Post-Market Clinical Follow-Up plan (or a PMCF plan) must describe general and specific activities (or methods) that gather data on clinical performance and safety. Until now, there has been no guidance available for manufacturers on how to select the proper PMCF activities. This blog will supply an overview of both generic and specific PMCF activities, and guidance on when and how to include them in your PMCF plan.
Before the EU MDR, the number of proactive PMCF activities, such as PMCF studies, have been limited to higher risk devices. This is largely because existing EU medical device regulations and guidelines had loopholes which many medical device manufacturers took advantage of.
The MEDDEV guidance documents are a good example of this, where some of the reasons for not to conduct PMCF studies were largely misinterpreted by the industry and used as an excuse to not conduct PMCF activities.
Because PMCF requirements have not been as stringent as they are now under the EU MDR, many MedTech companies have been getting by with small or non-existing clinical operations teams. And those companies who have more established clinical operations, are more used to conducting traditional clinical investigations with traditional clinical data capture needs.
The lack of PMCF experience in combination with the lack of practical guidance from the EU commission has led to great confusion amongst industry peers on what activities to include in a PMCF plan for different types of medical devices.
Below, you will find a thorough guide on how to select the appropriate PMCF activity for your medical device. However, we always recommend that you get expert advice on how to collect and manage your PMCF data. Connect with us and let us show you how SMART-TRIAL can help.
The EU MDR clearly states that the goal of PMCF is to continuously gather clinical experience data on your device. Specifically, manufacturers must gather data on both clinical performance and safety, which shall be used to update the Post-Market Surveillance (PMS) and Clinical Evaluation Report (CER).
The PMCF plan is the recipe for how you intend to achieve this. In the PMCF plan, you need to document both general and specific PMCF methods to collect this information. And it’s not enough to just document which activities you will conduct, you must also justify why and to which degree they are relevant for your PMCF plan, with scientific reasoning.
But how does the EU MDR and the MDCG guidelines define general and specific PMCF activities?
General PMCF activities are information-gathering operations that often produce a subjective dataset, which cannot be used alone to scientifically document safety and clinical performance, to a level which is acceptable for continued marked approval.
These can be activities such as:
The last example, i.e. “other sources of clinical data” can in theory be anything, and its definition in the MDCG guidelines is absent. But in most cases, this is referring to other sources of data such as published data and research on similar (equivalent) devices. from similar marketed devices
General PMCF methods alone are not likely to provide sufficient data that can live up to standards needed to illustrate performance or safety. This is because the source of data is often subjective (i.e. not scientifically valid) and the quality of data can highly vary from one source to another. For example, it can be difficult to document clinical performance based on subjective surveys from physicians.
Which is why, for most devices, you often need to combine these activities with data from specific PMCF activities.
Specific PMCF activities are “higher-level” operations that can produce a dataset which can be used to scientifically illustrate safety and clinical performance, often based on case-specific data.
These can be activities such as:
All these examples are based on patient cases where the device is being applied in practice. This produces a dataset where scientific methods can be applied to document clinical performance and safety, to a standard that is accepted by the industry and clinical practice.
The biggest pros to using specific activities is the fact that you usually gain direct access to the raw data that’s captured, which can be difficult with more general activities. Such as with screening of scientific literature. This is important to note, because the EU MDR specifies that manufacturers must be able to show clear access to the data used for clinical evaluation or PMCF, when referring to clinical or safety data from equivalent devices (It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence).
But even though the regulation and the MDCG have provided some examples for general and specific activities. What are the actual PMCF activities that medical device manufacturers are including in current PMCF plans?
At SMART-TRIAL, we have had a chance to review and provide feedback on many PMCF plans. Looking back, we've come to realize that there’s a clear harmony between the various PMCF plans and the activities selected for data gathering.
Some of the most common activities seen to date are:
Each activity has its own set of pros and cons, and it's vital to evaluate each activity together with other factors involved before deciding on which activities to include in your PMCF plan. These factors include:
Medical Device classification and reporting requirements
Depending on the medical device class there might be shorter or longer time available to gather enough data for first PMCF report. This can highly impact which activity you select for your PMCF plan and how long you can conduct one to produce sufficient data.
Sales numbers and markets
If your sales are not high enough, it can be difficult to collect enough data from observational activities. Low sales will potentially require you to initiate interventional studies of some sort.
Data available from earlier Clinical Evaluations
Quality data from earlier clinical evaluations is the best indicator for the level of PMCF data needed for future activities. Depending on how much you need to “bridge” in terms of safety or performance, will impact the choice of PMCF activity selected for your PMCF plan.
Device performance measure and clinical/industry standards within the domain of interest
How is your device’s clinical performance measured? What data is required and from whom? Some activities might not fit your device, because the data originating from that activity might not suffice the standard required to document performance.
