On 13 June 2025, the European Commission launched the first phase of a pilot project under its COMBINE programme (the pilot project), aiming to streamline the authorisation process for combined studies involving both clinical trials of medicinal products and performance studies of in vitro diagnostic medical devices (IVD) (referred to as combined studies below).
The pilot project represents a significant step towards addressing the complex and fragmented regulatory landscape that sponsors currently face when submitting applications for combined studies across multiple EU countries. Although its practical effectiveness remains to be seen, the pilot project represents a positive development that should facilitate the approval of combined studies in the EU.
The pilot project is the first initiative under the COMBINE programme, with additional projects planned to launch in the coming years.
What is the COMBINE programme?
The COMBINE programme is an initiative developed following the Draghi report to support EU competitiveness in clinical research. It seeks to harmonize and simplify the complex regulatory environment that currently applies to combined studies, and one that has been the source of much criticism, as well as delays and expense for sponsors.
First launched in 2023, the COMBINE programme was created to investigate and address the growing challenges encountered by sponsors when conducting combined studies. These are studies that include both a clinical trial of a medicinal product and either a clinical performance study of an IVD or a clinical investigation of a medical device.
The regulation and conduct of combined studies fall within multiple overlapping, but separate, EU regulatory frameworks, includingRegulation (EU) 536/2014 on clinical trials on medicinal products for human use (CTR), Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), and Regulation (EU) 2017/745 on medical devices (MDR). Each regulation sets out its own authorisation requirements, and due to a lack of harmonisation and differences in how these are implemented across EU countries, this often results in a fragmented and burdensome process for sponsors. This is particularly the case for studies involving both a medicinal product and a medical device or IVD, as often different authorities review the trial documentation and may come to different conclusions on the same trial. This has been a major source of criticism under the MDR and IVDR.
Under the first phase of the COMBINE programme, an analysis report was published in May 2024, the findings of which served as a basis for planning and implementing future work to address ongoing challenges with combined studies in a structured and strategic manner. In December 2024, Member States endorsed the second phase strategy consisting of several projects, of which the pilot project is the first to be commenced.
What is the pilot project?
The pilot project aims to synchronize the assessment of the authorisation and ethics review processes for multinational combined studies and, specifically, the first phase of the pilot project targets combined studies involving a medicinal product and an IVD.
The key elements of the pilot project are as follows:
- Single entry for submission: sponsors will submit all relevant documents through Clinical Trials Information System (CTIS, the centralised system for clinical trials in the EU). This will simplify the process for sponsors, as it will not be necessary to make multiple national submissions. While this process already operates for clinical trials of medicinal products, a single submission is not yet possible for IVDs, although our previous blog post sets out a separate pilot scheme on the coordinated assessment for clinical investigations of medical devices between Member States.
- Aligned review timelines: the aim is to align decision-making timelines of national competent authorities and ethics committees involved in the authorisation and review of the clinical trial and the performance study across the EU countries involved. The intention is for a final decision by day 81 from the date of validation of the application.
- Coordinated requests for information (RFI): sponsors will receive a single set of RFIs from the Reporting Member State (i.e. an EU country acting as the coordinator), instead of receiving RFIs separately from each EU country. Sponsors can then respond to all RFIs in one go, hopefully removing fragmentation and duplication of work.
Who can participate?
The pilot project is currently open to a limited number of eligible combined study applications. In particular, eligible combined studies must meet the following criteria:
- Involve a medicinal product and an IVD: The combined study must involve a clinical trial of a medicinal product and an interventional clinical performance study of an IVD or companion diagnostic (CDx).
- Multi-national: The combined study must be conducted in more than one EU country.
- One single sponsor: The sponsor must be the same for both the clinical trial and the performance study.
- Well-defined endpoints: The performance study of the IVD must be well defined with endpoints.
Combined studies involving a clinical investigation of a medical device, and those involving a clinical trial of an advanced therapy medicinal product (ATMP) are not eligible in this phase of the pilot project.
Next steps
Sponsors interested in taking part of the pilot project must submit an expression of interest form and a synopsis of proposed combined study to EUcombinepilot@ccmo.nl by 31 August 2025, and those selected will be notified by 31 October 2025.
For more information on the pilot project, the European Commission will host a webinar for sponsors on 20 June 2025.
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