Author: Pawandeep Kaur Bollinger, PhD
Early feasibility studies (EFS) are critical for accelerating the development of innovative medical devices, particularly under the EU Medical Device Regulation (MDR). These studies provide preliminary safety and performance data, enabling developers to iterate designs and address risks before full-scale clinical trials. However, the harmonization of EFS frameworks remains a challenge in Europe. This blog explores the current landscape, highlights collaborative initiatives, identifies gaps, and offers perspectives for improvement.
EFS are small-scale investigations designed to assess the viability of a medical device in humans. Under the MDR, they fall under "pilot clinical investigations" and include first-in-human studies, early feasibility trials, and traditional feasibility studies. These studies focus on safety by identifying immediate risks and adverse events, performance by evaluating whether the device achieves its intended purpose, and design iteration by informing modifications before pivotal trials. Unlike confirmatory studies, EFS data alone cannot support CE marking but are vital for refining high-risk devices, such as Class IIb/III implants.
The MDR aims to standardize clinical investigation requirements across the EU, replacing the fragmented directives that allowed member states to set their own rules. Key harmonization measures include compliance with ISO 14155:2020, which outlines Good Clinical Practice (GCP) for medical device studies, ensuring consistency in trial design and ethics. The Medical Device Coordination Group (MDCG) provides Q&A documents clarifying EFS requirements, such as safety reporting and study design. Initiatives like the BFCC project (Baltic Fracture Competence Centre) demonstrate regional collaboration to align EFS with MDR post-market surveillance (PMS) and adverse event tracing.
Despite these efforts, gaps in harmonization persist. Manufacturers report variability in how Notified Bodies (NBs) interpret clinical data sufficiency, particularly for legacy devices. The MDR does not mandate randomized controlled trials (RCTs) for most devices, leading to heterogeneous evidence quality. Ethical review processes differ across EU member states, complicating multi-country EFS.
Several groups are working to streamline EFS under the MDR. The BFCC Consortium, a hospital-industry partnership in the Baltic Sea Region (BSR), focuses on MDR-compliant feasibility studies for orthopedic implants. Their work includes adverse event tracing and integrating PMS data into registries. MDCG Expert Panels review clinical evaluation reports (CERs) for high-risk devices to ensure alignment with MDR requirements. The upcoming Health Technology Assessment (HTA) Regulation (HTAR) plans joint scientific consultations to align clinical investigations with payer evidence needs, potentially reducing post-market evidence gaps.
Significant barriers persist despite progress. CE-marking submissions remain confidential, limiting access to clinical evidence for payers and researchers. Only 39% of high-risk device applications in Belgium included RCTs, and 22% lacked data beyond 12 months. Small and medium-sized enterprises (SMEs) struggle with the cost of generating MDR-compliant clinical data, risking market withdrawal. Stricter MDR equivalence criteria force manufacturers to conduct new trials, even for incremental innovations.
To address these gaps, stakeholders propose legislative reforms to mandate comparative RCTs for high-risk devices and enforce common specifications for study designs. Public-private partnerships should be expanded to other regions, leveraging registries for real-world data collection. Enhanced transparency through the publication of anonymized CERs and PMS reports could support evidence-based decision-making. Investments in MDR-specific clinical evaluation training for manufacturers and NBs could reduce interpretation inconsistencies.
Early feasibility studies are pivotal for navigating the EU MDR’s rigorous clinical evidence requirements. While harmonization efforts like MDCG guidance and ISO standards provide a foundation, gaps in transparency, resource allocation, and regulatory consistency remain. Collaborative frameworks and policy reforms are essential to ensure innovative devices reach patients without compromising safety or stifling SME innovation.
Key Resources:
- MDCG Q&A on Clinical Investigations
- KCE Report on Evidence Gaps in High-Risk Devices
- PMC Study on MDR Clinical Evaluation Challenges
- Health technology assessment
For further details, explore the linked guidelines and regulatory databases.
Need support navigating these guidelines?