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The European Medical Devices Regulation (EU MDR) is now in full effect (as of May 26, 2021), which impacts any medical device manufacturer with plans to get devices approved in the EU as well as manufacturers with existing products on the market.
Moving forward, requirements for medical device approvals for European healthcare will be following a more stringent but also far more standardized ruleset, as this is now an EU regulation, not only a directive, which was the case with the former EU MDD.
In particular, the EU MDR will increase the need for Post-Market Surveillance (PMS), and hereunder Post-Market Clinical Follow-up (or Post-Marketing Clinical Follow-up) (PMCF) as well as change the requirements for PMCF data. In most cases, medical device manufacturers will need to collect more clinical evidence for each medical device as well as improve the data quality and management.
This guide is the medical device manufacturer’s shortcut to best practices for any type of PMCF activities for medical devices. We have gathered everything you need to know in one place, and it includes:
1. Introduction to Post-Market Surveillance (PMS)
2. Why is Post-Market Surveillance Important?
3, Introduction to Post-Market Clinical Follow-up (PMCF)
4. Practical Guide to the Post-Market-Clinical Follow-up (PMCF) Plan under EU MDR
5. What You Should Know when Designing a Medical Device Post-Market Clinical Follow-up (PMCF) Plan
6. How to Select the Appropriate PMCF Activity for a Medical Device
7. How to Successfully Design a Post-Market Clinical Follow-up (PMCF) Survey
8. How to Calculate Sample Size for Medical Device Clinical Studies
9. How to Ensure Efficient and Compliant Adverse Event Reporting under MDR
Post-Market Surveillance (also called Post-Marketing Surveillance) (PMS) is an integral part of the regulatory framework of the EU MDR meant to ensure active and systematic post-market data gathering on all CE-marked medical devices.
This allows medical device manufacturers to continuously monitor product performance in real-world environments and thereby take corrective and preventive action (CAPA) based on ongoing risk management evaluations throughout product lifetime.
The purpose of PMS is to ultimately enhance patient safety by avoiding undetected defects or safety issues by ensuring active surveillance of actively used medical devices.
In the EU MDR, the definition of Post-Market Surveillance is:
'A proactive and systematic process which manufacturers implement and carry out (with other economic operators) in order to take corrective and preventive action (CAPA) in accordance with information on medical devices and their performance.' (MDR Art 2 (60))
From here on out, all medical device manufacturers are required to specify a thorough PMS plan for all CE-marked medical devices used in the European healthcare sector. The PMS plan must include:
What data to collect
How the data will be analyzed and which actions will be taken
Which PMCF methods and procedures will be used
Read more about Post-Market Surveillance under the EU MDR in chapter VII of the regulation. See the regulation document here.
The EU MDR has drastically increased the focus on clinical evidence and Post-Market Surveillance (PMS), but why has this become such an integral part of the new regulatory framework, and should medical device manufacturers embrace or question this change?
Historically, most medical devices in the EU and USA have been approved for healthcare by proving equivalence to an already legally marketed device. A process that has led to medical devices being approved based on already marketed devices with relatively dated original healthcare approvals.
Thus, the original predicate devices now have many offspring products, and these products may differ significantly in both design, look and materials. With the MDR, the EU has acknowledged that this process is prone to approving potentially unsafe medical devices for healthcare due to lack of clinical evidence in equivalence approvals.
Post-Market Surveillance under the EU MDR is designed to ensure intended medical device performance in real-world environments, and it's hard to argue with the fact that the equivalence rule could potentially result in the approval of faulty devices due to lack of clinical evidence.
However, the increased focus on PMS naturally increases the cost of research and development, which can be an obstacle for many medical device manufacturers with innovative and safe devices.
That's why Electronic Data Capture (EDC) providers must innovate their solutions in parallel with industry regulation developments - something many traditional providers have neglected, at great cost to medical device manufacturers.
The need for state-of-the-art, flexible and affordable data collection tools to collect post-market clinical data is vastly increasing, and the EDC industry must deliver. Read more about why Post-Market Surveillance is important right here.
