2025 - BeNeFIT 4: call for comparative effectiveness studies

In September 2024 the Belgian Health Care Knowledge Centre (KCE) and The Netherlands Organisation for Health Research and Development (ZonMw) agreed to invest 9.2 million euros in the fourth call of the Belgium-Netherlands Funding of International Trials (BeNeFIT) program. In March 2025, the total available budget was increased to 10.8 million euros.

In clinical practice, many treatments have not been thoroughly evaluated, making it unclear whether a patient benefits from a particular treatment, or which treatment is actually preferable. Evaluation of clinical practice is relevant to health care stakeholders in Belgium and the Netherlands and by working together, clinical evaluation trials can be carried out more quickly and efficiently.

Health care efficiency research compares the effectiveness and cost-effectiveness of treatments that are part of health care in daily practice. Studies are focused on health benefits for the patient, but also evaluate costs. In Belgium the government finances these studies through KCE Trials and in the Netherlands funding is provided by the ZonMw programs ‘Efficiency Studies’ and ‘Rational Pharmacotherapy’, commissioned by the Ministry of Health, Wellbeing and Sports.

In 2017 KCE Trials and ZonMw launched the joint program BeNeFIT. In this initiative, a new funding selection process was developed that integrates approaches from both organisations. The main focus of the program is to provide funding for non-commercial practice-oriented research that is immediately relevant to patients, caregivers and policymakers in Belgium and the Netherlands and is conducted in collaboration by research institutions from both countries.

Selection of research outlines submitted to this fourth BeNeFIT call has taken place in April 2025. The BeNeFIT call steering committee (CSC) now invites selected research teams to submit their full research proposal (FRP).

Scope

The BeNeFIT call focuses on comparative effectiveness trials which show clear value for money and have the potential for return on investment. Comparative effectiveness trials compare the benefits and harms of different treatment options (with ‘no treatment’ or placebo being one of the possible treatment options) that are already in use in the health care system for the given indication but which have never been adequately compared directly (i.e. which of 2 treatments work better in daily practice). Studied interventions must already be in use in daily practice for the studied indication in both countries. Accepted study interventions are not limited to drugs or medical devices but also include a broad range of interventions, such as psychotherapy, diet, diagnostic tests or surgery. Proposals will be selected based on the need for evidence in clinical practice, possible efficiency improvement and potential return on investment for the health care systems. The primary aim of the trial should be of a non-commercial nature.

Out of scope

• If the primary aim of the studied intervention is to promote the uptake of research findings, the study is considered implementation research, which is out of scope. Interventions that aim to improve implementation of guidelines or quality of care are also out of scope.
• Health services research that studies the organisation of care (at macro, meso or micro level). This call offers no scope for research involving organizational innovations, such as task rearrangement, offering the intervention at another location or logistical organization of care.
• Interventions that have been used only within the framework of clinical research or pilot testing are out of scope.
• Studies of medicinal products or medical devices that are not marketed in Belgium and The Netherlands. Devices should have a CE label. Off-label use that is well established in usual care is accepted.
• Prevention, screening (early detection) or tests to predict risk or response. An exception is healthcare-related prevention, including relapse prevention. Preventive measures that target a group of patients with an existing condition and aim to reduce complications, limitations, or mortality, or increase quality of life are in scope.
• Studies that already have been submitted to authorities, ethical committees and/or have already started recruitment.
• Interventions that are not eligible for possible reimbursement in at least one of the two countries

Deadline

2nd September 2025 14.00h

Who can submit

Research teams from institutions in Belgium and the Netherlands that have been selected and invited to submit a FRP by the CSC can further apply to this call. The sponsor* (the main applicant, who shall also be the sponsor of the Trial under ICH/GCP) should be located in one of the two countries and should be supported by a national coordinating centre in the other country.** Both Belgian and Dutch centres should participate, ideally with a good regional spread. In Belgium, centres from all regions (Flanders, Wallonia and Brussels) should participate, ideally with a good regional spread.

* As defined in ICH-GCP

** In case of co-sponsorship: co-sponsors must enter into an agreement that complies with applicable laws and the provisions of the Terms and conditions of the Third Benefit Call. All co-sponsors will be jointly and severally liable towards the Funding Agencies for the compliance with the provisions of these Terms and Conditions and (if applicable) with the provisions the research agreement that incorporates them. In case of co-sponsorship, one co-sponsor must act as main applicant.

Additional country-specific criteria

Belgium

In Belgium, the sponsor or the national coordinating centre should qualify as non-commercial sponsor under the applicable laws, including the Belgian law related to experiments on human people (May 7th, 2004).
Participating centres should include at least one centre from each region of the country (Flanders, Wallonia, Brussels)$
The funding granted under the research agreement complies with the European state aid regulations.

The Netherlands

In the Netherlands, the sponsor or the national coordinating centre must be a research organisation or care institution^p.
At least one of the participating institutions in the Netherlands should be a non-academic hospital.$
Studied interventions should be (or have the potential of being) reimbursed under the “Basic Health Care” Act and/or the “Long Term Care” Act packages (“basispakket Zorgverzekeringswet” and “Wet langdurige zorg”) in The Netherlands.
Studies should fall within the scope of the “Efficiency Studies” (DoelmatigheidsOnderzoek) program or the “Rational Pharmacotherapy” (Goed Gebruik Geneesmiddelen) program of ZonMw. For detailed information please consult the website of ZonMw.

p Definition (OOI kaderregeling): Onderzoeksorganisatie en zorginstelling (artikel 5, lid 1, wet toelating zorginstellingen)

$If not possible, please justify