Fostering Pragmatic Comparative-Effectiveness Trials in Non-communicable Diseases (EffecTrial)

The ERA4Health EffecTrial Call is a significant funding opportunity aimed at supporting transnational, multi-country Investigator-Initiated Clinical Studies (IICS) focused on pragmatic comparative effectiveness trials. This initiative is particularly designed for research teams engaged in studying non-communicable diseases, including cardiovascular diseases, metabolic disorders, nutrition and lifestyle-related diseases, and respiratory diseases. The program's total funding available is €18,710,000, and the duration of the clinical studies is set for 48 months.

Eligible applicants include universities, research institutes, and nonprofits, with the requirement that the consortium must comprise 3 to 5 countries, demonstrating broad international collaboration. Each consortium must nominate a clinical study coordinator, who cannot be an enterprise. Collaborators within the consortium are expected to be self-funded partners, and the funding for clinical study partners will be allocated through their respective national or regional funding bodies, thus varying in amounts.

The application process follows a two-stage procedure consisting of a pre-proposal and a full proposal stage, which includes an interview and rebuttal phase to assess the coordinator and sponsor's capacity to implement the study. Proposals must be conducted in English and utilize the specified ERA4Health template, submitted via the electronic system designated for the call.

The project aims to compare currently approved healthcare interventions through randomized trials focusing on established therapeutic standards or the use of innovative healthcare solutions including pharmacological and non-pharmacological interventions. The assessment of proposals involves evaluating their scientific excellence, anticipated impact on public health, and the feasibility of implementation.

The submission dates for proposals are crucial, with the opening date for submissions on November 20, 2024, and cut-off dates on January 28, 2025, and June 17, 2025. The evaluation process is thorough, requiring ethical clearance and reviewed by various scientific and clinical experts, as well as a Patient Advocacy Committee to ensure patient relevance and involvement.

Overall, the ERA4Health EffecTrial Call presents an exceptional opportunity for research teams to execute substantial and impactful clinical trials, enhancing healthcare practices and patient outcomes within vital health sectors in Europe.

The ERA4Health EffecTrial Call aims to support randomized, interventional, and pragmatic comparative-effectiveness multi-country Investigator-Initiated Clinical Studies (IICS) and to encourage transnational collaboration between clinical and public health research teams. The call focuses on comparative effectiveness multi-country IICS.

Proposals must meet the following criteria: be a pragmatic comparative effectiveness trial designed as a randomized interventional trial, compare currently approved healthcare interventions to each other or to the current standard of care, and consider healthcare interventions including but not limited to diagnostic, screening, prevention, and treatment interventions. These interventions can be pharmacological or non-pharmacological, such as nutrition and/or lifestyle interventions, surgery, prognosis methods, use of medical devices, eHealth and digital interventions, and other health interventions. The interventions should have high public relevance in the fields of cardiovascular diseases, metabolic disorders, nutrition and lifestyle-related diseases, and non-communicable respiratory diseases. The multi-country IICS should primarily address at least one of these principal diseases/conditions, but proposals can also address several of the mentioned diseases/conditions and/or other related comorbidities. Applicants should consider requirements, recommendations, and out-of-scope conditions, including 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 representative of the sponsor. Proposals must be in English and prepared using the ERA4Health template. Submission is via the Pt-outline electronic submission system tool by the project coordinator.

Applicants must demonstrate that the research team has the necessary expertise in all methodological areas required for the proposed study. Principal Investigators should have experience in conducting and delivering clinical trials. The consortium size and research contribution should be appropriate for the aims of IICS and balanced in terms of international participation. A minimum of 3 and a maximum of 5 countries should be represented in the consortium, excluding collaborators. A maximum of 3 collaborators per consortium is allowed; collaborators are self-funded partners. Each consortium must nominate a clinical study coordinator among its partners, who cannot be an enterprise. Each Principal Investigator can submit only one pre-proposal as coordinator or partner.

Clinical study partners will be funded by their relevant national/regional funding organizations, with eligible costs and funding rules varying accordingly. Each partner should define its budget according to their national/regional 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 from national/regional funders can be requested for cross-cutting management activities, such as trial authorizations, drug, safety, and data management under the coordinating investigator's responsibility. If a partner is found to be non-eligible, the entire proposal may be rejected.

