One medical device regulation, many country interpretations: lessons learned from EHRA-PATHS software tool use in a clinical trial
L Desteghe, R Onder, C Van Deutekom, E L Maas-Soer, I C Van Gelder, M Rienstra, H HeidbuchelAbstract
Background
Within the EHRA-PATHS project, 23 concise care pathways were developed to identify and manage comorbidities and risk factors in atrial fibrillation (AF). These pathways were integrated into a software tool, offering clinicians a structured approach to comorbidity management. The software is currently under evaluation in a European randomized controlled trial. Since 2017, the European Union Medical Device Regulation (MDR) has been in place, stating that software can be a medical device, depending on its intended purpose. A guidance document on software qualification and classification was published in 2019 and updated in 2021.
Purpose
To evaluate how various European countries interpreted and implemented the MDR regulations, leading to different regulatory and ethical approval procedures.
Methods
A tailored questionnaire captured experiences of 14 national principal investigators (PIs) regarding submission of the EHRA-PATHS trial under the MDR in their countries. Although not CE-marked, the software was developed in compliance with the MDR safety principles and the General Data Protection Regulation (GDPR) privacy standards. Clinical trial initiation was sought in 14 European countries (1–6 centers per country).
Results
In November 2023, the Sponsor’s central ethics committee in the Netherlands approved the study under MDR Article 82. Of the 14 countries, six considered the trial to be outside the scope of the MDR. Among the remaining eight, submissions varied: three under Article 82, one under Article 62, one under Regulation 30 UK MDR 2002, and three did not have to specify the article. Also the organizations/authorities that evaluated the study and its documents showed significant diversity (Figure 1). In nine countries, a national authority was in place, sometimes combined with a central/national (n=4) or regional/local ethical committee (n=3). Required documents and submission procedures varied depending on the interpretation of the applicable MDR article and on the country. In five countries, a submission platform was in place to upload all information and documents, while other countries still used email, paper or CD. In two countries (Spain and the United Kingdom) the submission process was stopped due to complexity, contractual or cost issues. Despite two submissions and a personal discussion possibility between investigators and regulators, no approval to start the study could be received in Sweden. Approval required zero to four review rounds in the other countries.
Conclusion
Despite a unified MDR framework, national interpretations and processes differ substantially to start a clinical trial involving a new, rather simple, software tool. This creates uncertainty for applicants and regulators. Better harmonized pathways are needed to avoid regulatory fragmentation and to support innovation in clinical research.Figure 1