The Trials4Health call has the aim to support randomised, interventional multi-country Investigator-Initiated Clinical Studies that are designed as pragmatic comparative-effectiveness studies and/or drug repurposing studies, and to encourage and enable transnational collaboration between clinical and public health research teams that conduct multi-country IICS, either comparative-effectiveness or drug repurposing studies.
Proposals should take into account the following points that apply according to the selected clinical trial design:
1)The proposed study needs to be a pragmatic comparative effectiveness trial and/or a drug repurposing trial, designed as Phase III randomised interventional trial. The clinical design should be appropriate and justified. Cluster randomisation could be considered in the clinical trial design if justified.
2) In case of comparative effectiveness trials, these must compare the use of currently approved or existing healthcare interventions (see definition), used in clinical practice in Europe, either to each other or to the current standard of care.
3) In case of comparative effectiveness trials, these must consider existing, approved healthcare interventions (see definition) which could include but would not be limited to: diagnostic, screening, prevention and treatment interventions. The interventions can be pharmacological as well as non-pharmacological procedures like well-defined, reproducible and targeted nutritional and lifestyle interventions, surgery, prognosis methods, use of medical devices, nano and advanced health technologies, eHealth and digital interventions and other health interventions.
4) In case of drug repurposing trials, the aim shall be to explore a new indication of an approved off-patent medication. Given that this call is supported by public funding, clinical studies with a commercial purpose are excluded, therefore only off-patent drug repurposing trials are allowed.
5) These interventions shall have high public relevance in at least one of these specific diseases or conditions (that are of equal importance):
- Cardiovascular diseases
- Metabolic disorders
- Autoimmune diseases (including antibody-based autoimmune diseases and/or also other Immune-mediated inflammatory diseases)
The focus of the multi-country Investigator-Initiated Clinical Studies is cardiovascular, metabolic or autoimmune disorders as primary causes of illness. Proposals may focus on a single cardiovascular, metabolic or autoimmune disease, or they may explore these conditions in combination with comorbidities.
Beyond the research topics, several following requirements and recommendations as well as the Out of scope conditions should be considered by applicants, including approaches to Responsible Research and Innovation (RRI) (please consult the Call text document and the Guidelines for applicants document for further information, including the RRI guidelines and specific national/regional restrictions).
Submission:
The submission and evaluation procedure will be in two-steps for joint applications. The second step of the evaluation process will include a rebuttal stage and an interview with the coordinating investigator and the representative of the sponsor. For both steps, proposals (in English) shall be prepared by the consortium partners following the ERA4Health template (included in the ERA4Health website) and must be submitted by the coordinator via the electronic submission system tool Pt-outline (LINK).
Eligibility criteria:
Applicants must demonstrate that the research teams contains the necessary breadth and depth of expertise in all methodological areas required to deliver the proposed study.
Principal Investigators should demonstrate experience and expertise in the conduct and delivery of clinical trials.
Size of the consortium:
The number of participants and their research contribution should be appropriate for the aims of IICS and be reasonably balanced in terms of international participation. Each IICS should represent the critical mass to achieve ambitious scientific goals and should clearly demonstrate an added value from working together.
The project must be a transnational project involving eligible research partners from a minimum of 3 (three) and a maximum of 5 (five) different countries participating in the call. In addition, in each consortium at least two eligible partners (independent legal entities) must be from different EU Member States or Horizon Europe Associated Countries participating in the call.
A maximum of 3 (three) collaborators per consortium is allowed. Collaborators are self-funded partners. Please check the call text for further conditions that apply to the composition of consortia and for collaborators.
Each study consortium must nominate a clinical study coordinator among its partners (NOT a collaborator). The clinical study coordinator cannot be a commercial enterprise or for-profit organisation.
Each Principal Investigator can submit only 1 (one) pre-proposal as coordinator or as simple partner (i.e. the coordinator or the partner of a proposal cannot be a partner in another proposal).
Financial and legal modalities:
Each clinical study partner will be funded by its relevant national/regional funding organisation. Therefore, eligible costs, funding rules and other specific aspects allowed may vary between the respective funding organisations (see Annex I). Due to these differences, it is recommended that each clinical study partner defines its own budget in accordance with the funding rules of its own country/region.
For information on the specific funding rules and eligibility criteria of the national/regional funding organization, please carefully read Annex I and the national/regional announcements of the call and the guidelines for applicants.
