An important constituent of Post Market Surveillance (PMS), Post Market Clinical Follow Up (PMCF) is a continuous lifecycle process, wherein the device’s clinical evaluation is constantly updated, confirming its safety and clinical performance throughout its expected lifetime. Since the requirements are said to increase under the MDR, this would necessitate prudent, thorough planning by manufacturers preparing to certify or gain recertification under the new Regulation.
The MDCG’s Guidance document details the methods and procedures in a PMCF plan that should be set up by the manufacturer to proactively collect and assess clinical data of a CE marked medical device. Manufacturers should document the findings from the PMCF in a PMCF evaluation report which is a part of the clinical evaluation report and technical document. The Notified Body will assess the adequacy of the PMCF plan basis, the manufacturer’s procedures and documentation of the PMCF, as well as the justification in relation to non-performance of PMCF.
Through the PMCF, the manufacturer is expected to ensure continued acceptability of identified risks, identify previously unknown side-effects and monitor the identified side-effects and contraindications. Based on actual evidence collected, the manufacturer should identify and analyze emerging risks and ensure that the benefit-risk ratio continues to be in accord with MDR guidelines. Further, the PMCF aims to validate that the device is deployed correctly for the product’s intended use. The PMCF must also identify cases of possible systematic misuse or off-label use of the device.
Key points to be covered
Manufacturers should describe the post-market activities that will be conducted , including the procedures corresponding to the specific product, the aim and the rationale for each activity described as being appropriate to achieve the required objectives. Some commonly used PMCF methods would include collecting data in registries, screening of scientific literature and other sources of clinical data, post-market studies, and patient and health care professional surveys.
At the outset, one must define the need for conducting a particular PMCF activity, with a note on where the need is coming from, such as a Notified Body, as a part of PMS, CER, Risk Management etc. For each activity, a description defining the aim(s), the rationale for choice of different procedures/methods should be given along with justifications for study design, sample size,timelines, inclusion/exclusion criteria and endpoints.Single N case studies can be appropriate when the more useful double blind, randomized studies do not exist. An in-depth literature research is required to justify the comparator, the basis of the intended purpose and the state of the art. It should also list timelines for each of the aforementioned activities (e.g. quarterly, annually) and the known limitations of the planned activities( e.g. incomplete follow up, missing data and so on). An important consideration here is that statistical justifications should be provided, as appropriate,for the expected outcomes, rationalizing why this is satisfactory in light of the residual risks.
A few common examples of key PMCF activities:
- PMCF studies: Manufacturers should provide a summary of the planned studies in line with the requirements above. For example, the PMCF study could contain details on extended follow up of patients included in the pre-market clinical investigations, new clinical investigations within the intended use, as well as retrospective, historic studies. Ethics Committees (ECs) approvals are required for PMCF studies. Any number of medical ethics and even general ethics texts are available. Citing one and detailing general conformance with key tenets may provide the reviewers a level of confidence in those preparing the PMCF.
- Manufacturer device registry: Depending on the type of medical device or the specific group the device belongs to, such a registry can be provided with a description and a summary of the plan. Based on the device and accessories, the quality and quantity of data to be collected and analyzed, specific protocols to be followed should be specified. In case appropriate national public registries with clinical data on the manufacturer’s own device and/or on similar devices can be utilized, it should be specified here.
- Planned Real-world evidence (RWE) analyses : The scope is to conduct analyses based on real world data collected in line with the requirements above. Needless to say, the real-world data should be from reliable sources and of sufficient quality. Often such evidence appears by reference or in summary form in sales literature and can shorten research times in locating appropriate findings and their publication.
- Manufacturers could choose to include surveys planned from health care professionals and/or patients which will gather information on the usage of the device under evaluation.
Assessing clinical data pertaining to equivalent or similar devices
Here the literature search again plays a major role, as clinical data pertaining to equivalent or similar devices may be used to update the information regarding the state of the art or to further evaluate safety outcomes, which can be presented in the PMCF report. The equivalent devices selected should be consistent throughout the technical documentation. One must indicate whether the selected device is demonstrated to be equivalent or is a similar device. However, in order to demonstrate safety & effectiveness of the device under evaluation, PMCF data collected only from this device can be considered. Again, a quick review of pertinent sales literature often can be surprisingly helpful.
Assessing the resulting impact on the technical documentation
Relevant clinical information from the Clinical Evaluation Report (CER) and Risk Management file must be followed up, analyzed and evaluated in the PMCF phase. The resulting impact after aggregating data from each PMCF activity of the device being evaluated, and the results from similar or equivalent devices which affect the technical documentation should be presented here. If not, the manufacturer must state that the clinical evaluation report and/or from the risk management file does not contain any relevant clinical information to be considered in this plan and the specific reason(s) for the omission. Last, but not the least, manufacturers must elucidate whether the collected clinical data from the device under evaluation still conforms to applied common specifications and/or applied harmonized standards, and/or guidance listed in the PMCF plan.
A prerequisite for effective planning, budgeting, and seamless execution of PMCF activities is an in-depth understanding of its constituents as well as its regulatory requirements, with relevant linkages to CER, risk management files and Periodic Safety Update Report (PSUR), the Summary of Safety and Clinical Performance (SSCP where applicable). A thorough, comprehensive and complete presentation of post market clinical data in an organized format will not only enable notified bodies and competent authorities to find the information they need quickly, but will also ensure safe and effective medical devices in the market, reducing risk of recalls and scandals. And finally, a well organized, well referenced and cleanly presented PMCF can enhance the reviewer’s confidence in the overall skills and competence of the applicant.