Whether you have access to customers
Do you know your customers well enough, and can you contact them directly for feedback and information? Or even collaboration? Having direct access to your customers can open the doors up for data collection activities, such as surveys.
Whether you have access to end-users
Do you know your end-users well enough to be able to contact them directly? Do they know your brand well enough for you to be able to gather survey data directly from them? Do you have their contact information, or is that blocked behind a distributor? If your answer to these questions is no, it might be difficult to gather survey-based data.
Whether you have access to the patients
Do you have consent to access data, or access to contact patients directly for patient-reported outcomes or feedback? Having data processing consents in place from patients already, is crucial to ensure compliance. You need to ensure that patients have provided consent to process their data, if you get access to a public data registry.
How the device is used/applied in practice
How is your device applied in practice? Does it always require intervention/control of clinical experts? If yes, you might not have a possibility to gather data from others than patients.
Whether there’s a data consent in place (from existing data sources)
For those existing registries or data sources that contain relevant data for PMCF, do you have applicable consents in place to gain access to these databases?
In combination with the deciding factors above, it is important to consider the pros and cons of each available PMCF data collection method before moving forward with the PMCF plan. In the following, we have assembled the key pros and cons for each method to simplify medical device manufacturers' decision on which PMCF activity to use.
Literature and research publications are still a valid method of gathering information on clinical performance and safety. Even though the EU MDR might have drastically changed the way we approach clinical evaluation, there is nothing in the regulation that states that references to the literature and published material on devices cannot be used for PMCF.
Compared to many other PMCF activities, literature search requires less resources and is simple to complete. This is also why many manufacturers have relied on publications on similar devices (equivalent devices) for clinical evaluation.
Certain types and families of devices are more common (or popular) than others when it comes to research, which means that there might already be a vast amount of information available on safety and performance on equivalent devices in the literature.
There is still one big issue with using literature for clinical evaluation and PMCF, especially when referring to equivalent devices. As stated in the EU MDR Annex XIV:
„It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence. “
In short, manufacturers need to have access to the data used for clinical evaluation reporting - which also includes PMCF. This can be difficult to demonstrate without having contracts in place with the authors of publications or other manufacturers.
Third-party registries are databases that private/public organizations, institutions or governmental bodies have established for various reasons. Some of these registries contain valuable information on the application and clinical outcomes of medical devices in practice.
Registries are common for high-risk devices (Class III) and long-term implantable devices, and often contain detailed information on each case/patient. Registries for lower class devices are also found, but these are far less common and often only established for research purposes with funding from grants etc.
Data from a third-party registry is usually centered around patients or cases, which provides a sufficient level of traceability and detail needed for PMCF. The fact that datasets are already available means that manufacturers will not have to initiate new activities to collect the same data. Using registries can be less expensive than initiating new and private device registries.
Registries do not exist for every single device in every country. The need and requirements for these registries can be vastly different from one country to another, and the data quality can equally vary. Some registries might be held to a high standard while others are updated less frequently. The data in these registries might be relevant but may not contain the exact attributes needed to document/demonstrate clinical performance for a given device.
Lastly, GDPR data processing consents collected from data subjects in these registries might lack the necessary legal grounds to allow manufacturers to access the data.
Investigator initiated studies (IIS) have become increasingly more popular among medical device manufacturers to gather clinical data. Some larger manufacturers have dozens and even hundreds of key opinion leaders who are continuously running clinical investigations on medical devices, which the manufacturer somewhat sponsors. In return, manufacturers gain access to use the data for regulatory and marketing purposes. Learn how to use investigator initiated studies to generate MDR compliant data here.
IIS have the potential to collect vast amount of subject-specific data and outcomes. Because they are investigator initiated, they are managed in full by the investigator staff, which also means that much of the operational expense is covered by the investigator site and team. Some of these IIS are partly sponsored by the manufacturer, by providing devices or other resources, but much of the cost, planning and management is covered by the investigator. The data coming from these kinds of studies can be highly valuable, and the cost-benefit of conducting investigator initiated studies for regulatory activities can be highly positive.
The quality of IIS varies quite a lot. It can be difficult to ensure that IIS are following standards, such as ISO 14155:2020, which is the golden standard for conducting investigations with medical devices. This might require more resources from the manufacturer than anticipated, and thus increase the cost. At the same time, because the IIS is managed by the investigator, it can be difficult to influence the research goal and type of data collected. As such, the data collected might not be as relevant for PMCF reporting as needed.
PMCF Surveys is a hot topic in the MedTech industry, as many medical device manufacturers look to implement surveys in their PMCF plans to address the PMCF MDR requirements. A survey is just one way of collecting data, and is usually accomplished by asking a set of questions to a certain group of individuals who share a common attribute.
Surveys can be initiated in multiple ways, with various tools, and for PMCF these can either be directed towards end-users (like patients) or physicians. Depending on who the recipient is, the data can either be subjective or patient-specific. Learn how to design a successful PMCF survey here.
