The International Medical Device Regulators Forum (IMDRF), a voluntary association of medical device regulating authorities collaborating on the improvement of the legislative framework has published a position paper describing the proposed approach to the post-market clinical follow-up studies. The document has been published in the course of public consultations. The IMDRF will accept comments and suggestions from the industry representatives until December 11, 2020.
Basic Concepts and Regulatory Background
The IMDRF acknowledges the importance of the clinical evidence used in the course of medical device safety and performance evaluation carried out during the premarket stage. At the same time, the association states that the scope of the information available before the device is being used is quite limited. For instance, premarket clinical investigations are usually limited in time, while the actual scope of such studies is also limited. In some cases, the clinical data deriving from comparable devices already placed on the market do not cover all the important points.
According to the general rule, and the medical device placed on the market should comply with the Essential Principles outlining the main safety and performance aspects, including a favorable risk/benefit ratio. At the same time, in some cases, it is almost impossible to identify all safety-related issues during the premarket clinical investigations due to the limitations mentioned hereinabove. For example, it is quite difficult to evaluate the long-term performance of the device or some rare adverse events during the limited time premarket investigation. Hence, according to the IMDRF, these aspects should be properly addressed in the post-market clinical follow-up (PMCF) which should be more rigorous and detailed. However, it is also mentioned that in any case such studies should not be construed as the replacement for the premarket data to be provided in the course of initial review of the device to be carried out before it would be made available to the customers.
PMCF Studies: Key Points
The post-market clinical follow-up studies constitute one of the most important elements of a post-market surveillance program. The present IMDRF position paper describes the association’s current thinking on the proposed way PMCF studies should be designed, implemented, and used. In particular, the scope of the guidelines contained in the document covers the following aspects:
- The circumstances where a PMCF study is indicated;
- The general principles of PMCF studies involving medical devices;
- The design and implementation of PMCF studies; and
- The use of information from PMCF studies.
The document also contains references to the applicable IMDRF guidance documents on clinical evidence, clinical evaluation, and clinical investigation, and also to the applicable international standards, including ISO 14155:2020 Clinical investigation of medical devices for human subjects, Good clinical practice; and ISO 14971:2019 Medical devices – Application of risk management to medical devices.
It is also important to mention that in vitro diagnostic medical devices are actually falling outside the scope of the guidance.
Terms and Definitions
In order to introduce additional legal clarity, the IMDRF also provides the definitions of the most important terms used in the context of the post-market clinical follow-up studies. The definitions provided in the IMDRF position paper on PMCF include, inter alia, the following ones:
- Post-market clinical follow-up study – a study carried out following marketing authorization intended to answer specific questions (uncertainties) relating to safety, clinical performance, and/or effectiveness of a device when used in accordance with its approved labeling.
- Clinical evaluation – a set of ongoing activities that use scientifically sound methods for the assessment and analysis of clinical data to verify the safety, clinical performance, and/or effectiveness of the medical device when used as intended by the manufacturer.
Besides the aforementioned terms, the document also defines the clinical evidence as the clinical data related to the medical device in question and evaluation of such data; and also the clinical investigation – as a special study conducted with the involvement of the patients to assess the safety and performance of a medical device.
Post-Market Clinical Follow-Up Studies Application Cases
The IMDRF also describes in detail the particular situations when the post-market clinical follow-up studies should be applied. As was already mentioned before, upon completion of the premarket assessment of a medical device some safety-related aspects could still remain unclear. According to the document, PMCF studies should be carried out in order to obtain additional information and collect clinical data to cover the aforementioned information gaps. The association also mentions that sometimes PMCF studies should be also necessary to investigate adverse event trends or other information deriving from adverse event reports related to the medical device already placed on the market and allowed for use by healthcare professionals and customers. According to the document, PMCF studies are intended to address the uncertainties that may exist, namely:
- Long-term safety, clinical performance, and/or effectiveness aspects, which could not be fully evaluated during the premarket assessment of a medical device. In such cases, a few years needed to collect sufficient data. This point also covers the aspects associated with adverse events and compatibility issues identified in the course of post-market surveillance activities.
- Novel technologies or new intended use. In case if the technologies the medical device is based on are entirely new, additional time is needed to collect sufficient information on the actual performance and risks associated thereto. The same approach should be applied in case of new indications for use or patient population.
- Higher-risk devices and use scenarios. In case if the use of the medical device is associated with a relatively high risk, additional data should be collected.
- Generalizing clinical investigation results.
- The approval granted to the medical device is actually based on the clinical data associated with a similar (comparable) medical device already placed on the market. In certain cases, this could be sufficient for granting the initial marketing approval, while the more detailed device-specific data should be collected by the virtue of PMCF studies.
- New information related to the safety and performance of a medical device already placed on the market.
- Placing the medical device on the market under the simplified and accelerated procedure (e.g. in case of a public health emergency).
- Rare anticipated adverse events.
- The actual effectiveness of the measures taken to mitigate known safety-related risks.
However, PMCF studies are not mandatory for all medical devices. According to the approach suggested by the IMDRF, they should be applied in case when additional information is necessary to assess the aspects associated with the safety, clinical performance, and effectiveness of the medical device.
The IMRDF position paper also outlines the core elements of a PMCF study. According to the document, a post-market clinical follow-up study should contain the following elements:
- Study objectives which should be clearly identified,
- Design of the study based on the scientific methods and approaches, and also described in the study plan,
- The actual implementation of the study in accordance with the initial plan and further interpretation of its results to get a reasonable conclusion.
Summarizing the information provided here above, the IMDRF position paper on post-market clinical follow-up studies describes the approach proposed by the association with regard to the most important aspects associated with the PMCF studies to be carried out in order to collect additional safety-related information.
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