The EU Member State authorities responsible for clinical trials and medical devices and the European Commission jointly launched the COMBINE initiative in June 2023. The aim of the initiative is to analyse the challenges that sponsors face in conducting combined studies and to find possible solutions. Combined performance studies linked to CDx (companion diagnostics) are clinical studies that investigate both the efficacy of a medicinal product and the performance of an associated diagnostic test (CDx). There is significant involvement in the project by two German authorities – the Paul-Ehrlich-Institut (PEI), Federal Institute for Vaccines and Biomedicines, and the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) – along with the medical ethics committees. The goal of their participation is to simplify and accelerate the procedures for approving CDx performance studies conducted in parallel with clinical trials.
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The COMBINE programme consists of two phases. The first phase – the analysis phase – was completed with the publication of the analysis report in May 2024. The analysis report provides solutions to the primary challenges that sponsors face when conducting combined studies. One such challenge is the complexity of the combined studies, which require that several regulations be simultaneously applied and complied with – Regulation (EU) 536/2014, Clinical Trials Regulation (CTR); Regulation (EU) 2017/745, Medical Devices Regulation (MDR); and Regulation (EU) 2017/746, In Vitro Diagnostic Medical Devices Regulation (IVDR).
The second phase of the COMBINE programme is currently underway – the development phase: several individual projects will now flesh out and further develop some of the solutions presented in the analysis report.
The first individual project kicked off the first phase of its pilot process in June 2025. In this phase, the feasibility of a coordinated evaluation procedure using the Clinical Trials Information System (CTIS) is being investigated for applications that include a multinational clinical trial of an investigational medicinal product in combination with an interventional clinical performance study of an in vitro diagnostic medicinal product or a concomitant diagnostic medical device from the same sponsor. This "all-in-one" coordinated procedure is intended to streamline the marketing authorisation process, reduce the administrative burden for sponsors and accelerate access to innovative treatment concepts for patients.
Sponsors interested in participating in this pilot are asked to submit an expression of interest form and a synopsis of the planned combined study via Eudralink to EUcombinepilot@ccmo.nl by 31 August 2025. Further details as well as the prerequisites for participation can be found on the COMBINE website.
Sponsors who express their interest in participating before the deadline will be informed no later than 31 October 2025 as to whether their application has been selected for the COMBINE 1 pilot project.
Updated: 31.07.2025
