Clinical evaluation is a lifecycle process, not a one-time activity
Insights from a Let's Talk Risk! conversation with Sarah Panten
Note: this article highlights key insights gained from a conversation with Sarah Panten as part of the Let’s Talk Risk! with Dr. Naveen Agarwal series on LinkedIn. Listen to the full recording of the discussion below.
The current medical device regulation in the European Union (EU-MDR) includes the terms clinical evaluation more than 140 times! Articles 61-82 in Chapter VI outline extensive requirements for clinical evaluations and clinical investigations. Additional requirements for clinical evaluation, post-market clinical follow up (PMCF) and clinical investigations are outlined in Annex XIV and Annex XV respectively.
Clearly, clinical evaluation is now more important than ever under EU-MDR (and IVDR). As a result, a general feeling in the medical device industry is that it is now significantly more challenging to bring innovative new devices to market. The burden of proof on manufacturers to demonstrate compliance with safety and performance requirements through clinical evidence is very high.
Clinical evaluation is the process of gathering (clinical) evidence to demonstrate that a medical device meets the safety and performance requirements. Without clinical data, there is practically no chance that a medical device will be granted marketing authorization in the EU. Therefore, it is very important to plan your activities for generating clinical data early.
That is why Sarah emphasizes the need for good planning early in the product development process. Clinical evaluation should not be treated as an afterthought, a last minute check-the-box activity required for marketing authorization by regulatory authorities. Clinical evaluation involves a review and analysis of different types of data sources which are typically generated by different processes. These include design and development, risk management, post-market and clinical investigations.
In practice, these processes are managed in separate workstreams by different functions within a company. There is very little coordination and alignment, which leads to wasted effort and lost time when critical pieces of information need to be processed across different interfaces as part of generating the clinical evidence. As an example, it is not uncommon for the risk management process to deliver an Excel worksheet to the clinical evaluation team with hundreds, or even thousands, of line items corresponding to different types of risks. It becomes challenging to extract clinically relevant information from this type of data source.
Understanding the interface between clinical evaluation and risk management is important. The risk management process runs through the entire lifecycle of a medical device, starting from design and development, to production and post-production. Since a medical device is expected to remain safe and effective throughout its lifecycle, the clinical evaluation process is also a lifecycle process. It is not a standalone, one-time activity. Therefore, there should be a tight integration between risk management and clinical evaluation.
In the rapidly changing regulatory environment, Sarah advises practitioners to work collaboratively, share ideas and best practices. We don’t have to wait for another guidance to be released. We can connect with each other, start a conversation and learn together. This is how we can continue to help bring new innovative medical devices to market quickly.
Here are a few key points that emerged from our discussion:
Clear definition of benefits is an important part of clinical evaluation: the main purpose of clinical evaluation is to support the claim of safety and effectiveness for a medical device. Safety and effectiveness is evaluated in the context of the benefits of the intended use and the overall residual risk. The 2019 revision of ISO 14971 now includes a formal definition of the term benefit to highlight this key point. Therefore, it is very important to clearly define the (clinical) benefits of a medical device early in the design and development process to help plan and integrate clinical activities with product development activities.
Benefit-risk evaluation is relative to the state of the art (SoTA): benefit-risk of a medical device is not an absolute measure; rather it is evaluated relative to the corresponding state of the art. Although the phrase state of the art is also defined in ISO 14971, it is generally not understood well in the industry. In practical terms, there are two components to SoTA - medical state of the art, and technical state of the art. We have to look at both aspects when evaluating our medical device in comparison to alternative treatments available in the market for a similar intended use. It is also important to define roles and responsibilities related to gathering information about SoTA.
There is a need to define and better understand clinical risks : the term risk can be interpreted differently under different circumstances. Clinical evaluation involves analyzing clinical data to verify the safety and performance of a medical device in the context of its intended use. Failure analysis from an engineering perspective, on the other hand, involves identifying and controlling failure risks to achieve high reliability. Not all risks, therefore, directly relate to the clinical experience with a device. In light of the increased regulatory focus on clinical evaluation, practitioners are now talking about the need to define and better understand clinical risks. A working group is currently developing a new international standard, ISO/AWI 18969, on clinical evaluation of medical devices that includes this topic.
Post-market surveillance is an active process of information collection and review : the requirement of a systematic process of actively collecting and reviewing safety-related information in clause 10.1 of ISO 14971 is a recognition of this emerging expectation of global regulatory authorities for post-market surveillance. It is not sufficient to simply monitor trends in the complaints and adverse events data. Rather, we have to actively gather information from different sources such as scientific/medical literature, conferences, customers, key opinion leaders etc. We may also need to conduct additional clinical investigations to continually update our clinical evaluation to reflect the latest clinical experience in the post-market phase.
Industry collaboration is now more important than ever : the global regulatory environment is changing fast. The new EU-MDR, as noted above, has a heavy emphasis on safety and performance in the clinical context. The US FDA is also working on harmonizing the Quality System Regulation (QSR) with the requirements of ISO 13485:2016, which has a lot more focus on risk. Technology is also evolving rapidly with new applications of artificial intelligence and machine learning (AI/ML) in medical devices. In this dynamic environment, it is more important than ever for risk practitioners to collaborate across national boundaries. It is only through such collaboration and exchange of ideas that we can develop a better, more practical knowledge of emerging technology and regulatory requirements.
About Sarah Panten
Sarah Panten is currently the Co-Founder and Managing Partner at avasis, which provides digitalization services to companies in the medical device and machinery industry. She has worked as a trainer and a consultant for more than 10 years at different organizations including TUV SUD and NSF. In 2014, she initiated the digitalization of the design control process at iThera Medical to manage complexity and traceability of information. Her current focus is to develop medical device specific software solutions based on the Siemens Polarion software platform to help companies efficiently implement regulatory requirements.
About Let’s Talk Risk! with Dr. Naveen Agarwal
Let’s Talk Risk! with Dr. Naveen Agarwal is a weekly live audio event on LinkedIn, where we talk about risk management related topics in a casual, informal way. Join us at 11:00 am EST every Friday on LinkedIn.
Disclaimer
Information and insights presented in this article are for educational purposes only. Views expressed by all speakers are their own and do not reflect those of their respective organizations.