PMCF activities

What is the goal of your PMCF activities?

To confirm the safety and performance throughout the expected lifetime of your medical device or IVD, this includes:

Identifying previously unknown side effects
Monitoring identified side effects and contraindications
Identifying and analysing emerging risk
Ensuring the continued acceptability if the benefit risk ration
Identifying possible systemic misuse or off-label use.

The data generated through the selected PMCF activities will inform your Post Market Surveillance (PMS) and your Clinical Evaluation Report (CER)/Performance Evaluation report (PER).

Your Post Market Clinical Follow-up Plan should include both general and specfic activities with a clear goal for these activities. What data are you looking to generate? Are the methods appropriate?

To answer these questions, you need to consider the varied options of PMCF activity.

General PMCF activities

General activities are INFORMATION GATHERING in nature – often general subjective data, which by themselves do not provide a manufacturer with robust scientific evidence to demonstrate safety and performance. They should be used in conjunction with specific activities.

These methods are often subject to bias and variability across sources.

Some of the key challenges:

Literature review – limited data on the product under review, poor quality of the literature. There is also considerations to be had around the use of equivalent devices and the literature published on that devices. If equivalence is to be used, there must be a clear demonstration of equivalence – please review MDCG 2020-5 and get in touch if in doubt.

Access to patients and users: do you have adequate access, consent and data protection in place?

Specific PMCF Activities

Specific methods are exactly that – more specific and more tailored to generating a scientifically significant dataset. They have a more defined purpose, population and defined dataset – if well done, these activities will provide you with the raw data on your product to support the demonstration of safety and performance.

Whatever activities are chosen, the PMCF Plan must have a clear justification for the choice.

PMCF Studies: often considered the gold standard, these can come in all shapes and sizes:

Randomised control trials
Prospective controlled study/expansion of the pre- market clinical investigation

Retrospective study
Systematic review- Meta analysis
Observational studies
Registry studies

Note: they are considered mandatory for products that:

Gained their CE mark based on equivalence
Are a novel technology
Longer term safety and performance is not known
Used in a high-risk population

These studies should have defined protocols – setting out as a minimum: defined population & sample size, inclusion and exclusion criteria, appropriate objectives & endpoints and follow-up.

There may be a need for ethical and competent authority approvals.

A PMCF study, as with a pre-clinical study, should be in-line with the expectations of ISO 14155:2020

Challenges:

Inadequate or unjustified design.
Additional cost

Longer timelines for data generation
Gaining approvals

Registries: This could be a product specific registry or a bigger product type registry – again either across a smaller population or area or indeed national such as the National Joint Registry.

A well designed and well used registry can be a great source of raw data for your product. A full analysis has the protetnial to product scientifical valid data around safety and performance.

Challenges:

To set and operate can be costly.

Limited reach – gaining patient and healthcare professional input can be challenging as often not possible to mandate.

Larger more national/global registries may only hold limited relevant data for the purpose of PMCF. Considerations should always be given to the utility of the data.

Patient surveys: These are probably the most utilised tool seen at the moment.

Surveys offer a degree of flexibility, they can be general but also designed to be highly specific – they can meet a wide range of needs in data generation.

General surveys tend to be retrospective design – asking the end-user to recall information on the device and its use.

Specific surveys can be patient level and case specific – this can be a single survey or a series of surveys that follow the usage of the devices (prospective). This could be direct to the patient or via a healthcare professional using patient records. The data obtained from this type of activity will be of higher quality – usually producing clinical data on the devices under review via patient outcome data and clinical indication data.

They also are considered relatively easy to design and conduct.

However, they should be used appropriately and as with all the activities their use needs to be justified within the PMCF plan.

