Set For Success: Avoiding The Pitfalls Of Clinical Data Conformity In Medical Device Trials

Contributed Commentary by Richard Bassett, Director, Regulatory Affairs, ICON

January 24, 2025 | The Medical Devices Regulation 2017/745 and the In Vitro Diagnostic Regulation 2017/746 have greatly enhanced the requirements related to the performance, conduct, monitoring, recording and reporting of medical device clinical investigations in the European Union (EU). The requirements in the legislation now align with, and improve upon, the relevant clinical standards (ISO 14155 for medical devices and ISO 20916 for invitro diagnostics) which has made the once voluntary clinical requirements now mandatory for all medical device clinical investigations. This tightening of clinical requirements under the EU Regulations has been cited as a key issue in the claims that medical devices are disappearing from use within the EU.

Although the EU still relies on international standards and guidance to help manufacturers interpret the principles laid out in the regulations, the standards and guidance do not prescribe how to complete the work, nor do they provide a specific criterion for certain device requirements. This is a particular issue for clinical evidence requirements where the amount of clinical evidence deemed sufficient to support device claims must be determined by the manufacturer. In consideration of this fact, it can be confidently stated that irrespective of device risk classification, determining the amount of clinical evidence required poses the greatest challenge for medical device manufacturers.

Challenges Navigating Clinical Requirements

One study completed in 2022 interviewed employees from a range of medical device manufacturers to survey the issues found with the new requirements of the MDR. The study asked a question relating to the struggle of implementing the clinical requirements; the top challenges identified by respondents included “skills and knowledge gap” (32%) and sourcing clinical data (16%).

The ‘skills/knowledge’ gap highlighted by almost a third of respondents in this survey will inevitably lead to noncompliant documentation which could result in failed conformity assessment and, in some cases, business closure.

Minding The Gaps In Clinical Evaluation Reporting

Another study in the same time period assessed 114 Clinical Evaluation Reports (CER) from medical device manufacturers in order to review their level of compliance to the MDR. The project identified a number of gaps ranging in severity; at least 49 studies had at least one gap that ranked “most severe”.

This study showed that significant gaps were seen in the majority of CERs reviewed, which supports the previously raised concerns regarding the interpretation of clinical requirements. In addition to these study results, Expert Panel Clinical Evaluation Consultation Procedure (CECP) Reports have been made publicly available and once again we can see that the gaps highlighted in these studies have come to fruition within the submitted clinical documentation.

Addressing Ambiguity For A Path Forward

One of the repeated areas of non-conformance seen in the CECP Reports include reference to the quality of clinical data and the ability to accurately determine the clinical benefit. Further issues can be seen in the limited follow-up time and small sample size as well as concerns regarding equivalence. It is reasonable to believe that this trend has continued since these reports were published. Although a number of supporting documents have been issued at the time of writing this article, including guidance and templates related to clinical investigation, the EU’s Medical Device Coordination Group (MDCG) guidance on clinical evaluation for medical devices has yet to be published.

Currently, the available guidance brings manufacturers no closer to an understanding of sufficient clinical evidence. Nonetheless, if the manufacturer implements key procedures at the outset of the clinical data collection process this confusion as well as other errors could be avoided.

These key procedures are:

  • Creation of a robust document and record control procedure. Ensuring changes to clinical documentation are approved and recorded to ensure the history for the study are captured and traceable. Helping Notified Bodies understand why decisions were made is crucial for successful document assessment.
  • A robust quality control procedure. Ensuring all device indications are represented in the study by applying scientifically sound methodology and capturing the appropriate type of clinical data for each. Clearly highlighting each indication and what clinical data has been collected within the clinical study report will help the Notified Body understand this document and how the data covers all device indications.

Consideration for who the ‘customers’ are for the Clinical Study Report (patient, healthcare practitioner and the Notified Body assessor) and anticipating the information they require will help avoid certain questions and nonconformities. Engagement with an experienced Contract Research Organisation who understands the requirements and the needs of the other stakeholders can ensure that the clinical evidence gathered is sufficient. On-hand experience of clinical data collection is paramount for manufacturers to avoid simple errors that carry significant impact at this pivotal stage of device development.

Overall, these procedures and considerations will help to prevent pitfalls of clinical data conformity in medical device trials. Addressing these challenges will ensure that the tightening of clinical requirements under the EU Regulations does not need to lead to devices leaving the EU, but instead helps make devices safer, as intended.

 

Richard is a medical device quality and regulatory expert with a comprehensive background encompassing the utilisation, research and manufacturing of medical devices and in vitro diagnostics. Richard holds a master’s degree in medical law specialising in the Medical Device Regulations of the EU and the UK. Richard also holds a master’s degree in structural molecular biology specialising in protein-protein interactions. Richard’s professional journey has traversed roles with a legal manufacturer, consultancy positions and as part of a Notified Body as well as a 6-year tenure as lecturer on medical device regulations at Cambridge University. Bringing to the table over 15 years of experience in the medical device industry, Richard has expertise in quality management systems, risk management, regulatory compliance and clinical strategy development, working on devices such as drug delivery devices, optometric devices, combination products and a wide range of invitro diagnostics including companion diagnostics. He can be reached at Richard.Bassett@iconplc.com.

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