Pilot on combined studies to simplify rules, boost innovation and help patients
date: 17/06/2025
What is the COMBINE ‘all-in-one’ pilot and what is its aim?
The conducting of combined clinical studies poses specific challenges and has been much debated. The main aim of the COMBINE pilot is to streamline the assessment process for multinational clinical trials (medicines) with a simultaneous clinical investigation / performance study (devices) by synchronising the reviews by competent authority and ethics committee. To fully appreciate why the Member States and the Commission deemed it necessary to pilot this procedure, let’s recall what combined studies are and what the authorisation processes for doing this type of studies look like until now.
Combined studies are clinical studies looking at multiple, linked healthcare products, like a medicine coupled with a delivery device or a companion diagnostic. In the EU, there are different regulations for the individual authorisation processes of clinical trials for medicines on the one hand, and clinical investigations for medical devices or performance studies for in vitro diagnostics (IVDs) on the other hand. This can lead to administrative red tape and challenges. Sponsors of these studies have to fill in parallel paperwork and apply for separate assessment processes, which can cause unnecessary duplication.
In addition, different approaches among national competent authorities authorising the studies can slow down the process. These complications can cause delays in studies taking place, which in turn may delay patient access to innovative treatments.
How will the pilot help simplify things?
What the COMBINE ‘all-in-one’ pilot project does, is to explore synchronising the reviews of national authorities and ethics committees into a single process per combined study. This will be achieved by facilitating a simultaneous submission, validation, and assessment, and by aligning the timing of the required authorisations/decisions for multinational combined studies. We call it the ‘all-in-one’ assessment.
The pilot framework was built around coordinating activities between the parties involved in assessing and reviewing study applications, i.e. the multiple authorities and ethics committees. To achieve this goal, all the relevant documentation has to be gathered and made available in one location and the respective timelines across the different regulations have to be aligned.
Through the pilot approach, one Member State, the ‘reporting Member State’, takes the lead and coordinates the requests for information for both the medicine side and the companion diagnostic device side on behalf of all participating Member States. The sponsor receives the coordinated requests for information simultaneously and provides a single response for questions raised on both the clinical trial and the performance study aspects. In this way, the process becomes more efficient and streamlined, reducing delays and promoting consistency across Member States.
Who has been involved in developing the project?
The COMBINE initiative began in June 2023, when the European Commission, national competent authorities for clinical trials and medical devices, and ethics committees came together to tackle the challenges sponsors and regulators face with combined studies.
We started by analysing the root causes of these challenges and identifying potential solutions. Coordinated assessment of study applications was one of the key ideas that emerged. Fast forward two years, and we have now launched a call for expression of interest to participate in the pilot and have published our first pilot sponsor guide. It has been a real team effort, involving national regulators, the European Medicines Agency, ethics committees, and stakeholders like sponsors, clinicians, and patient representatives with a new project management approach.
The launch of this pilot is just the beginning, as COMBINE is actually a broader programme made up of seven cross-sector projects.
Tell us more about the upcoming event on 20 June 2025
On 20 June, from 14.00 to 16:00 CEST, we are hosting a webinar that will be a great opportunity for potential sponsors to learn about this pilot ‘all-in-one’ procedure. The pilot is currently focused on the most common format of combined studies: that of a medicine with an interventional clinical performance study of an IVD. Potential sponsors will hear about resources available to them for the pilot and how to respond to the ‘call for expression of interest’. We will be with the competent authority leads of the pilot and plan to cover a lot of useful information. Anyone interested is most welcome to join us, using the link provided below.
More information: