Writing the PMCF plan

A PMCF plan sets out which clinical data a manufacturer will collect on a marketed device, by which methods, to what end and on what schedule. Every device needs one, including a device whose plan concludes that no specific PMCF activity is needed at present.

When a plan is needed

A PMCF plan is required for all devices under the MDR, regardless of the device classification or the market history. ^{1, 2} One plan can cover more than one device, for example devices that belong to one device family or several devices with a similar intended purpose. ¹

The need for specific PMCF activities derives from the clinical evaluation report, the risk management or post-market surveillance. ¹ Reasons that might trigger it are, for example, trending in complaint data, or a clinical evaluation report that concludes there are insufficient data for specific product sizes or configurations or for a specific patient population. ^{1, 3} A plan can also conclude that there is at present no need for specific PMCF activities. ^{1, 2}

The first step in planning PMCF activities is to identify any gaps in the clinical evidence of the device. ⁴ The clinical evaluation should analyse whether all claims are supported, and where they are not, the PMCF plan describes how the identified gaps can be closed, which might involve gathering clinical data. ⁴

The plan among the device's documents

The PMCF plan is part of the post-market surveillance plan and of the clinical evaluation plan. ⁵ It is prepared during the development of the device together with the clinical evaluation plan, summarised in the initial clinical evaluation report, and submitted as part of the technical documentation for conformity assessment. ⁶ The notified body scrutinises the plan and determines whether sufficient clinical data already exist and whether the proposed plan will address any identified gaps in clinical evidence. ⁶ Once the device is CE-marked, the PMCF findings are analysed and presented in the PMCF evaluation report. ⁶ The plan should be reviewed and updated as part of the clinical evaluation of the device. ⁶

The aims of the plan

Under Annex XIV Part B of the MDR, the PMCF plan specifies methods and procedures for proactively collecting and evaluating clinical data with the aim of: ^{6, 7}

• confirming the safety and performance of the device, including the clinical benefit where applicable, throughout its expected lifetime ^{8, 9, 7, 5}
• identifying previously unknown side effects and monitoring the identified side effects and contraindications ^{9, 6, 5}
• identifying and analysing emergent risks on the basis of factual evidence ^{9, 6, 5}
• ensuring the continued acceptability of the benefit-risk ratio, in accordance with Annex I of the MDR ^{9, 6, 5}
• identifying possible systematic misuse or off-label use of the device ^{9, 7, 5}
• verifying that the intended purpose of the device is correct ^{9, 5}

The required contents

Annex XIV Part B also specifies the required contents of the PMCF plan: ⁷

• the general methods and procedures of PMCF to be applied, such as the gathering of clinical experience gained, feedback from users, and screening of scientific literature and other sources of clinical data ⁶
• the specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies ⁶
• a rationale for the appropriateness of those general and specific methods and procedures ^{6, 10}
• a reference to the relevant parts of the clinical evaluation report and to the risk management ^{6, 11, 12}
• the specific objectives to be addressed by the PMCF ^{6, 13}
• an evaluation of the clinical data relating to equivalent or similar devices ⁶
• a reference to any relevant common specifications, harmonised standards when used by the manufacturer, and relevant guidance on PMCF ^{6, 14, 12}
• a detailed and adequately justified time schedule for the PMCF activities to be undertaken by the manufacturer, such as analysis of PMCF data and reporting ^{6, 14}

The time schedule covers the frequency of review, a statement of how and when the PMCF data will be analysed and reported, and a time schedule for the PMCF report. ¹⁴

General and specific methods

A PMCF plan should include both general and specific methods of PMCF. ⁹ Sources draw the line between the two differently, in particular for literature reviews and surveys. ^{15, 16, 17}

In one account, the general methods are the data sources to be analysed, followed up and evaluated according to the plan: usually the clinical evaluation report, the risk management report, possibly the risk-benefit analysis, and the post-market surveillance report. ^{9, 15} For these data sources the plan should give the frequency of review and their output, meaning whether any of the documents concluded that there is an actual need for PMCF now. ¹⁵ The same account counts among the specific methods a proactive clinical literature review, a customer survey of healthcare professionals or of patients depending on the device, enhanced complaint and adverse event monitoring, company-sponsored studies or registries, and use of a public registry to collect PMCF data. ^{15, 10}