In the EU MDR, Post-Market Clinical Follow-up (also called Post-Marketing Clinical Follow-up) (PMCF) is defined as:
'A continuous process that updates the clinical evaluation and that shall be addressed in the manufacturer’s post-market surveillance (PMS) plan.' (MDR Annex XIV(B))
In its essence, PMCF is a systematic collection of clinical data, documentation and evidence with the purpose of proactively uncovering important safety or performance issues in a CE-marked medical device and updating its clinical evaluation.
PMCF is one (important) component of the Post-Market Surveillance plan for medical devices, and supplements the existing pre-market clinical and non-clinical data. PMCF data must be documented in a PMCF evaluation report, which is part of the Clinical Evaluation Report (CER) and the technical documentation for the medical device.
PMCF activities should run on a continuous basis throughout the entire lifecycle of a medical device.
Identifying and investigating residual risks associated with use of the device
Contributing towards the update of Clinical Evaluation
Detecting any emerging risks and previously unknown side-effects
Confirming the overall safety and performance of the medical device in normal use
Identifying systematic misuse of the device and its impact on safety and performance
The manufacturer's PMCF activities must be documented in a Post-Market Clinical Follow-up Plan. See a practical PMCF plan guide and an example of a PMCF plan here.
Finally, PMCF results must be collected in a PMCF Evaluation Report, which forms part of the Medical Device Clinical Evaluation Report (CER).
As mentioned, after the expiration of the EU MDR deadline of May 26th, 2021, re-certification and/or introduction of new medical devices in European healthcare now requires a completely different approach to PMCF activities from medical device manufacturers.
But medical device manufacturers need guidance on how to build a PMCF plan after EU MDR, and how to leverage its advantages while avoiding compliance pitfalls. We will look closer at that below - visit our practical guide about how to handle the PMCF requirements of the EU MDR for a deeper and more thorough explanation of this issue.
The PMCF requirements of the EU MDR will increase medical device manufacturers' costs of conducting PMCF activities - that is an unavoidable fact. However, as PMCF activities become proactive and end-user transparency of medical device quality will increase, there are a number of potentially large advantages for manufacturers with high-quality medical devices.
The vastly increased amount and quality of data collected for each device will provide manufacturers with strong insights on their device performance which can be used in areas such as improved marketing of the device in question, or faster and more precise development of other medical devices based on learnings from the data.
To capitalize on these advantages, the manufacturers must handle data collection and management systematically and in a way that provides a complete overview of their PMCF data. Contact our PMCF experts to learn more about how to solve this with the SMART-TRIAL EDC platform.
Time-Consuming Ethical Approval
PMCF activities may need the approval of ethical committees, which can prove to be a time-consuming task, as ethical committees often require a formal application. Increased cost from this step is often a surprise for medical devices companies with limited PMCF experience.
GDPR must be taken into account when designing the PMCF plan, and in general when conducting clinical studies. This is a step that can seem daunting, but the obstacle may not be as comprehensive as many believe.
The key to GDPR compliance lies in utilizing systems that guarantee the correct data security measures as well as obtain clear informed consent from data subjects. Learn more about specific implications of the GDPR on Medical Device clinical activities and PMCF here.
Missing Key Opinion Leaders
The number of requests sent to clinical staff around Europe will only increase in the coming years, so it's imperative that you maintain a network of clinical experts that work with your device to ensure availability of users and avoid unnecessary PMCF study delays.
Learn more about the PMCF Plan pitfalls here.
Due to the stringent requirements of the EU MDR, getting all necessary elements correctly implemented in the PMCF plan can be a challenge. According to Part B of Annex XIV of the EU MDR, the PMCF plan must at least include the following:
The general methods and procedures of the post-market clinical follow-up to be applied
The specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or clinical studies
A rationale for the appropriateness of the methods and procedures mentioned above
Reference to clinical investigation report and risk management
The specific objectives to be addressed by the post-market clinical follow-up
An evaluation of the clinical data relating to equivalent or similar devices
Reference to any relevant CS (common specifications), harmonized standards when used by the manufacturer, and relevant guidance on PMCF
A detailed and adequately justified time schedule for PMCF activities
To simplify this, we suggest following this guide for any PMCF plan:
Start at the end and seek inspiration, start by defining what data you need to present, before you decide on the PMCF activity.
