Multi-country Investigator-Initiated Clinical Trials in Cardiovascular, Autoimmune and Metabolic diseases (Trials4Health) JTC2026

The Trials4Health JTC2026 initiative announces a €32.19 million funding opportunity targeting multi-country Investigator-Initiated Clinical Studies focused on cardiovascular, metabolic, and autoimmune disorders. This program aims to enhance pragmatic comparative-effectiveness research and drug repurposing studies through transnational collaboration among clinical and public health research teams within EU Member States and Horizon Europe Associated Countries.

Eligible applicants include research teams and Principal Investigators with requisite experience in clinical trials, while commercial enterprises cannot serve as clinical study coordinators. Each consortium must encompass a minimum of three and a maximum of five participating countries. At least two independent entities must represent different EU Member States or Associated Countries. The nature of the funding is grant-based, with partners funded by their respective national or regional organizations rather than by a centralized EU budget.

The application process is structured into two distinct stages. The first stage involves submitting a pre-proposal, which is subjected to formal checks and external review. Following this, successful consortia are invited to submit full proposals that undergo rigorous evaluation including a rebuttal opportunity and interviews with coordinating investigators. The evaluation criteria emphasize scientific excellence, impact, and the quality of the proposed clinical trial methodology.

Successful projects must focus on Phase III randomized interventional trials and may include a diversity of interventions, ranging from pharmacological treatments to lifestyle adaptations. Drug repurposing studies are encouraged, provided they do not have commercial objectives. Applications must follow strict submission guidelines and ethical standards, with a consideration of Responsible Research and Innovation approaches.

Co-funding is mandatory through national or regional funding entities. Additional budget allowances are available for management activities crucial for supporting the consortium-level efforts. The total length for participation in funded projects can extend up to 48 months, emphasizing collaborative research efforts that significantly address public health concerns.

Submission deadlines are established with the first on January 27, 2026, and the second on June 17, 2026. The initiative encourages comprehensive participation and aims to facilitate high-impact clinical research that contributes to the advancement of healthcare strategies across Europe.

The ERA4Health initiative announces the Trials4Health JTC2026 call, aimed at supporting multi-country Investigator-Initiated Clinical Studies (IICS) focusing on pragmatic comparative-effectiveness trials and drug repurposing studies. The call encourages transnational collaboration among clinical and public health research teams.

The opening date for submissions is November 6, 2025. There are multiple cut-off deadlines, with the first on January 27, 2026, and the second on June 17, 2026, both at 16:00 Brussels time. The expected duration of participation is 48 months. The total funding available is 32,190,000.00 EUR. The project acronym is ERA4Health, and the full name of the EU-funded project is Fostering a European Research Area for Health Research, with grant agreement number 101095426. The topic is HORIZON-HLTH-2022-DISEASE-03-01, which pertains to the European partnership fostering a European Research Area (ERA) for health research.

The call focuses on Phase III randomised interventional trials, requiring appropriate and justified clinical designs. Cluster randomisation may be considered if justified. Comparative effectiveness trials must compare currently approved or existing healthcare interventions used in clinical practice in Europe, either to each other or to the current standard of care. These interventions include diagnostic, screening, prevention, and treatment interventions, encompassing pharmacological and non-pharmacological procedures such as nutritional and lifestyle interventions, surgery, prognosis methods, medical devices, nano and advanced health technologies, eHealth, digital interventions, and other health interventions. Drug repurposing trials should explore new indications for approved off-patent medications, excluding clinical studies with a commercial purpose.

The interventions should have high public relevance in cardiovascular diseases, metabolic disorders, or autoimmune diseases (including antibody-based autoimmune diseases and/or other Immune-mediated inflammatory diseases). Proposals may focus on a single disease or explore these conditions in combination with comorbidities. Applicants should consider Responsible Research and Innovation (RRI) approaches.

The submission and evaluation procedure is in two steps for joint applications. The second step includes a rebuttal stage and an interview with the coordinating investigator and the sponsor's representative. Proposals must be in English, prepared using the ERA4Health template, and submitted by the coordinator via the Pt-outline electronic submission system.