In another account, the general methods include literature reviews, looking at publications, general use feedback and reporting, and surveys, and the specific methods include clinical investigations, registries, investigator-initiated studies and high-quality PMCF surveys. ^{16, 17} General methods usually take less time, effort and cost, but because they are more general, the level of evidence they give is lower. ¹⁷ Specific methods give a much higher and more reliable level of evidence, and their time, effort and cost are likely to be higher too. ¹⁷

The methods a plan can draw on include:

• screening of the scientific literature or other sources of published or clinical data ^{18, 13}
• post-market studies, such as prospective case series, retrospective patient record reviews or nested registry studies ^{18, 13}
• data from public or manufacturer-initiated registries ^{18, 19, 13}
• surveys of healthcare professionals, patients or users, depending on the device ^{19, 13}
• reviews of case reports that may reveal misuse or off-label use of the device ^{19, 13}
• enhanced complaint monitoring ¹⁹

Literature screening is one of the easiest methods of collecting clinical data. ⁴ The plan can also outline the collection of clinical data related to equivalent or similar devices. ¹⁴

Choosing and justifying the methods

The rationale for the appropriateness of the methods can be based, for example, on the device classification, since an implantable or Class III device may need more effort on PMCF activities than a Class I device, on whether the device is a legacy product with a long unremarkable market history or a new device, and on the clinical data available so far. ¹⁰ The choice of methodology should be based on the level of risk associated with the device. ¹³ For example, literature screening might be a sufficient PMCF activity for low-risk, non-implantable devices with sufficient clinical evidence. ¹³

How many ways of collecting PMCF data a notified body requires depends on the notified body, and one experienced writer holds that it also depends on the device classification, with Class III or implantable devices possibly needing more PMCF activities. ^{20, 21} A plan with a really good rationale for the appropriateness of its activity does not, in one experienced writer's view, have to list several activities. ²² It can focus on one PMCF activity, describe it very well, and decide once its results are in whether more PMCF activities are needed. ²² Where a PMCF study is planned, nothing else should be planned alongside it, because a study requires a lot of time and resources and should be sufficient. ²¹

The rationale for a PMCF study usually depends on the device and its classification. ²³ PMCF studies are usually used to collect data on, for example, implantable devices. ²⁴ One experienced writer holds that a good rationale for a study on such devices could be that long-term or longer follow-up data are needed, which only a study or perhaps a registry can collect, and a customer survey or a literature review cannot. ²⁴ For a lower-classification device, for example one used as an accessory, the plan can argue that no clinical study is needed, and feedback from users on how the device works and on any complications they experienced may be sufficient. ^{24, 25}

Objectives and detail

The objectives of the PMCF activities should be based on predefined safety and performance measurements specific to the device. ¹¹ The objective of a literature review could be a search for new articles relevant to the safety and performance of the device, or to identify off-label use or unknown risks. ¹¹ A survey has to address feedback on the safety and performance criteria of the device, and it can also seek information on potential off-label use, ask users whether the instructions for use are readable, understandable and still valid, or gather information on any device failures. ^{11, 14} The objective of a registry or a clinical study could be to confirm the safety and performance of the device throughout its expected lifetime and to identify unknown risks and side effects. ¹⁴ Where the plan uses literature screening, it should include a specific and objective research question and a detailed literature search protocol. ⁴

Common PMCF pitfalls are having no PMCF plan at all, not producing the PMCF report in due time, and plans and reports that are not detailed enough. ^{2, 26} To give enough detail, the plan has to identify the objective of each PMCF activity clearly: what is to be measured, what is to be searched for, and why the method is appropriate for the device. ²⁶ It always has to provide a statistical rationale, which can sometimes be really complicated, and a clear timeline. ²⁶

