Part 1: The EU Context
Unmet needs of rare diseases and the status quo of European research
ERNs and the potential they offer
The concept and origins of ERNs
ERNs and research
“(5) To fulfil the requirement set out in point (iv) of Article 12(4)(a) of Directive 2011/24/EU (‘make a contribution to research’), the Networks must: (a) identify and fill research gaps; (b) promote collaborative research within the Network; (c) reinforce research and epidemiological surveillance, through setting up of shared registries”
ERNs are permanent infrastructures
ERNs sit at the interface of the research and clinical spheres
ERNs are designed to ensure comprehensive disease (and specialised procedure) coverage
Data generation/linkage and digital health opportunities
Part 2: Understanding constraints on ERN Research to-date: and in particular, barriers to Industry collaboration
What factors have limited ERN-led research?
Contrasting priorities in the early years of ERNs
Lack of suitable funding
Some ERNs represent communities with a limited research track record
Confusion in defining research activity ‘of an ERN’
Barriers to ERNs and Industry Collaboration
“ERNs are still on a learning curve in terms of collaboration and so engagement with all stakeholders to explain the value of collaboration is important” (Franz Schaefer, Coordinator of ERK-NeT, the ERN for Rare Kidney Diseases).
The scope and significance of the statements from the ERN board of member states
Conflict of Interest
Privacy and ethical concerns
The lack of legal status for ERNs
Lack of experience in the legal and bureaucratic processes involved in working with Industry
Part 3: Methodology and the Added-Value of Together4RD
How Together4RD is fostering ERN-Industry collaboration
Possible frameworks to guide ERN-industry collaboration
Learning from case studies: extrapolating lessons and good practices for ERNs and industry
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Firstly the different sorts of collaborations possible with Industry;
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on the ‘Registries’ side, these include accessing registry data to elucidate natural history, to conduct post-marketing surveillance, to serve regulatory purposes as Real-World Evidence (RWE), and collaborating on the definition of datasets.
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In terms of broader ‘Clinical Research’, activities ranged from strategic fora to advance research to creating opportunities for researchers to pitch ideas to companies: and from creating or improving biobanks to diagnosing patients through electronic health records.
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And Secondly, to match examples of each activity to achievements of the different case studies, to show how some of these Industry collaborations have been approached to-date.
Towards Together4RD pilots
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dedicated discussions exploring the types of activities which have been conducted to-date between networks (typically predating ERNs) and other groups of stakeholders, on the one hand, and Industry on the other (see above, ‘Learning from Case Studies’)
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extrapolating what such activities would look like under an ERN setting, specifically—what good practices could be embedded (and what resources could be leveraged, thinking of data access agreements etc.) and what would need to be avoided, to deliver the activity ethically and effectively
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Seeking input from the Together4RD Industry sponsors and from all ERNs (via communications issued by the Chair of the ERN Coordinators’ Group) on potential pilots that could be implemented in 2022/23
Clarity of goals and expected outcomes | Potential for scaling up to other ERNs |
If there is already an established infrastructure in place | Proposal has patient group support, specifically from the patient group involved in the ERN or ERNs that would participate in the pilot |
Resources available/ committed | Involvement of smaller ERNs |
Single to multiple company pilot | Has potential to satisfy BoMS criteria |
“It is important that pilot activities exploring ERN and Industry collaborations are able to provide added-value for ALL ERNs in some way, and do not solely focus on fields which are already reasonably mature, research-wise”
A pilot for all ERNs
Part 4: Conclusions, recommendations, and policy asks
“Clear rules are required that enable European Reference Networks to collaborate with industry across a range of pre-agreed activities, clarified and tested through pilots, using shared SOPs to accelerate research and build mutually-agreeable public private partnerships: a central business development/tech transfer office could promote, coordinate and supervise European Reference Networks interactions and agreements with industrial partners” [7]
Barrier to ERN-industry collaboration | Solutions in development by Together4RD (or others, as appropriate) |
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Concerns on the part of some members of the ERN BoMS concerning Industry and ERN interactions: stemming from a lack of awareness of the nature such collaborations can take, and of the current extent of successful collaborations outside of the ERNs | Development of rare disease case studies to illustrate a range of examples in which networks (at national and international level) engage/have engaged with Companies for particular purposes |
Disseminating these case studies to the BoMS, to show that win:win collaborations indeed exist | |
Concerns from the BoMS (and indeed from ERNs and patients themselves) over conflicts of interest | Initiating ERN-Industry engagement via Together4RD pilots, using the Code of Conflict developed by the WG on Legal and Ethical Issues, should appease concerns |
Possible lack of awareness or clarity on the range of activities which could take place between ERNs and Industry | Utilising the case studies to more clearly distil the sorts of activities which could feasibly occur between ERNs (specifically, moving forwards) and Industry, to support the development of palatable pilot proposals the BoMS members would support |
Concerns amongst BoMS that opening the door to ERN and Industry interactions would only benefit a few of the already more research mature ERNs | Together4RD will explore launching a multistakeholder forum to enable ERN and Industry interactions and advance strategic (and increasingly operational) collaborations across the board. Together4RD will, with the stakeholders involved, agree a preferred model for this |
