The medXteam GmbH blog series now begins with an overview of the different types of clinical trials that are possible for medical devices. These will then be described in more detail in the following episodes.

Types of clinical trials involving medical devices

1 Introduction

EU Regulation 2017/745 (Medical Device Regulation, MDR) emphasizes the need for medical device manufacturers to systematically collect and evaluate clinical data before and after approval of their products. Many manufacturers are unaware of the importance of clinical data in demonstrating the compliance of their products. This affects both the approval of the products and the “post-market activities”, in particular the “post-market clinical follow-up”.

In Article 2 (48) “Definitions” the MDR defines the term “clinical data” in more detail:

"Clinical data means information about safety or performance obtained during the use of a product from the following sources:

• clinical trial(s) of the product in question,

• clinical trial(s) or other studies reported in the scientific literature on a product whose similarity to the product in question can be demonstrated,

• in peer-reviewed scientific literature published reports of other clinical experience either with the device in question or with a device whose similarity to the device in question can be demonstrated,

• clinically relevant information from post-marketing surveillance, in particular from post-marketing clinical follow-up."

The MDR cites clinical trials as the first source. These will therefore continue to play an important role in the future. The following definition can also be found in the MDR:

"Clinical trial" refers to a systematic investigation involving one or more human participants, conducted to evaluate the safety or performance of a product.

(Source: MDR, Article 2, Paragraph 45)

2. Types of clinical trials

All clinical studies with medical devices are clinical trials.

A distinction is made between the following types:

• Basic research - other clinical trials (MDR Article 82)
• Pilot study/approval study: clinical trials to demonstrate the conformity of products (MDR Article 62)
• PMCF study: clinical trials related to products bearing the CE marking (MDR Article 74)

In addition, there is now the so-called DiGA study specifically in Germany:

• Study with a digital health application ( DiGA ) to demonstrate positive care effects to achieve reimbursement status.
• d. R. with CE marked medical device: PMCF study
• If planned into the approval process, an approval study is also possible

(Sources: DiGAV, DVG, DiGA guidelines)

 

Figure 1: Different types of clinical trials

These different types differ in terms of the respective regulatory requirements, the approval procedures at the higher federal authority (BOB) and the Ethics Commission (EK) and the timing of implementation. This is briefly presented in the following subsections.

2.1 Clinical trials to demonstrate product conformity

The clinical investigation to demonstrate the conformity of products is the classic registration study. It is regulated in Article 62 of the MDR and, with regard to national requirements for its commencement and significant changes and corrective actions, also in Section 2 of the MPEUAnpG, and in particular in Subsection 1 in Sections 31 to 46.

Table 1: Objectives and timing of clinical trials to demonstrate product conformity

2.2 PMCF studies

Table 2: Objectives and timing of clinical trials related to products bearing the CE mark

Some PMCF studies are regulated in Article 74 of the MDR and are clinical investigations conducted with a CE-marked product: clinical investigations relating to products bearing the CE marking. However, Article 74 of the MDR only covers two specific cases of such PMCF studies: those involving additional burdensome investigations (Article 74(1)) and those conducted outside the intended purpose of the medical device (Article 74(2)). 

PMCF studies within the intended purpose and without additional burdensome examinations are regulated nationally.

2.3 Other clinical trials

Other clinical investigations are regulated in Article 82 of the MDR and in Chapter 4, Subsection 2, Sections 47 to 61 of the MPEUAnpG (Medical Devices EU Adaptation Act).

In Section 3 Sentence 4 of the MPEUAnpG it is defined as follows:

"[...] a clinical trial that

a) is not part of a systematic and planned process for product development or product monitoring by a current or future manufacturer,

b) is not carried out with the aim of demonstrating the conformity of a product with the requirements of Regulation (EU) 2017/745,

c) serves to answer scientific or other questions and

d) takes place outside of a clinical development plan in accordance with Annex XIV Part A Number 1 Letter a of Regulation (EU) 2017/745."

Table 3: Aims and timing of other clinical trials

2.4 DiGA studies

The area of ​​DiGA studies (studies for digital health applications - DiGA) is a national special case.

According to the Digital Healthcare Act (DVG), insured persons in the statutory health insurance system are entitled to receive DiGA (Digital Health Applications), which can be prescribed by doctors and psychotherapists and are then reimbursed by the health insurance company.

A prerequisite for this is that the digital health application (DiGA) has successfully completed a review process at the Federal Institute for Drugs and Medical Devices (BfArM) and is listed in a directory for these reimbursable digital health applications (DiGA directory). According to the DiGA Ordinance (DiGAV), a positive healthcare effect must be demonstrated in a controlled study to include a DiGA in the DiGA directory . This study is generally conducted with a CE-marked product. However, it can also be conducted as part of the approval process, in which case it must meet the requirements for such a study as outlined in the DiGA guidelines .

2.5 Outlook

In the next blog post, we will first discuss in detail the "Other clinical trials" now regulated by the MDR. 

3. How we can help you

At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.

Do you already have some initial questions?

You can get a free initial consultation here: Free initial consultation