Clinical evidence from clinical investigations outside the European Union

The MDR 2017/745 regulation on medical devices clearly specifies the requirements that clinical investigations must meet in order to be submitted as clinical evidence in the clinical evaluation that is drafted to obtain a CE marking. In particular, in its Chapter VI, it explains that the purpose of clinical investigations shall be to collect clinical data. These data shall be aimed at demonstrating the conformity of the products. It also lays down basic requirements concerning the ethical and scientific evaluation of clinical investigations of medical devices.

As the text makes clear, such research must beauthorised by an authoritative body in one of the EU member states.

Why is the approval of a member state important?

The MDR 2017/745 states that clinical investigations may be conducted only when a number of conditions are met, including the following:

The clinical investigation must be authorised by the Member State(s) in which it is to be conducted in accordance with this Regulation, unless otherwise provided for.

This insistence arises for two reasons: On the one hand there is the need to assess whether the investigations comply with the international standard ISO 14155, on the other to ensure that the extrapolation from the investigated population to the target population within Europe.

ISO 14155:2011, or its new harmonised version for the MDR, ISO 14155:2020

As stated in Article 64, the MDR states that:

Standards for clinical investigations should be in line with sound international guidelines in this area, such as the international standard ISO14155:2011., «Clinical investigation of medical devices for humans. Good clinical practice»

The fact that clinical research is conducted under the percepts of the ISO standard responds to the need to facilitate the acceptance of the results of clinical research carried out in the Union as documentation outside the Union. It also makes it easier for the results of clinical investigations conducted outside the Union to be accepted within the Union. In other words, that clinical research conducted outside the EU can be used as clinical evidence in a clinical evaluation.

It is up to the Member State where the clinical investigation is to be carried out to determine the appropriate authority to assess the application for a clinical investigation, in the case of Spain, the AEMPS.

Extrapolation of results; clinical evidence

On the other hand, it must be remembered that the CE marking is valid for marketing in Europe and it must be guaranteed that the results of these clinical research populations can be extrapolated to the European population. This is directly verified if clinical research is conducted on EU territory.

An example of the importance of extrapolating from clinical research populations is provided by the case of metamizole agranulocytosis in northern European populations. A few years ago, a study was published which concluded that “metamizole agranulocytosis is an adverse effect that occurs more frequently in the British and its use should be avoided”. This adverse effect is related to a genetic predisposition and has been known for a long time. This is why the ancestry of the patients to whom the medicine is administered must be taken into account. If clinical research is conducted in populations other than those in which it will be applied, genetically related side-effects may not be detected.

This does not mean that research conducted under the percepts of 14155 cannot be used as clinical evidence for clinical evaluation, only that the sample of the target population used in the research can be extrapolated to the EU target population. This can be demonstrated through anthropological or ancestry studies showing that the population broadly shares the European genome.

At Episkey Medical Consulting, we help medical device manufacturers to obtain authorisation for their clinical investigations by the AEMPS, as well as to demonstrate the clinical evidence of clinical investigations conducted outside the EU.




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