Applicants must demonstrate expertise in all methodological areas required for the proposed study. Principal Investigators should have experience in conducting clinical trials. The consortium should have an appropriate number of participants with a balanced international participation. The project must be transnational, involving eligible research partners from a minimum of 3 and a maximum of 5 different countries participating in the call. At least two eligible partners must be from different EU Member States or Horizon Europe Associated Countries. A maximum of 3 collaborators per consortium is allowed; collaborators are self-funded. Each consortium must nominate a clinical study coordinator who cannot be a commercial enterprise or for-profit organisation. Each Principal Investigator can submit only one pre-proposal as coordinator or partner.

Each clinical study partner will be funded by its national/regional funding organisation, with varying eligible costs and funding rules. Applicants are encouraged to contact their national/regional contact points to check eligibility rules before submission. An additional budget of up to 15% of the total budget requested can be used for cross-cutting management activities, such as trial authorizations, drug, safety, and data management, under the responsibility of the coordinating investigator, through collaboration with ECRIN (www.ecrin.org). Non-eligible partners may lead to the rejection of the entire proposal.

The Joint Call Secretariat (JCS) will check pre-proposals for formal criteria, while national/regional funding organisations will perform administrative checks for compliance with national/regional regulations. External reviewers will evaluate pre-proposals based on scientific/clinical background, clinical trial methodology, and biostatistics. The evaluation includes an eligibility check for the call scope. The Clinical Study Steering Committee (CLSC) will decide which proposals are invited for full proposal submission based on reviewers’ recommendations and budget balance. All consortia will receive evaluation reports, excluding scores.

Full proposals will undergo a similar formal check by the JCS and be allocated to three reviewers with relevant expertise. A Patient Advocacy Committee will assess patient involvement. Coordinators can comment on reviewers' assessments during a rebuttal stage. An online interview with the coordinator and the sponsor's representative will evaluate their capacity to implement the clinical study.

The Peer Review Panel (PRP) will discuss proposals and produce a ranking list. Representatives of the Patient Advocacy Committee will participate in the discussion and have voting rights.

Evaluation criteria for pre-proposals include Excellence, Impact, and Quality and efficiency of the implementation. For full proposals, the criteria include Excellence, Impact, Quality and efficiency of the implementation, Competence of the research team and quality of research environment, and Methods and Design of the clinical trial. A consortium will not be funded if the sponsor lacks the capacity to implement a transnational clinical study.

Evaluation scores will be awarded for each main criterion, scored out of five, with equal weight. The maximum scoring for pre-proposals is 15 points, and for full proposals, it is 25 points. Full proposals must achieve a threshold average score of 3 points per criterion and an overall score of at least 17 points to be considered fundable.

The rebuttal stage allows applicants to comment on factual errors in the review process. The interview of the coordinating investigator and the sponsor's representative will assess their capacity to implement and manage the study. The PRP meeting involves a discussion of all proposals, reviews, rebuttals, and interview outcomes.

Ethics experts will check full proposals for alignment with ethical norms and regulations. Only proposals approved by both scientific evaluation and ethical assessment will be funded.

A first selection of clinical studies for funding will be made by national/regional funding organisations based on the PRP ranking, available funding, and ethical clearance outcomes. Additional studies may be invited to restructure their consortia if funding remains. Coordinating investigators will be informed about funding recommendations, and ERA4Health will publish information on co-funded projects.

Applicants can appeal against the evaluation outcome if they suspect a breach in the evaluation procedures. Appeals must be submitted to the JCS via email (Trials4Health@isciii.es) within 7 calendar days of the eligibility check or evaluation outcome notifications.

In summary, this call aims to fund collaborative, multi-national clinical trials focusing on comparative effectiveness and drug repurposing in cardiovascular, metabolic, and autoimmune diseases. It involves a two-stage application process with rigorous evaluation, ethical review, and a focus on the capacity of the research teams and sponsors to deliver high-quality clinical research. The funding is distributed through national and regional funding bodies, emphasizing the importance of understanding and adhering to local regulations and guidelines.

