The Art and Science of Successful PMCF Planning

• Recognise the strategic importance of PMCF planning. PMCF plans under MDR will be required for the entire lifecycle for each of your products. It’s an ongoing activity vital to the continued commercial viability of your portfolio and therefore needs to be regarded as a core business process. Blindingly obvious, perhaps, but a point worth making. From the outset you should be thinking about PMCF planning across all products. Which elements of your plan can be generalized into a template and reused for all similar products and across different markets?  Where are the pinch points that require product or market-specific customisation? To what degree can you generalize safety and efficacy questions for product classes, and can you develop metrics that will have widespread applicability across different markets?
• Leverage equivalence with your own products. A natural corollary to the first point. This should be a fundamental consideration in your PMCF planning strategy (claiming equivalence with devices from other manufacturers is now extremely difficult under MDR).
• Ensure PMCF planning is a multi-stakeholder process. Make sure that all key internal stakeholders in the business are fully engaged so that the resource demands and potential impacts of the PMCF plan are fully understood and signed off before submission. For example, detailed timelines are required now under MDR; certifying bodies may well suspend certification if data collection activities are not completed within the period specified in the plan.  Marketing insight and understanding of how devices are used, emerging industry trends, who the key opinion leaders and main competitors are, and the financial landscape you operate in should not be underestimated when it comes to developing your wider PMCF objectives.
• Go Digital. As you build your strategic long-term PMCF platform, it surely makes sense to digitise now. The rate of uptake of EDC in pharma/biotech has exploded in recent years and you’d be hard put to find a company that wishes it hadn’t made the transition. The amount of data you will be expected to provide is set for exponential growth in the years to come – paper and spreadsheets will be simply to way too onerous and expensive to maintain. It’s not simply the cost benefit equation to consider, it’s also about data completeness and real-time access. EDC properly implemented is a recognized as an important component of Good Clinical Practice and is important to being able to demonstrate transparency and control to the Notified Body.
• Be strategic, accurate and transparent in all communications with your Notified Body. It’s very important that you deliver on all the PMCF activities you cite in your plan. If you fail to deliver on specific activities because they turned out to be too expensive, for example, it will be a hard fight to convince the NB that the activity is NOT required. Importantly, this can also impact on subsequent submissions for other, similar devices. It’s possible, perhaps even likely, that there will be an expectation that later submissions should reflect a commitment to the same evidential standard as described in the original submission.
• Be aware that Ethics approvals may often be required for PMCF activities that are not GCP studies or RCTs. Rules and expectations differ from country to country as to what sort of activities require formal ethical approval or simply notification. The application and approval process can sometimes be time consuming which in turn could have a major negative impact on your plans if the time taken to achieve approval has been underestimated or not factored in. Before any submission is made to the Notified Body, it’s essential that you investigate the approval requirements as set-out by each ethics body on a country-by-country basis. By and large they are easy to communicate with and have a lot of information on their websites. The costs are not onerous when set against the costs of potential delay and, typically, if a formal approval is required, it will usually take 1 to 3 months to be confirmed.
• Be data driven; it’s important to establish what type of data needs to be collected FIRST. Specifically, you need to identify where the gaps are in your data that support the claims you are making. What hypothesis are you seeking to prove? What table or graph do you want to produce? Be clear about this. Once your data requirements have been properly and accurately established, it will be easier to define and design the specific type of PMCF activities needed to deliver that data. Proposing changes to the methodology during data collection is at best a fraught and time-consuming process which will not sit well with the Notified Body.
• Collect the ONLY data you need. The more data you ask for the more likely you are to have to contend with missing data, or worse, poor response rates which can cause significant delays and, at wort, failure of compliance. Not only that, but the more data you collect, the higher your costs will be. Ethics committees will closely scrutinise the nature of the data you are collecting, and approval may be withheld, causing costly delays.
• Ensure that your sample size is scientifically calculated and clinically justified. Acceptable biostatistical methods will need to be augmented with further justification based on the type of the study to be undertaken (e.g., looking to demonstrate equivalence or superiority?) and underlying clinical assumptions such as the baseline historic expectation of clinical efficacy or what the minimum clinical effect is to be demonstrated in the specific activity. The guidance leaves manufacturers with considerable latitude when it comes to justifying the sample size and thorough literature search is a good place to start.
• Follow closely the advice in ISO 14155:2020 Clinical investigation of medical devices for human subjects — Good clinical practice as they apply to your chosen activities. The 2020 iteration of the ISO standard now has a new annexe -annexe I – with suggested study designs appropriate to the life cycle stage of a device. It also explains which part of the standard are not applicable to PMCF. There is much more clarity now about how to apply GCP to the different types of study design appropriate to PMCF. Following these guidelines faithfully will minimise any necessary rework and avoidable delay. Again, it goes without saying that if you lack the expertise and experience in operationalizing this standard, it will pay to seek professional advice. Finally, it’s worth noting that some Notified Bodies have already said that they will not consider clinical data UNLESS GCP has been demonstrably observed.
• Ensure that your data collection tools are fully and correctly validated. This is a GCP stipulation. Simply put it means that the specific software you intend to deploy for data collection has been rigorously tested prior to release to production to eliminate bugs that could generate data errors.
• Gets to grips with – but do not fear – GDPR. No-one should underestimate the complexities of GDPR and the dangers that failure to comply entail. Despite the long-standing joke that no two GDPR experts ever seem to agree, the quality of advice and guidance has improved significantly over the last couple of years. By ensuring that the needs of GDPR underpin all study or trial design considerations from the outset, achieving confirmation of GDPR compliance should not cause undue delay. Again, if in doubt, seek professional advice – there’s no shortage nowadays! From the perspective of choice an EDC system as your PMCF platform, it’s essential to check that all physical and logical security systems comply with GDPR requirements, and that data is encrypted both in transit and at rest to the necessary standard.
• Don’t be overly dependent on input from Key Opinion Leaders. PMCF under MDR is set to generate a huge number of requests for data and participation in PMCF studies at clinics and hospitals across Europe. You will need to ensure that you are able to call upon physicians and centres beyond your KOLs not only to ensure that you can generate the data you need but also to demonstrate to the Notified Body that you are not relying only on feedback from a small number of friendly physicians. The opinions of physicians outside of the more academic environment (where KOLs tend to aggregate) could be vital to securing continued market access. After all, these physicians are likely to be far more time pressured and unlikely to be able to spend time experimenting with the best way to optimise the clinical value of your product.
• Design a single database as a repository for all data generated by your PMCF activities – this will simplify and accelerate the production of your PMCF evaluation report
• Plan to leverage the commercial benefits of PMCF. Whilst it’s unarguable that for very many companies PMCF will certainly mean increased costs and often the need to secure additional (and scarce) expertise, the information gathered will be invaluable for product improvement, messaging, and future innovation. Another important reason for involving product development, marketing, and sales in your PMCF team.