Transnational research proposals must cover at least one of the following areas, which are equal in relevance for this call:
- Research to accelerate diagnosis, e.g:
- New schemes for finding diagnosis for undiagnosed patients;
- Improved annotation and interpretation of variants and development of diagnostic tests for the more prevalent variants;
- Novel modalities of functional analysis of candidate variants through in vitro, cell, tissue or animal studies.
- -omic or multi-omic integrated approaches for discovery of disease causes and mechanisms including development of relevant bioinformatic tools;
- Research to explore disease progression and mechanisms, e.g:
- Natural history studies and patient registries (also for clinical trial readiness). Whenever possible these should include development and use of patient reported outcome measures. In addition, the exploration of the use of standardized M-Health-based surveillance instruments and of patient entered data to gather information for natural history studies is welcome;
- Identification of clinical biomarkers, clinical outcome measures and surrogate endpoints;
- Identification of novel pathophysiological pathways in appropriate disease models that effectively mimic the human condition.
Furthermore, additional elements need to be considered in the application:
- The design of the study (sample collection, statistical power, interpretation, relevant models for hypothesis validation) must be well justified and has to be part of the proposal;
- For natural history studies and patient registries: strategies and timelines for patient recruitment, retention, assessment, and analysis must be included. Data supporting the proposed recruitment numbers is mandatory. The study design and objectives should take into consideration what information regarding the rare disease population would be needed in order to pursue clinical trials or other health care related studies in that rare disease. There always need to be clear research questions that are addressed in the study/registry. Clear plans for sustainability of the resources must be described. Consideration of common data elements as outlined in the recent publication “Set of Common Data Elements for RD Registration” (http://www.erare.eu/sites/default/files/SetCommonData-EU%20RD%20Platform_CDS%20_final.pdf) is highly recommended;
- Appropriate bioinformatics and statistical skills should constitute, whenever justified, an integral part of the proposal, and the relevant personnel should be clearly specified;
- The new research data resulting from the project should be treated permissible according to the FAIR principles, and deposited and shared, according to the national/regional rules of the countries involved. It is strongly advised to make data accessible through RD-Connect (http://rd-connect.eu/ – connecting databases, patient registries, biobanks and clinical bioinformatics data into a central resource for researchers worldwide) and through Elixir (https://www.elixir-europe.org/platforms/data/elixir-deposition-databases – compiling a list of resources for the deposition of experimental, biomolecular data). To make research data findable, accessible, interoperable and re-usable (FAIR), a data management strategy for the proposed full project is mandatory in the full proposal stage. Some countries involved in EJP RD JTC 2019 will also ask for a data management plan (DMP) at national level at the stage of full proposal or after granting of the project.
- To ensure that the needs and priorities of rare disease patients are adequately addressed, they or their representatives should be appropriately involved in all projects wherever relevant. For examples, inclusion and involvement of patient representatives includes but is not restricted to natural history studies / registries where patients should be involved in the governance of the registry. Please consult the INVOLVE website for information on various ways to involve patients: http://www.invo.org.uk/resource-centre/resource-for-researchers/. For additional guidance and practical advice on patient involvement in research studies, please consult also the JPND guidelines: http://www.neurodegenerationresearch.eu/wp-content/uploads/2013/11/JPND-guide-for-Patient-and-Public-Involvement.pdf .
The following approaches and topics are excluded from the scope of this call:
- Approaches concerning rare infectious diseases or rare cancers;
- Approaches concerning rare adverse drug events/medical complications in treatments of common diseases;
- Studies that focus on pre-clinical therapy development and/or validation in cellular or animal models. These will be addressed in future calls;
- Interventional clinical trials;
- Rare neurodegenerative diseases which are within the main focus of the Joint Programming Initiative on Neurodegenerative Disease Research (JPND; http://www.neurodegenerationresearch.eu/). These concern: Alzheimer’s disease and other dementias; Parkinson’s disease (PD) and PD-related disorders; Prion disease; Motor Neuron Diseases; Huntington’s disease; Spinal Muscular Atrophy and dominant forms of Spinocerebellar Ataxia. Interested researchers should refer to the relevant JPND calls. Not excluded through this specification are childhood dementias/neurodegenerative diseases.
Projects shall involve a group of rare diseases or a single rare disease following the European definition i.e. a disease affecting not more than five in 10.000 persons in the European Community, EC associated states and Canada. Applicants are encouraged to assemble groups of rare diseases based on solid criteria and commonalities if this leverages added value in sharing resources or expertise and has the capacity to elucidate common disease mechanisms and therapeutic targets.
The research projects submitted within this call must be based on novel ideas stemming from consolidated previous results or preliminary data and must be clearly endowed with benefit for the patients, i.e. studies allowing a rapid implementation into public health-related decisions or into the clinics. To achieve this goal, the necessary expertise and resources should be brought together from academia, clinical/public health sector and private companies whenever relevant. The research teams within a consortium should include investigators from complementary scientific disciplines, research areas and expertise necessary to achieve the proposed objectives.
The research proposals must demonstrate complementary and synergistic interaction among the partner teams. There should be clear added value in the transnational collaboration over the individual projects, in terms of:
- Gathering a critical mass of subjects/patients and or subjects/patients databases and corresponding biological materials that would not be possible otherwise;
- Sharing of resources (biobanks, models, databases, diagnostic tools, etc.), of specific know-how and/or innovative technologies including “-omics”, and of expertise. The projects should clearly demonstrate the potential health impact.
 FAIR: Findable, Accessible, Interoperable, Reusable (for more information: see “The FAIR Guiding Principles for scientific data management and stewardship” (https://www.nature.com/articles/sdata201618)