Conducting a Survey may not require as many resources as a clinical investigation or IIS. By having access to either end-users or physicians who use the device in practice, it can be fairly easy to initiate a survey and ask a few questions on performance or safety. Sending out a survey does not necessarily require approvals from ethics committees (although this differs from country to country) and responding to a survey does not have to take much time either. Thus, this can be a quick and easy way to gather data for all parties.
No matter what kind of survey you plan to initiate, it will require access to end-users (physicians or patients) who represent a valid sample of the population using the device in practice. This alone can be a challenge for many, as devices are often sold through distributors who cannot provide information on the end-users to the manufacturer.
Even though surveying patients can provide valuable information on outcomes and safety, this might not be relevant for all devices, which means that surveying physicians is the only option. It can be difficult to structure a survey to request subject-specific data from physicians without it becoming subjective. When a physician is answering a survey, questions are usually generic and do not refer to a specific case. Thus, results from a survey like that will not provide scientifically valid datasets to illustrate performance.
SMART-TRIAL Survey was engineered to simplify PMCF surveys for medical device manufacturers. The goal was to make PMCF Surveys under MDR a viable PMCF data collection method for any type of medical device. Read more about SMART-TRIAL Survey here.
A PMCF Cohort Study or Survey is a data collection activity minded primarily towards patients. This kind of activity is usually completed over 2 or more time points, where data is collected from patients in an observational manner (e.g., via surveys and questionnaires).
Asking patients directly about clinical outcomes and safety provides scientifically valid data that can be used for PMCF. Conducting a cohort study might not be as expensive as conducting an investigation, but it can still provide a similar level of data quality (depending on the design). If a cohort can be initiated before and after receiving a device, this can provide even better evidence on both safety and performance, instead of only asking patients who have been using the device before.
Similar to surveys, a Cohort study would require contact or access to patients, either directly from manufacturer to end-users or via healthcare experts. At the same time, a cohort study is also only relevant if the device outcome measures are based on patient-reported outcomes. If performance is not based on patient-reported outcomes, a cohort study might be deemed irrelevant for PMCF.
PMCF Case series is a simple data collection activity that includes a series of cases or patients. For years, device manufacturers and device sales reps have gathered basic data from physicians (often in paper-based manner) to document effects and use of the device across different cases. This can be used for post-market surveillance, and for better understanding of how the device is applied in practice. Now, with digital solutions becoming the golden standard for clinical data collection for MedTech, it might become easier for manufacturers to initiate case series to gather data for PMCF. For example, this can be done by enabling physicians to report simple data in an ad-hoc manner on every 10 or 100 cases.
When established, Case series do not require much work from Manufacturer and can provide a continuous and valid source of patient specific data, without much interference to standard practice. This is also a very cheap alternative to investigations.
For higher class devices it can prove difficult to setup case series data collection when long-term follow up is needed on detailed clinical outcomes. Case series are often more applicable for simple datasets over short periods of time. In addition, this requires access to physicians and other key opinion leaders, as well as motivational incentives designed to drive continued data collection.
SMART-TRIAL Cases was specifically designed for this purpose, to replace old-fashioned paper-based case-series forms with a GCP compliant digital solution.
PMCF studies or post-market investigations (both observational and interventional) are still some of the most popular sources of data when it comes to PMCF. PMCF studies can be of different types and depending on different factors mentioned above (such as previous gap analysis, sales numbers and more). These can be either of observational or interventional nature. The biggest difference between the two, is the level of planning and regulatory documentation needed. Manufacturers that have enough devices in use in practice, can look to initiate observational investigations – sometimes also called PMCF registries.
By including a PMCF study in your PMCF plan, you can be almost certain that the data quality is good enough for the Notified Body. On top of that, you can be in full control of what data is collected and how you would like to use it.
The data quality and control come at a cost of additional resources. Furthermore, for some devices that require long-term follow-ups, it can take years to gather sufficient data on performance and safety, to be able to use the data from a PMCF study for PMCF reporting. Until then, PMCF reports should be supported with other activities.
SMART-TRIAL Suite is the ideal data collection tool when running a PMCF study or investigation. This enables seamless integration of eCRF and ePRO, which streamlines and simplifies the entire study design. Read more about SMART-TRIAL Suite here.
There is no one activity more correct than the others. Each PMCF plan must take all of these (and more) into account and evaluate the pros and cons together with other factors that can impact the decision.
Knowing the available PMCF activities as well as which data collection tool is best suited for each activity, is very helpful in the PMCF planning process. To get a better understanding of the digital data collection tools that SMART-TRIAL offers for PMCF, you should take a look at our services overview.
If you're interested in learning more, see our complete guide on how to ensure compliant Post-Market Clinical Follow-up data collection under the EU MDR.