MDCG Publishes Guidance on Clinical Evaluation for Orphan Medical Devices
The Medical Device Coordination Group (MDCG) has published MDCG 2024-10 – Clinical Evaluation of Orphan Devices, providing guidance to support manufacturers in generating and assessing clinical evidence for orphan medical devices under the Medical Device Regulation (MDR).
The guidance recognises the unique challenges associated with orphan devices, particularly the limited availability of clinical data due to small patient populations, and outlines considerations for clinical evaluation, clinical investigations and post-market clinical follow-up (PMCF).
Clinical Evaluation for Orphan Devices
According to the MDCG, manufacturers should ensure that the Clinical Evaluation Report (CER) addresses the specific characteristics of orphan devices, including the limitations associated with generating clinical evidence in rare diseases and conditions.
The guidance recommends documenting the available clinical evidence, identifying remaining evidence gaps and establishing a strategy to generate additional clinical data throughout the device lifecycle using appropriate PMCF activities.
Considerations for Clinical Investigations
The guidance provides recommendations on the design of clinical investigations for orphan devices, acknowledging that traditional randomised controlled trials may not always be feasible due to ethical or practical constraints associated with limited patient populations.
According to the MDCG, manufacturers may consider alternative study methodologies where appropriately justified, including:
Cross-over study designs;
Adaptive study designs;
Sequential study designs;
Prospective observational studies;
Comparative studies using matched or historical controls.
The document emphasises that the chosen study design should be scientifically justified and appropriate for the intended clinical objectives.
Selection of Clinical Endpoints
The guidance highlights the importance of selecting clinically relevant endpoints capable of demonstrating the safety, performance and clinical benefit of orphan devices.
Where disease-specific clinical endpoints are not sufficiently established, the MDCG notes that appropriately validated surrogate endpoints may be considered, provided they are adequately justified. The document also encourages consideration of patient-reported outcomes (PROs) as complementary measures to assess quality of life and patient benefit where appropriate.
Post-Market Clinical Follow-Up
According to the guidance, PMCF plays a critical role in addressing the limitations of pre-market clinical evidence for orphan devices.
Manufacturers are encouraged to establish PMCF plans that may include:
PMCF clinical investigations;
Patient registries;
Collection of long-term safety and performance data;
Continuous assessment of the benefit-risk profile.
The guidance also recommends regular updates of the Clinical Evaluation Report as new clinical evidence becomes available throughout the product lifecycle.
Statistical Considerations
The MDCG acknowledges that conventional statistical approaches may be difficult to apply to orphan device investigations because of the small number of eligible patients.
The guidance discusses alternative approaches, including Bayesian statistical methods and the use of external or historical control data, where scientifically justified and appropriate to support the interpretation of clinical evidence.
Relevance for Medical Device Manufacturers
The guidance is particularly relevant for manufacturers developing orphan medical devices under the MDR, as it provides practical recommendations for generating clinical evidence when traditional study approaches may not be feasible.
Topics of particular interest include:
Clinical evaluation of orphan devices;
Clinical investigation design;
Clinical evidence generation;
Patient-reported outcomes (PROs);
Post-Market Clinical Follow-Up (PMCF);
Benefit-risk assessment;
Statistical approaches for small patient populations.
The publication provides additional clarity on the MDCG's expectations regarding clinical evaluation and lifecycle evidence generation for orphan medical devices intended for the European market.