The Joint Call Secretariat (JCS) will check pre-proposals for formal criteria, and national/regional funding organizations will check for compliance with national/regional regulations. External reviewers with scientific/clinical backgrounds will evaluate eligible pre-proposals, considering potential conflicts of interest. The evaluation includes an eligibility check for the call scope. A ranking list will be established based on the scores. The Clinical Study Steering Committee (CLSC) will decide which proposals are invited to submit a full proposal based on reviewers’ recommendations and budget balance. Consortia will receive evaluation reports, excluding scores.

The JCS will check full proposals for formal criteria and consistency with pre-proposals before sending them to reviewers. Each full proposal will be allocated to three reviewers with scientific/clinical backgrounds, including one with expertise in clinical trial methodology and biostatistics. A Patient Advocacy Committee will assess patient involvement and relevance for patient needs. Coordinators can comment on reviewers’ assessments during the rebuttal stage before the Peer Review Panel (PRP) meeting. An online interview of the coordinator and the sponsor representative will assess their capacity to implement the clinical study.

During the PRP meeting, reviewers will discuss proposals and produce a ranking list. Two representatives of the Patient Advocacy Committee will participate in the discussion and present their assessment of patient involvement, with voting rights.

Evaluation criteria for pre-proposals include excellence (scientific relevance, quality, unmet clinical need, previous research), impact (patient benefit, clinical practice, healthcare system, transnational added value, patient involvement, RRI approach), and quality and efficiency of implementation (study design, methodological approach, ethical acceptability, feasibility, research team quality).

Evaluation criteria for full proposals include excellence (innovation, scientific relevance, contribution to knowledge, relevance for patient needs, scientific quality, evidence soundness), impact (transnational collaboration, short-term and long-term impact, potential for patients, public health, clinical practice, socio-economic applications, commercial exploitation, dissemination measures, patient involvement, RRI integration), quality and efficiency of implementation (study design, feasibility, work plan, recruitment, management structures, risk management, RRI resources, regulatory compliance, data management), competence of the research team and quality of research environment (partner competence, skills complementarity, links to networks and infrastructures), and methods and design of the clinical trial (outcome measures, target population, controls/comparators, consideration of consequences, randomization criteria, methods against bias, statistical analysis, sample size).

A consortium will not be funded if the sponsor lacks the capacity to implement the clinical study, regardless of the proposal's scientific quality.

Evaluation scores are awarded for each main criterion on a scale of 0 to 5, with equal weight. The maximum score for pre-proposals is 15 points, and for full proposals, it is 25 points. A full proposal is considered fundable if the threshold score for each criterion is 3 points and the overall score is at least 17 points.

During the rebuttal stage, applicants can comment on factual errors or misunderstandings in the review process. The rebuttal period is 12 calendar days (August 25 to September 5, 2025).

The coordinating investigator and the sponsor representative will be interviewed by an interview committee to determine their capacity to implement and manage the clinical study. PRP members will receive feedback from the interview committee.

The JCS will provide PRP members with access to all proposals, reviews, rebuttals, and interview outcomes, avoiding conflicts of interest. The PRP will assign final scores, classify proposals, and rank proposals recommended for funding.

Ethics experts will check full proposals recommended for funding for alignment with ethical norms and regulations. Clarifications may be requested from the consortium. 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 organizations based on the PRP ranking list, available funding, and ethical clearance outcomes. Additional clinical studies may be invited to restructure their consortia if there is remaining funding. Restructuring must meet the eligibility criteria of the call.

If a crucial clinical study partner or the coordinating investigator withdraws, is ineligible, or cannot fulfill their commitment, the proposal is irrevocably disqualified without the opportunity for restructuring.

Coordinating investigators will be informed about the funding recommendation by the JCS and are responsible for communicating this information to their partners.

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

The opening date for submissions is November 20, 2024. The deadline dates are January 28, 2025, and June 17, 2025, both at 16:00 (Brussels time). The expected duration of participation for the clinical studies is 48 months. The total funding available is 18,710,000.00 €. The project acronym is ERA4Health, and the full name of the EU-funded project is Fostering a European Research Area for Health Research. The grant agreement number is 101095426. The topic is HORIZON-HLTH-2022-DISEASE-03-01 - European partnership fostering a European Research Area (ERA) for health research.

In summary, this call aims to fund multi-country clinical studies that compare the effectiveness of existing healthcare interventions for cardiovascular diseases, metabolic disorders, nutrition and lifestyle-related diseases, and non-communicable respiratory diseases. It involves a two-stage application process with strict eligibility criteria, a thorough evaluation process including scientific review, patient advocacy input, and ethical assessment, and a focus on transnational collaboration and responsible research and innovation. The funding is distributed through national and regional funding organizations, and consortia must demonstrate the capacity to conduct high-quality clinical trials with significant impact on patient care and public health.

