing the statistical and methodological side of the IRP solution(s) by covering regulatory, ethics, statistical and operational aspects. This work package identifies current best practices and standardization of the IRP and develops statistical methods for trial designs and analysis. Regulatory frameworks for IRPs are being evaluated and developed in accordance to EU-PEARL specific requirements, which are then being assessed by ethic committees. WP2 is also focused in providing the necessary tools for the implementation of platform trials.
WP3 is responsible for identifying the common requirements for Clinical networks from all disease specific areas to develop a best-case scenario on what kind of network might be applicable for EU-PEARL. Existing clinical data network IT infrastructures in IRPs are being leveraged and extended to support the development of a suitable tool for EU-PEARL. Different existing IT solutions are being evaluated and a blueprint that integrates clinical investigator and patient data network resources for conducting IRPs is being developed. This work package will not develop a specific tool but instead will outline the clinical and patient network requirements.
WP4 is working on a reusable and modular approach for the design and execution of IRPs in treatment resistant depression (TRD) and partially responsive MDD (PRD), focussing mainly on an early life development (Proof of Concept POC/Phase II). To achieve this goal, WP4 is outlining scientific challenges and the digital phenotypes for TRD and PRD. A protocol on the Longitudinal Natural History Study in both MDD types will help provide feedback to WP2 and WP3 on key requirements for IRPs in PRD and TRD.
WP5 focuses on developing the framework for a clinical trial platform that allows accelerated progression of TB compounds through phase II and III studies. This work package sets a special interest on composing novel regimens that suit the requirements for high-burden and low-resource countries. WP4 works closely with regulators and discusses regulatory pathways for the novel approach. A crucial part are the patient cohorts, registries and EHRs and the evaluation of whether the capacity to perform platform trials is feasible across the relevant regions. A compilation of selected criteria to qualify drugs and drug combinations to enter platform studies should be available as part of the IRP approach in TB. WP5 works closely with WP1, WP2 and WP3.
As of yet, there is no effective treatment available for patients suffering from NASH. WP6 is defining the scientific challenges of the illness in the context of IRPs and will formalise the requirements and infrastructure needed to operationalise a NASH IRP. This approach involves obtaining input from regulatory, ethics, scientific and patient organisations and therefore requires a strong liaison with WP1-WP3.
WP7 is defining the current challenges that a design of an IRP for NF1 and NF2 can face taking into account the disease progression, the identification of biomarkers and available treatments and patient recruitment. A protocol for a broad longitudinal natural history study is being developed as a base to create the infrastructure that is needed to operationalise an IRP for Neurofibromatosis.
WP8 provides management support and is responsible for the overall monitoring on tasks and interdependencies. For that purpose, a project plan is in place which also outlines possible risks that may arise during the project and mitigation strategies. This work package also engages in the reporting and the timely delivery of deliverables and milestones. Internal and external communication strategies have been laid out, whilst possible alliances with other ongoing initiatives are explored.