Applicants are consequently strongly encouraged to contact their national/regional contact points to check their national/regional eligibility rules before submission (see Annex I in the call text). Please note in some countries/regions this may be mandatory.
With the respect of the specific conditions detailed in the call text and the guidelines for applicants, an additional budget of a maximum up to 15% of the total budget requested to the national/regional funders can be requested for covering the conduction of cross-cutting management activities (i.e. clinical study management activities at consortium level) such as trial authorizations, drug, safety and data management under the responsibility of thecoordinating investigator and his/her legal entity through collaboration with ECRIN (www.ecrin.org). See call text document and guidelines for applicants ("Funding mechanism" section for further information and specific deadlines).
Please note that if a partner is found to be non-eligible at any step of the process by one of the funding organisations, the entire proposal could be rejected without further review. Therefore, please make sure to carefully read and follow the respective national/regional regulations in Annex I.
Formal check and evaluation of pre-proposal
After submission, the JCS will check all pre-proposals to ensure that they meet the call’s formal criteria (date of submission; number of participating countries; inclusion of all necessary information in English; appropriate limits on length). In parallel, the JCS will give access to the pre-proposals to the national/regional funding organisations, which will perform an administrative check for compliance with national/regional regulations.
The pre-proposal of each consortium passing the eligibility check (JCS and country/region) will be evaluated by external reviewers. Evaluation of a pre-proposal will be made by three reviewers with a scientific/clinical background. One of these three reviewers will have specific expertise in clinical trial methodology and biostatistics. Potential conflicts of interests of the evaluators will be taken into consideration during the allocation of the proposals. The reviewers will perform the assessment of the pre-proposals and complete a written evaluation form with scores and comments for the evaluation criteria that they should evaluate. The evaluation will include an eligibility check that the proposal is included in the call scope (e.g. disease area, type of trial, etc). Based on the scores in the written evaluations, a ranking list will be established.
The Clinical Study Steering Committee (CLSC) members will meet to decide which proposals will be invited to submit a full proposal based on the reviewers’ recommendations and to ensure a reasonable balance of requested and available national/regional budgets. Pre-proposals which do not pass this assessment will not be invited for the full proposal stage. All consortia will receive the full evaluation reports, excluding the evaluation scores.
Formal check and evaluation of full-proposal
After submission, the JCS will check the full proposals to ensure that they meet the call’s formal criteria and have not changed substantially from the respective pre-proposals before sending them to the reviewers.
Each full proposal will be allocated to three reviewers with a scientific/clinical background and taking into consideration the potential conflicts of interest between the reviewers and the applicants. One of these three reviewers will have specific expertise in clinical trial methodology and biostatistics. The reviewers will perform the assessment of the full proposal and complete a written evaluation form with scores and comments for each criterion (see evaluation criteria below).
Additionally, a Patient Advocacy Committee will assess the patient involvement and relevance for patient needs in the full proposals and will complete a written review.
Each coordinator is provided with the opportunity of getting acquainted with the assessments and commenting on the arguments and evaluations of the reviewers (see section “Rebuttal”) before the Peer Review Panel (PRP) members meet to discuss each full proposal in a PRP meeting.
In addition, an online interview of the coordinator and the person responsible for the implementation of clinical studies in the sponsor organisation, according to the organisation's legal structure, authorised to speak on behalf of the sponsor and identified by the consortia in the full proposal, will take place. This interview will evaluate the capacity of the sponsor and the coordinator to implement the clinical study. Apart from the coordinator and the representative of the sponsor, a maximum of three other additional representatives of the research consortium can attend this online interview, in case that their specific expertise is needed to demonstrate the capacity to implement the clinical study (e.g. biostatistician of the research consortium).
During the PRP meeting, the reviewers and interviewers will discuss all proposals and produce a ranking list of proposals recommended for funding. Representatives of the Patient Advocacy Committee will be invited to take part in the discussion and present their assessment of the patient involvement of each proposal during the PRP meeting. They will have voting rights similar to the scientific evaluators attending the PRP, in case that a voting procedure is needed to take the final decision.
Evaluation criteria
Proposals not relevant to the call topic and objectives (out of the scope) will be declared ineligible and will not be funded and forwarded to full proposal stage independently of their scientific quality.