Don't forget the commercial side, your sales & marketing teams will benefit from your PMCF data.
Create a list of everyone involved in your PMCF activities and register what motivates these individuals to provide you with what you need.
Have a single database. This will save time in preparation for your PMCF evaluation report.
Remember that in-fact less data is more. At a later stage, you can change questions and parameters to monitor.
Make a PMCF plan template that is reusable across products and markets
Download our Whitepaper 'How to tackle PMCF for your Medical Device under the MDR' here. This includes a deeper explanation of each step as well as important insights on how to handle the PMCF plan under the EU MDR.
Before deciding on the PMCF plan strategy, the medical device manufacturer must consider a number of key points to ensure best practice and simplest way forward.
In short, the following points must be considered:
Can you claim product equivalence with one of your own existing products and avoid another PMCF study?
Can you statistically justify the reason for your specific PMCF data?
Are you following ISO14155 GCP and are your data collection tools validated?
Are you relying too much on KOL?
Be thoughtful in messaging to the Notified Body to avoid issues with unfulfilled promises of specific PMCF activities
For a thorough explanation of each point, watch our webinar on what you should know when designing a medical device PMCF plan here.
As mentioned above, the PMCF plan must describe the methods applied to gather data on clinical performance and safety. Selecting the appropriate PMCF method for a medical device under the EU MDR has proven to be a difficult task for many medical device manufacturers, as there is currently a significant lack of guidance available.
According to the MDR, the PMCF plan must include general and specific methods used, which must be justified with scientific reasoning, but at this point in time there's no practical guidance available from MDCG on how to address this.
So, to help medical device manufacturers select the appropriate PMCF activity, we have developed a guide that provides an overview of both general and specific PMCF activities, as well as how and when to include them in the PMCF plan. See the full Guide to Post-Market Clinical Follow-Up (PMCF) Activities here.
The most commonly used PMCF data gathering methods can be seen in this overview:
Image 1 - The most common data collection methods used by medical device companies to gather PMCF data.
Each PMCF method has specific strengths and weaknesses, and its usability will depend on a number of deciding factors. It is essential to thoroughly evaluate these factors before deciding on which PMCF activity to move forward with. The most prominent deciding factors are:
Medical Device classification and PMS reporting requirements
Sales numbers and markets
Data available from earlier Clinical Evaluations (gap analysis)
Device performance measure and clinical/industry standards within the domain of interest
Whether you have access to customers
Whether you have access to end-users
Whether you have access to the patients
How the device is used/applied in practice
Whether there’s a data consent in place (from existing data sources)
The Guide to Post-Market Clinical Follow-Up (PMCF) Activities includes an in-depth walkthrough of the deciding factors, as well as insights on pros and cons of each PMCF method.
A PMCF survey is one of the tools medical device manufacturers can choose to use in their PMCF plan to collect post-market data. However, as with most areas of Post-Market Surveillance, the requirements for PMCF surveys have changed after the implementation of the EU MDR. To successfully conduct a PMCF survey and pass the scrutiny of Notified Bodies, the sponsor must ensure that data gathering follows best practices. In particular, there are four key areas to keep in mind when designing the PMCF survey:
Select a tool that provides multiple ways to initiate surveys
A PMCF survey can be a less costly alternative to conducting a clinical investigation, but it also has its limitations and must be conducted correctly to avoid delays, added costs or ultimately loss of CE-marking.
The use of non-validated data collection tools can cause issues for medical device manufacturers, as Notified Bodies can claim that the data collection does not fulfill ISO14155 requirements on electronic data capture, which can render the collected data unusable.
We strongly recommend that any sponsor planning to run a PMCF survey consults their selected EDC provider and ensures full ISO14155 compliance.
See the full guide on how to successfully conduct PMCF surveys here.
For answers to some of the most frequently asked questions about PMCF surveys, watch our leading clinical data collection experts in this Q&A webinar on PMCF surveys from the MedTech industry.
The webinar covers questions such as:
Is PMCF required for all device classes?
What is the appropriate Sample Size for a Survey - especially if it covers 'lifetime' of a device?
Do you need to follow ISO 14155 when doing observational study using PMCF survey?