Eligible Applicant Types: The eligible applicant types are clinical and public health research teams. The Principal Investigators should demonstrate experience and expertise in the conduct and delivery of clinical trials. Each study consortium must nominate a clinical study coordinator among its partners, and the clinical study coordinator cannot be an enterprise. Applicants must demonstrate that the research team contains the necessary breadth and depth of expertise in all the methodological areas required to deliver the proposed study.

Funding Type: The funding type is a grant, where clinical study partners will be funded by their relevant national/regional funding organisations.

Consortium Requirement: A consortium is required. Only transnational studies will be funded. A minimum of 3 and a maximum of 5 countries should be represented in the consortium. A maximum of 3 collaborators per consortium is allowed, and collaborators are self-funded partners.

Beneficiary Scope (Geographic Eligibility): The geographic eligibility is transnational, requiring a consortium with partners from a minimum of 3 and a maximum of 5 countries. The specific eligible countries are determined by the national/regional funding organizations participating in the call, as detailed in Annex I of the call documents. Applicants are strongly encouraged to contact their national/regional contact points to check their national/regional eligibility rules before submission.

Target Sector: The target sector is health, specifically focusing on Investigator-Initiated Clinical Studies (IICS) in the following disease areas: Cardiovascular diseases, Metabolic disorders, Nutrition and lifestyle-related diseases, and Non-communicable respiratory diseases. The call supports pragmatic comparative effectiveness trials that compare currently approved healthcare interventions (pharmacological and non-pharmacological) to each other or to the current standard of care, including diagnostic, screening, prevention, and treatment interventions, use of medical devices, eHealth and digital interventions, and other health interventions.

Mentioned Countries: No specific countries are mentioned in the provided text, but the requirement for a transnational consortium implies that the opportunity is open to multiple countries, depending on the national/regional funding organizations participating in the call. Applicants need to refer to Annex I and national/regional announcements to determine eligible countries and regions.

Project Stage: The project stage is development, validation, and demonstration, focusing on Investigator-Initiated Clinical Studies (IICS) that are interventional and pragmatic comparative effectiveness trials. The call aims to support studies that compare the use of currently approved healthcare interventions.

Funding Amount: The total funding available is 18,710,000.00 €. The funding for clinical study partners will be provided by their respective national/regional funding organizations, and the specific funding amounts may vary. An additional budget representing up to 15% of the total budget requested to the national/regional funders could be requested for covering the conduction of cross-cutting management activities.

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: The beneficiaries will receive money through grants, with funding provided by national/regional funding organizations. An additional budget can be requested for cross-cutting management activities.

Application Stages: The application process involves two stages: a pre-proposal stage and a full proposal stage. 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.

Success Rates: The success rates are not explicitly mentioned, but the process involves multiple evaluation stages, including eligibility checks, external reviews, a Clinical Study Steering Committee (CLSC) decision, a Peer Review Panel (PRP) meeting, and ethical clearance, suggesting that the success rate is likely to be competitive.

Co-funding Requirement: Co-funding is not explicitly stated as a requirement, but collaborators within the consortium are self-funded. The primary funding comes from national/regional funding organizations, and applicants are encouraged to define their budget in accordance with the funding rules of their own country/region.

Summary:

The ERA4Health EffecTrial call is a funding opportunity aimed at supporting transnational, multi-country Investigator-Initiated Clinical Studies (IICS) focused on pragmatic comparative effectiveness trials. The call seeks to encourage collaboration between clinical and public health research teams to compare currently approved healthcare interventions for cardiovascular diseases, metabolic disorders, nutrition and lifestyle-related diseases, and non-communicable respiratory diseases. The application process is divided into two stages: pre-proposal and full proposal, with evaluations by external reviewers, a Clinical Study Steering Committee, and a Peer Review Panel, including a rebuttal stage and an interview for the coordinating investigator and sponsor representative. Ethical clearance is also required. Consortia must include partners from a minimum of 3 and a maximum of 5 countries, with funding provided by the respective national/regional funding organizations. The total funding available is 18,710,000.00 €, and the initial duration of the clinical studies will be 48 months. This call provides a significant opportunity for research teams to conduct impactful clinical trials and contribute to improving healthcare practices and patient outcomes in key disease areas.