Administrative and bureaucratic efforts and time required to contract with Companies (exacerbated in the absence of a readily-available legal entity) | Planned development of standardised templates all ERNs could use (by making use of a designated HCP or Third Party) to contact with single Companies or multiple Companies |
The fact that ERNs are not legal entities, and it appears that the European Commission is not seeking to make them so (in the near future at least) | The pilots showcased by Together4RD will demonstrate how either a consortium model or third party agreement may serve to deliver the results ERNs and Companies wish to see. It may be concluded that different Frameworks suit different sorts of activity, but either way, guidance -for now and for the future- will be proposed by Together4RD in the light of the pilot experiences |
Inadequate funding for ERNs limits scope and ambition to engage in research in a meaningful way | Under the EU4Health programme, greater financial resources (provided through more amenable and appropriate and less bureaucratic grant processes) is already relieving pressure on the ERN coordination teams, which should serve to stabilise the core Network structures and services. Additional public funding is expected from the future RD Partnership and eventually from Member States to support ERN research activities and data collection. Coupled with a means of obtaining private funding for mutually-beneficial research activities, accelerated by Together4RD, and bolstered by a robust Code of Conduct issued by the Working Group on Ethics and Legal Issues, the hope is that resourcing becomes less of a barrier to ERNs fulfilling their potential |
Lack of certainty on the part of ERNs of what they are able to do with Companies, and how to approach different activities | The disease-related pilots selected to be showcased by Together4RD will be closely followed and analysed, to distil good practices and lessons learned, which should serve to optimise all future interactions and should be illuminating for less-experienced Networks |
ERNs and their potential are not always well understood—some companies, especially SMEs with limited European traction, are not aware of their existence or if they are, do not realise the breadth and depth of expertise ERNs offer | This Position Statement in itself should begin to raise awareness amongst the broader private sector. Foreseeably the Moonshot (and future RD Partnership, if Industry is able to eventually play a meaningful role) will also serve to boost this awareness-raising. The Together4RD pilot on a forum/fora by which ERNs and Industry can connect transparently and discuss needs and strategies with patients and other key stakeholders, should also address this challenge. And as Together4RD pilots are delivered, presumably increasingly word will spread of the ERNs in SME circles even outside of Europe |
Limited basic research and Industry interest in the conditions addressed by a given ERN, which traditionally has therefore had limited research activity | Together4RD will offer benefits here firstly by simply networking the various stakeholder groups involved, and opening up the conversation. A pilot providing either a cross-ERN forum for strategic Industry discussion, or ERN-specific multistakeholder fora, will create a space for all ERNs and thus all disease domains to identify research gaps and meaningful patient-centred needs, and foreseeably make it easier to devise projects to begin to address these and build momentum for neglected conditions (which potentially could be supported through the future RD Partnership, Moonshot or other avenue) |
Conclusions and recommendations on moving from past case studies to ERN-industry projects
Unlocking the potential of data
“ERNs are the cornerstone of clinical research on rare diseases. EURORDIS and the patient community call to establish ERN-industry collaborations under a public-private partnership framework informed by flagship pilots, to harness the research capacities of all partners, making Europe more competitive globally”
Managing stakeholder expectations, building trust and consolidating partnerships
Open and transparent engagement between ERNs and industry
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it works against the very spirit of open and transparent interaction sought by the companies, the ERNs and the patients and of course the BoMS itself, and actually creates more grey areas;
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it prevents Industry and ERNs from embarking on truly new activities. The sorts of collaborations summarised in part 3 have, in most cases, been happening for years—but truly new activities are foreseen which the ERNs are perfectly placed to usher in with Industry. Whereas it may be possible for individual ERN experts or HCPs to continue their ‘business as usual’ collaborations, it is likely that few would feel comfortable embarking on new and substantial projects with Industry which would very clearly be seen as activities OF the ERN, in the absence of a supportive atmosphere such as Together4RD is seeking to provide;
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it perpetuates the differences—and potentially inequalities- in experience between ERNs, as those with robust research communities continue to engage in their own capacities, if not exactly as the ERN, whilst the ERNs representing fields with limited or no research activity will surely struggle to open up opportunities and overcome the relative inertia in a climate in which Industry engagement is somehow frowned upon.
Leveraging strategic and political opportunities
Recommendation 1: ERN Governance | Recommendation 2: Public–Private Research Collaboration |
Promote transparent governance structures and open dialogue to empower and advance ERN—industry collaboration | Create a Forum (or Fora) for public–private exchange of pre-clinical knowledge for ERNs |
Recommendation 3: Independent, Well Resourced and Effective ERN Registries | Recommendation 4: EU Rare Disease Action Plan Collaboration |
Ensure ERN registries are adequately financed via public funds and remain independent, whilst clarifying & optimising their potential for collaboration | Create a comprehensive European Action Plan for Rare Diseases that supports public–private partnerships |