Eligible Applicant Types: The eligible applicant types include research teams, Principal Investigators, and clinical study coordinators. Specifically, applicants must demonstrate that their research teams possess the necessary expertise in all methodological areas required for the proposed study. Principal Investigators should have experience in conducting and delivering clinical trials. The clinical study coordinator must be nominated from among the partners (not a collaborator) and cannot be a commercial enterprise or for-profit organization. The sponsor organization, according to its legal structure, must have the capacity to implement transnational clinical studies.

Funding Type: The primary financial mechanism is a grant, with each clinical study partner being funded by its relevant national/regional funding organization.

Consortium Requirement: A consortium is required. The project must be a transnational project involving eligible research partners from a minimum of 3 and a maximum of 5 different countries participating in the call. 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 collaborators per consortium is allowed; collaborators are self-funded partners.

Beneficiary Scope (Geographic Eligibility): The geographic eligibility includes EU Member States and Horizon Europe Associated Countries participating in the call. The project must be transnational, involving partners from different countries.

Target Sector: The target sector is health, specifically focusing on cardiovascular, metabolic, and autoimmune disorders. The call supports Investigator-Initiated Clinical Studies (IICS) designed as pragmatic comparative-effectiveness studies and/or drug repurposing studies. Interventions can be pharmacological or non-pharmacological, including diagnostic, screening, prevention, and treatment interventions, such as nutritional and lifestyle interventions, surgery, medical devices, nano and advanced health technologies, eHealth, and digital interventions.

Mentioned Countries: EU Member States, Horizon Europe Associated Countries.

Project Stage: The expected maturity of the project is Phase III randomised interventional trial, focusing on pragmatic comparative effectiveness trials and/or drug repurposing trials. The projects should be designed as Investigator-Initiated Clinical Studies.

Funding Amount: The total funding available is €32,190,000.00. An additional budget of up to 15% of the total budget requested from national/regional funders can be requested for cross-cutting management activities. The funding for each clinical study partner will be provided by its relevant national/regional funding organization, and eligible costs and funding rules may vary.

Application Type: The application type is an open call with a two-step submission and evaluation procedure for joint applications. There are multiple cut-off dates.

Nature of Support: Beneficiaries will receive money through grants, with funding provided by national/regional funding organizations.

Application Stages: The application process involves two main stages: pre-proposal and full proposal.
1. Submission of a pre-proposal, which undergoes a formal check by the JCS (Joint Call Secretariat) and national/regional funding organizations. It is then evaluated by external reviewers.
2. Invitation to submit a full proposal based on the pre-proposal evaluation. The full proposal undergoes a formal check, is evaluated by external reviewers and a Patient Advocacy Committee, and includes a rebuttal stage and an interview with the coordinating investigator and the representative of the sponsor.
3. Ethical clearance of full proposals recommended for funding.
4. Clinical study selection and potential reconfiguration process.

Success Rates: The success rates are not explicitly mentioned, but the process involves multiple stages of evaluation, including formal checks, external reviews, patient advocacy assessment, and interviews, suggesting a competitive selection process.

Co-funding Requirement: Co-funding is not explicitly stated as a requirement, but each clinical study partner is funded by its relevant national/regional funding organization, implying that funding is distributed and managed at the national/regional level. Collaborators are self-funded.

Summary:

The ERA4Health Trials4Health JTC2026 call aims to support multi-country Investigator-Initiated Clinical Studies (IICS) focusing on cardiovascular, metabolic, and autoimmune diseases. The call encourages transnational collaboration between clinical and public health research teams to conduct pragmatic comparative-effectiveness studies and drug repurposing studies. Eligible applicants must form a consortium of 3 to 5 partners from different countries participating in the call, with at least two partners from different EU Member States or Horizon Europe Associated Countries. The call operates through a two-step submission process: a pre-proposal and a full proposal, with evaluations by external reviewers, a Patient Advocacy Committee, and interviews. Funding is provided by national/regional funding organizations, and the total funding available is €32,190,000.00. The call targets Phase III randomised interventional trials and requires a clinical study coordinator who is not a commercial enterprise. The process includes ethical clearance and a potential reconfiguration process to optimize the use of available funding. This opportunity is designed to foster high-impact clinical research and improve healthcare interventions across Europe, focusing on areas of significant public health relevance.