Combined studies: Commission officials outline proposed reforms

BRUSSELS – European Commission officials say they have proposed legislative changes to the European Parliament that they hope will ease regulatory requirements for sponsors of combined studies based on ongoing pilot projects.

Olga Tkachenko and Isabelle Clamou, European Commission policy officers, spoke to attendees at the 2026 DIA-RAPS Combination Products in the EU conference about what the Commission had learned so far from the projects and how they have used that to propose legislative amendments to the Medical Device Regulation (MDR), In Vitro Diagnostic Regulation (IVDR), and Clinical Trials Regulation (CTR).

Under its COMBINE program, the European Commission has been working to better understand how combination products that include medical devices, drugs and diagnostics are developed and regulated. The objective of the program is to find ways to simplify and harmonize regulatory requirements to enhance patient access to medical products and boost market competitiveness in the economic zone.

Tkachenko said that the Commission has proposed using certain definitions to ensure that everyone is on the same page. She noted that they have been using a definition of combined studies during the COMBINE program that they proposed to formalize in the MDR, IVDR, and CTR. Moving forward, a combined study would be defined as a clinical trial that is combined with a performance study and/or a clinical investigation and can be a configuration of all of the above.

"One other definition I wanted to highlight from the device from the IVDR is the companion diagnostic definition," said Tkachenko. "The proposed amendment is to make it absolutely clear that it's possible to have one or more corresponding medicinal products.

"It's not only one device, one drug, but there can be one device for several different drugs," she added.

Tkachenko highlighted that the Commission proposed allowing laboratories that manufacture and use IVDs in the European Union for exclusive use in a clinical trial to receive regulatory exemption as in-house devices that are already in Annex 1 of the IVDR. Furthermore, she said that they are proposing much greater use of expert panels, including allowing manufacturers to get advice on their intended strategy for demonstrating clinical performance or for clinical performance studies. She also noted that the panels could provide more regulatory advice, especially considering that they can include experts from notified bodies and competent authorities.

Tkachenko also echoed comments from a presentation she gave the previous day where she noted that the Commission wants to simplify the authorization and notification requirements for performance studies. More specifically, it has proposed not requiring authorization studies for low-risk surgically invasive sampling and notification for companion diagnostics studies that use left-over samples. (RELATED: EU officials detail proposed MDR, IVDR revisions, Regulatory Focus 27 January 2026)

The regulators also said the Commission has proposed significant changes to amend the CTR to simplify how combined studies are conducted.

"We started the COMBINE program because of your challenges with interplay between the three regulations, and we heard your screams, 'Make it simpler, please,'" said Clamou. "This is what we tried to do with the provisions in the regulation."

Clamou noted that the COMBINE program is still ongoing and the Commission is looking to make future recommendations based on what they learn about the pilot projects that they intend to include in a delegated act. She said it would allow them to propose further amendments or add supplements to the CTR including changes to the authorization procedures for clinical trials and substantial modification of clinical trials, application dossiers, trial subject protections and informed consent, safety reporting, and IT infrastructure.

"A delegated act is an empowerment to the European Commission to develop procedures or elements which will then be developed later, but which have a strong legal basis in the mother regulation," said Clamou. "The details of the procedures are not yet in the regulation, but the core elements of the future of combined studies are in the article."

For instance, the proposal recommends that if manufacturers need authorization for a performance study that is part of a combined study, the requirements in the CTR and the delegated act would override requirements in the MDR and IVDR. It also allows sponsors conducting a combined study in one or more member states to submit a single authorization application.

The Commission also wants to allow combined study sponsors to submit their application electronically through the EU Portal, which is the Clinical Trial Information System (CTIS), to all member states in which the studies are conducted. In instances where there is more than one sponsor of the studies, a coordinating sponsor will be designated.

Clamou said they made the choice to use CTIS for this purpose instead of EUDAMED, which is intended for medical devices, because it is still under construction and CTIS was already being used in the COMBINE program.

"We are very conscious that for device developers, it will mean getting familiar with the united system, new terminology, etc.," said Clamou. "Hence the importance of the training and [the European Medicines Agency (EMA)] is already aware that they should work on that."

Another important proposed change to the CTR would clarify that ethics committees will be involved in the review process. Clamou said it would limit the concerns member states and ethics committees are able to raise to streamline the coordinated assessment process. She also said the Commission is recommending that the authorization conclusion covers both the device and the IVD.

"This is very important down the line for the provisions related to combination products, because you will have one conclusion on the entire assessment and the conclusion should be deemed to be the conclusion of all members concerned," said Clamou. "One single decision regarding the combined study, we hope, will make your life much simpler."

Clamou noted, however, that the delegated act is not a blank check to the Commission and the changes proposed are limited to what is in the proposal.

"Because we are in the CTR, the delegated act will be provisions amending or supplementing existing chapters of the CTR, plus taking into considerations the relevant articles of the MDR and IVDR,” she added.

Clamou also said that that the Commission has proposed language that would add language on use of artificial intelligence (AI) in clinical trials. For instance, the proposal would state that when sponsors plan to use AI in clinical trials, they would be required to evaluate benefits- risks to patient safety and how it affects the data while considering the guidelines set in the Biotech Act. Sponsors would also be required to provide information in their protocol on the specific purpose of the use of AI in the clinical trial and a description of the process.

"We are aware that it is now becoming normal to use AI in medicine, state government and some AI tools and systems qualify as devices," said Clamou. "We have made it clear that when these scenarios occur, then the combined studies coordinated assessment and procedures would apply."

She said their intention is to make things easier for sponsors and allow them to hasten their uptake of AI in clinical development but noted that that it doesn't mean they are authorizing the AI but rather the combined studies that use AI.

Tkachenko emphasized that the proposed legislative changes have been shared with the European Council and the European Council that still need to be negotiated.

"The things that we have presented to you, they may not stay the way that they are now, but we will see and we look forward to the outcome of those negotiations," she added.

2026 Combination Products in the EU

Combined studies: Commission officials outline proposed reforms

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