Challenges:

Access to the end-users – this can be limited /restricted e.g. if a distributor is used.
Bias – the structure of the survey is important in minimizing bias. More of a concern with subjective healthcare professional responses.
Lack of responses – the survey needs to be accessible and simple to complete. Users may get ‘fatigue’ in completing them if they are too long, too complicated or not relevant.
Loss of focus – as set out above the survey needs a clear direction – if too many objectives are attempted the survey may not be clear enough, and the data returned may be skewed.
GDPR compliance is critical

Ethical review and approval may be required – individual countries may have different requirements.
Investigator initiated studies: Often seen as another usful tool, as much of design and conduct of the study is lead by the third party. If designed well, this will of course be useful in generating data around safety and performance, howver, the ‘ownership’ sits else where and this can provide challenges.

Challenges:

- Limited control over conduct or data sets
- Potentially there may be extra cost if you chose and are able to take an active role.
- There is less assurance that you are getting the true data – the true picture of safety and performance.

Post Market Clinical Follow up Plan

Annex XIV Part B

6.2.  The PMCF plan shall include at least:

the general methods and procedures of the PMCF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of clinical data;

the specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies;

a rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);

a reference to the relevant parts of the clinical evaluation report referred to in Section 4 and to the risk management referred to in Section 3 of Annex I;

the specific objectives to be addressed by the PMCF;

 an evaluation of the clinical data relating to equivalent or similar devices;

 reference to any relevant CS, harmonised standards when used by the manufacturer, and relevant guidance on PMCF; and

a detailed and adequately justified time schedule for PMCF activities (e.g. analysis of PMCF data and reporting) to be undertaken by the manufacturer.

This is what is required as a MINIMUM. PMCF plans should be designed to product real world evidence on your device’s safety and performance under normal use. This is longitudinal data collection, providing evidence on the safety and performance for the lifetime of the product.

The plan needs to be detailed with clear justification for the activities chosen – how will they generate the data you are seeking to evaluate. What is relevant for your device!?

Use the PMCF plan template provided in MDCG 2020-7!

Post Market Clinical Follow up Report

MDCG 2020-8 provides guidance and a template for the report.

A PMCF report should:

Align with the PMCF plan
Set out what activities were conducted
Analyse the data generated from the PMCF activities
Document the results
Be part of the technical documentation

must be updated annually Class III and implantable devices.

Critical to remember that this report is taken in to consideration when updating the CER for your product. There are a number of considerations when reviewing the conclusions of the PMCF cycle.

Are updates to the IFUs required?
Does the risk management file need to be reviewed?

Is the labelling still accurate?
Should the indications for use be changed?
Are the contraindications still correct?
Are any formal corrective actions required?
Is there a need for any design or manufacturing changes?

This is a technical document and it should be clearly presented, and a scientifically robust conclusion with a focus on safety and performance of the product. It is a living document that needs to be updated and considered carefully.

If there are gaps – this often happens. If you discover ‘data gaps’ or a lack of demonstration in a particular area, then this needs to be reviews and evaluated. It should be demonstrated and be part of the conclusions. If it is a significant gap, then further activities may need to be considered and agreed on with you Notified Body (if relevant). Smaller gaps, maybe justified, but mitigations should be put in place to address them moving forward. Each circumstance is different, and the decision will need clear justification and be documented.

What is the Notified Body’s role?

There is a significant increase in scrutiny by the NB under the new regulations. There are key timepoints at which the NB is likely to review your PMCF plan and data:

During initial conformity assessment
If you submit a significant change review
Recertification
During review of an SSCP or your PSURs
Routine review – e.g. annually for class III and implantable products

Don’t forget the Competent Authorities can also request the data – it needs to be done and available as set out in the PMS plan.

This is not an exhaustive list – just the key points of review – again it is a demonstration of that ‘lifecycle’ approach and that consistent review across that lifecycle.

It is not just a box to tick – it is a critical function that will build the knowledge of your device, allowing for that reassurance that your product continues to perform and that the benefit risk ratio continues to be acceptable and risks are mitigated as far as possible.

Relevent guidance:

MDCG 2020-7 PMCF plan template: A guide for manufacturers and notified bodies

MDCG 2020-8 PMCF Evaluation Report: A guide for manufacturers and notified bodies

MDCG 2021-6 Q&A on clinical investigations

MEDDEV 2.12/2 – Post Market clinical follow up studies

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