Dealing with adverse and serious adverse events in clinical investigations

In clinical investigations 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 unborn babies.

Careful monitoring and reporting are legal requirements that the sponsor of the clinical investigation must fulfil and provide additional protection and safety for all involved, including participants, users and others.

‍Definition of adverse and serious adverse events

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

An "adverse event" (AE) is therefore a negative medical incident, an unexpected illness or injury or negative clinical symptoms in persons participating in a clinical study who use the investigational medical device, even if they are not directly related to the investigational device.

A "serious adverse event" (SAE) is an adverse event that resulted in any of the following:

a) Death,

b) a serious deterioration in the health of study participants that resulted in any of the following:

(i) life-threatening illness or injury,

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

iii) hospitalisation or prolongation of hospitalisation,

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 foetus or congenital physical or mental impairments or birth defects.

In Germany

Documentation and reporting obligation

In accordance with Art. 80 of (EU) 2017/745 (MDR) in conjunction with and in Germany 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 fully recorded. This also includes all serious adverse events as well as device deficiencies that could have led to serious adverse events under unfavourable conditions. In addition, new findings on these events must be reported. Principal investigators and investigators must immediately report any serious adverse event and device deficiencies that could have led to serious adverse events even under less favourable circumstances.

The sponsor shall immediately report any serious adverse event potentially related to the investigational medical device and device deficiencies that could have led to such events to the Member States in which the clinical investigation is conducted. This notification shall be made via the electronic system referred to in Article 73 and shall include any new findings on these events.

With the exception of so-called other clinical investigations or clinical investigations after placing on the market(in accordance with Article 47 (3) MPDG), the reporting and notification obligations (Article 64 MPDG) must be reported electronically to the competent higher federal authority depending on the severity, the possible causal connection with the investigational medical device or an element of the clinical investigation, or with a device deficiency.

The reporting obligations and deadlines depend on the requirements of the European Medical Device Coordination Group (MDCG) in the guidance document MDCG 2020-10/1 Rev 1, the "Guidance on safety reporting in clinical investigations" in the current version.

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

For more information or an initial non-binding discussion , please contact us.