AEs are defined as any medically undesirable incident, unintended disease or injury, or aberrant clinical symptom (including atypical laboratory findings) in patients, users, or other subjects, regardless of their association with the investigational medical device. AEs may be reported by patients, prompted by the Investigator or designee, or collected through observation by the Investigator, the CEC, safety team or monitoring team. The Investigator will assess all AEs to determine their relation to the device and/or implant procedure and categorise them as related or unrelated to serious criteria based on their seriousness. In the event that an AE is deemed to have occurred, the Investigator must obtain all the information required to complete the AE form. Furthermore, it is of the utmost importance that patients contact both the investigator and/or the study coordinator should they encounter significant AEs occurring between scheduled study visits (box 3).

Serious adverse event (SAE)

An adverse event is deemed to be serious if the events are associated with

Death.

Serious health deterioration in the study patient, including life-threatening illness or injury, permanent impairment to body structure or function, prolonged hospitalisation or the need for medical or surgical intervention to prevent permanent impairment to body structure or function.

Fetal distress, fetal death, congenital abnormality or birth defect.

Medically significant incident.

Serious medical events not meeting the above criteria may still be SAEs if they endanger the patient and require immediate medical or surgical intervention to prevent one of the above outcomes.

Pre-existing medical conditions or symptoms reported before enrolment will not be recorded as an AE. Record an AE if the pre-existing condition or symptoms worsen due to the device, or if study symptoms are due to the device or trial-related procedure. Do not record death as an AE, but only as a consequence of another specific AE.

Anticipated adverse events

Anticipated adverse events (AEs) are defined as such events which have been identified as potentially occurring in connection with the investigational device or implant procedure.

Unanticipated adverse device effect

An unanticipated adverse device effect (UADE) is defined as any serious adverse effect on health or safety, or any life-threatening issue or fatality, caused by, or associated with, a device, if that effect, problem or death was not previously identified in the investigational plan or application (including a subsidiary plan or additional application) or any other unanticipated serious issue related to the rights, safety or welfare of subjects.

It is imperative that all UADEs are reported to CEC without delay. Completion of the AE Form of the CEC is also mandatory for all UADEs. In addition, the Investigator is obliged to inform his/her EC/IRB of all UADEs occurring at his/her site no later than 10 days after the Investigator first becomes aware of the effect (and any additional information as required by EC/IRB or local regulations).

All AEs associated with UADEs are subjected to close monitoring until either resolution or a stable clinical endpoint is achieved. Essential treatments and outcomes must be documented.