Pre-proposal
1.Excellence
2.Impact
3.Quality and efficiency of the implementation
Full proposal
1.Excellence
2.Impact
3.Quality and efficiency of the implementation
4.Competence of the research team and quality of research environment
5.Methods and Design of the clinical trial
The specific evaluation criteria for pre-proposal and full proposal evaluation can be found detailed in the call text document. A consortium will not be funded if the sponsor does not present the capacity to implement a transnational clinical study, independently of the scientific quality of its proposal.
Scoring system
Evaluation scores will be awarded for each main criterion. Each criterion will be scored out of five. The weight of each main criterion is equal. Only integer values are accepted. The maximum scoring for pre-proposals will be 15 points and for full proposals 25 points. Full proposal will be considered fundable if the threshold average score for individual criterion is 3 points and the overall score is at least 17 points.
Rebuttal stage
Before the PRP members meet to discuss the full proposals in a PRP meeting, each coordinator is provided with the complete reviewers’ assessments. This stage allows applicants to comment on factual errors or misunderstandings that may have occurred in the review process and to reply to reviewers’ questions. However, issues not related to reviewers’ comments or questions cannot be addressed and the work plan cannot be modified at this stage.
The applicants will have up to 12 calendar days (24th August to 4th September, 2026) for this optional response to the reviewers’ comments. Answers sent after the notified deadline, or not related with reviewers’ comments or questions will be disregarded.
Interview of the coordinating investigator and the representative of the sponsor
The coordinating investigator and the representative of the sponsor will be jointly interviewed by an interview committee (formed by 3 experts that will be part of the PRP) to determine the capacity of the coordinator to implement the proposed clinical study and of the sponsor to oversee and manage it. The JCS will attend the interviews as observers. During the interview, a qualitative assessment of the feasibility of the trial will be performed. All PRP members will receive the feedback of the interview committee (which will be a qualitative gradual assessment of the feasibility of the study) which will be considered during the PRP discussion in the PRP meeting.
PRP meeting
The JCS will give the PRP members access to all full proposals, reviews and rebuttals, outcomes of the interview of the coordinators and sponsors, avoiding any conflicts of interest. The PRP will meet to discuss each proposal and, after consideration of the evaluation criteria, external reviews (patient representatives), rebuttals, interview outcomes, their own reviews and discussions, the PRP will assign final scores, make a classification of the proposals, and rank proposals recommended for funding. The final summary review report prepared by the PRP members will be sent to the respective coordinating investigators.
Ethical clearance
After the PRP meeting, ethics experts will remotely check the full proposals, which are recommended for funding by the PRP and selected for funding by the CLSC, for alignment with ethical norms and regulations . A meeting will also be organised for a discussion between the different ethics experts, if necessary. The ethics experts may ask the consortium for clarifications on the ethical points related to the proposed research approaches. The Ethics experts may highlight some vigilance points that need to be monitored during the implementation of the funded clinical study. Only those proposals approved by both the scientific evaluation and ethical assessment (complying with all central Horizon Europe and regional/national ethical requirements), will be funded.
Clinical study selection and reconfiguration process
A first selection of the clinical studies for funding identified as the main list will be made by the national/regional funding organisations based on the ranking list established by the PRP, available funding and the ethical clearance outcomes. After the establishment of the main list, additional clinical studies that have been assessed to be of good quality by the evaluation process could be invited to restructure their consortia, if there is any remaining funding budget. Research consortia will be provided 15 calendar days for this reconfiguration process. Restructuring may take place, taking into account the boundary conditions that are specified in the call text. Further details can be found in the call text.
Coordinating investigators having submitted an eligible proposal will be informed about the funding recommendation regarding their proposal by the JCS. Coordinating investigators are responsible to communicate this information to their clinical study partners. ERA4Health will publish in its website the information regarding the co-funded projects by the call, once that the call procedure has completely finalised.
Redress procedure
Applicants can appeal against the evaluation outcome if they suspect a breach in the application of the evaluation and selection procedures. This redress procedure only covers the procedural aspects of the evaluation and/or central formal eligibility checks.
Requests for redress on national/regional eligibility decisions will not be handled by the JCS and need to be addressed to the responsible national contact point. A mere disagreement with peer reviewers or panel members’ comments are not grounds for an appeal. The redress procedure will not call into question the scientific or technical judgement of appropriately qualified experts.
In this case the applicants shall submit their appeal to the JCS via email (Trials4Health@isciii.es) up to 7 calendar days after the date of the eligibility check or evaluation outcome email notifications by the call secretariat at the end of each step (eligibility check, first or second evaluation stage).
Please check the call text for further information regarding this redress procedure.