The MDCG plan template

Guidance on how to set out the PMCF plan is given in MDCG 2020-7. ⁵ In April 2020 the Medical Device Coordination Group (MDCG) published and endorsed a PMCF plan template, together with a PMCF evaluation report template, as guidance for manufacturers to ensure compliance with the relevant requirements. ^{3, 13}

Annex XIV Part B of the MDR provides the minimum requirements for a PMCF plan, but its description is rather short and lacks detailed information, and uncertainties exist about which information has to be documented and how. ¹³ The MDCG templates give detailed instructions on format and content to guide manufacturers in complying with the MDR. ^{13, 7} They are not European Commission documents and are not legally binding. ¹³ They were designed to simplify the work both of the manufacturer, in complying with all relevant standards, and of the notified bodies or competent authorities, in extracting data. ¹³ Manufacturers who have already prepared their own PMCF plan templates might need to update them to capture any elements missing from the MDCG guidance. ¹³

The PMCF plan and the PMCF evaluation report are similar in content and section structure, and both templates have seven sections. ¹³ Both documents shall be stand-alone documents, and therefore the manufacturer details and the device description and specification need to be documented in the first two sections. ¹³ The sections of the plan template are:

• A. Manufacturer contact details, the general data about the manufacturer ^{27, 13, 3}
• B. Medical device description and specification, including a general device description, the intended purpose, the intended users and target population, indications and contraindications, and warnings and precautions; any variants or configurations of the device and any accessories used in combination with it, with whether they are covered by this plan or by a separate one; and the device classification ^{27, 13, 3, 28}
• C. Activities related to PMCF: general and specific methods and procedures ^{27, 13, 28}
• D. Reference to the relevant parts of the technical documentation ^{27, 13, 29}
• E. Evaluation of clinical data relating to equivalent or similar devices ^{27, 13, 29}
• F. Reference to any applicable common specifications, harmonised standards or applicable guidance documents ^{27, 13, 29}
• G. Estimated date of the PMCF evaluation report ^{27, 13, 29}

Section C describes each PMCF method and procedure in detail in a subsection of its own, which gives:

• where the need for the PMCF activity comes from, whether the clinical evaluation report, post-market surveillance or the risk management documentation ^{12, 28}
• a description of the activity, and whether it is a general or a specific method or procedure ^{12, 13, 28}
• a definition of the aim of the activity ^{13, 28}
• a description of its methods ^{13, 28}
• a rationale for the appropriateness of the chosen methods and procedures, which includes and is not limited to justifications for sample size, endpoints, comparators, study design or statistics ^{13, 28}
• a detailed and adequately justified time schedule for all planned PMCF activities ^{13, 28}

The plan must document the evaluation of the clinical data related to equivalent or similar devices as defined in the clinical evaluation plan. ¹² The template states that clinical data from equivalent devices are not suitable to demonstrate the continued safety and performance of a device, but they may be used to confirm or update the state of the art and to identify relevant safety outcomes, and the device under evaluation itself should deliver the data that demonstrate its continuing safety and performance. ^{29, 12}

Contributors to the plan

Finalising a PMCF plan needs a lot of input from different departments. ²⁹ The clinical affairs team usually plans and conducts the PMCF activities. ³⁰ The regulatory affairs department may be needed for common specifications, standards and guidance. ³⁰ Quality is usually the department that handles PMCF plans and reports and establishes the risk management documentation. ³⁰ Where clinical studies are involved, the clinical development department may need to be contacted, and legal compliance or marketing may be needed as well. ³⁰

Medical writers prepare PMCF plans and reports together with clinical operations, who oversee clinical investigations and device registries, and with the post-market surveillance, regulatory and quality assurance groups. ³¹ Medical writers are increasingly involved in writing PMCF plans and, in due course, PMCF evaluation reports. ⁷

Consulting the notified body

One experienced writer holds that the notified body is not really allowed to hint at or say which PMCF activities a manufacturer should carry out. ³² Contacting the notified body about planned PMCF activities can still help avoid planning, for example, a study where results from a survey would be sufficient for the notified body. ³² Where there is the chance, the manufacturer should try to contact the notified body and discuss the plans, to get at least an impression of what it expects to be done as PMCF. ^{21, 22, 32}