Watch the full PMCF Surveys Q&A webinar here.
Calculating sample size for medical devices can be a cumbersome and complex task and we see a continuously increasing number of requests for how to calculate sample size for specific medical device PMCF studies or which method to use.
To simplify this, we have created a number of practical tools that will help medical device manufacturers with sample size calculation and justification. You can get a detailed walkthrough of how to calculate sample size for medical device studies in our blog about sample size calculation.
Most medical device sample size calculations include five basic inputs. All five inputs are values that you must define or make assumptions on. The values will depend on the study objective, endpoints and design, and the sample size calculation will be very sensitive to the value inputs used, which makes the calculation prone to imprecision.
The five basic sample size calculation inputs are:
The minimal clinically meaningful effect
In addition to the basic inputs, three other factors should be taken into account:
Subject Drop-out rate
Download the Medical Device Sample Size Cookbook for a detailed explanation of the above as well as best practices for medical device sample size calculations. The cookbook also includes practical sample size calculation examples for medical device studies.
Sample size calculation should not be treated lightly, and we strongly recommend utilizing external assistance for guidance when possible. In collaboration with a biostatistician from Qserve, we have put together an informative webinar on the subject, which covers key areas of sample size calculation in clinical studies. You can watch it here.
Under MDR, both pre- and post-market clinical investigations must follow the latest requirements for GCP (Good Clinical Practice). Recording and reporting of adverse events (AE) and serious adverse events (SAE) is a key aspect of a successful clinical investigation and staying on top of regulatory changes is a must.
A common question that follows the MDR implementation is: Are There Differences in Reporting AEs in Clinical Investigations and PMCF Investigations Under the EU MDR?
The short answer is Yes!
However, it depends on whether the PMCF investigation is carried out on a CE marked device under its intended use or not.
If a device is CE marked and the investigation is observing outcomes under its intended use, the requirements for safety reporting are governed by MDR Article 80(5) and 80(6). This means that the provisions on vigilance in Articles 87 to 90 of the MDR apply instead of Article 80(1) to 80(4).
Therefore, manufacturers are only required to notify competent authorities of serious incidents that have not been thoroughly documented (known side-effects clearly described in the product documentation) prior to introducing the device to a market in the European Union.
Additionally, it is required to report safety corrective actions on devices used in third countries whenever the same device and configuration is in use in the EU.
All adverse events shall be reported in an interim or final report of a clinical investigation. So, regardless of an investigation being conducted pre- or post-market, the documentation requirements are the same.
However, keep in mind that national regulations may apply to requirements for reporting of adverse events during post-market clinical investigations. Medical device manufacturers must familiarize themselves with the specific requirements in each country.
We have an in-depth blog on the subject which will help you learn how to facilitate compliant AE/SAE reporting in clinical investigations under the EU MDR.
The blog discusses topics such as:
Adverse Event Reporting Requirements and Device Deficiencies That Could Lead to a Serious Adverse Event
Who is “responsible” for reporting Adverse Events to the authorities in Clinical Investigations?
Are There Differences in Reporting AEs in Clinical Investigations and PMCF Investigations Under the EU MDR?
Coding of Adverse Events for Medical Devices
Reporting Adverse Events in the absence of EUDAMED
How SMART-TRIAL Facilitates Adverse Event Reporting
Read the full blog on How to Ensure Efficient and Compliant Adverse Event Reporting under MDR here.
We offer unique MedTech experience and are always ready to help you simplify EU MDR compliance and reduce the workload. Medical device PMCF activities are as different as the devices are many and require extremely flexible Electronic Data Capture solutions, which is exactly what SMART-TRIAL is engineered to accommodate.
Get in touch if you need advice on your PMCF activities or want to know more about how SMART-TRIAL can help you.
We also offer a free product demonstration customized to your study needs, so you can see exactly how easy it is to simplify your clinical data gathering and management.
Jón Ingi Bergsteinsson, M.Sc. in Biomedical Engineering, is the founder and Director of EMEA Sales at SMART-TRIAL by Greenlight Guru, where he helps MedTech companies bridging the gap between their devices and clinical data. As the technical founder of SMART-TRIAL he previously served as the CTO where he paved the way...