And what if something doesn't go as planned? Dealing with adverse and serious adverse events in clinical trials

In clinical trials with medical devices, it is important to closely monitor, document and report adverse events such as medical problems or injuries in all participants. These events can be serious, such as death, life-threatening illness or permanent physical injury. They can also have an impact on the fetus.

Careful monitoring and reporting are legal requirements that the sponsor of the clinical trial must fulfill and provide additional protection and assurance to all involved, including participants, users and others.

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Regulation (EU) 2017/745 (MDR) defines adverse and serious adverse events (Art. 2, (57 and 58)).

An "adverse event" (AE) is a negative medical occurrence, unexpected illness or injury, or negative clinical symptoms in subjects participating in a clinical trial who use the investigational product, even if not directly related to the investigational product.

A "serious adverse event" (SAE) is an adverse event that had one of the following effects:

a) Death,

b) a serious deterioration in the state of health of study participants that led to one of the following consequences:

i) life-threatening illness or injury,

ii) permanent physical injury or permanent impairment of a bodily function,

iii) inpatient treatment or extension of the inpatient stay,

iv) medical or surgical intervention to prevent a life-threatening illness or injury or to prevent permanent physical damage or impairment,

v) chronic illness,

c) Endangerment of the unborn child, death of the fetus or congenital physical or mental impairments or birth defects.

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In accordance with Art. 80 of (EU) 2017/745 (MDR) in conjunction with Section 64 (1) of the Medical Device Law Implementation Act (MPDG), all adverse events identified in the clinical investigation plan as important for the evaluation of the study results must be recorded in full. This also includes all serious adverse events as well as product deficiencies that could have led to serious adverse events under unfavorable conditions. In addition, new findings regarding these events must be reported. The sponsor shall immediately report all serious adverse events potentially related to the investigational device and device deficiencies that could have led to such events to the Member States in which the clinical investigation is being conducted. Such reporting shall be made via the electronic system referred to in Article 73 and shall include any new findings relating to such events.

With the exception of so-called other clinical trials or clinical trials after placing on the market(according to § 47 (3) MPDG), the reporting and notification obligations (§ 64 MPDG) must be reported electronically to the competent higher federal authority depending on the severity, the possible causal relationship with the investigational device or an element from the clinical trial, or with a product defect. The reporting obligations and deadlines depend on the requirements of the European MDCG 2020-10/1 Rev 1, the "Guidance on safety reporting in clinical investigations" of the Medical Device Coordination Group (MDCG) in its current version.

The forms for this can be found on the website of the Federal Ministry for Drugs and Medical Devices (BfArM).

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