Undesirable events, such as serious adverse events (SAEs), may occur during the investigation. Also, a medical device deficiency may become apparent. These occurrences must be reported to the review committee in the form of safety reports. The procedures for safety reports are described in MDCG guidance 2020-10/1. The MDCG 2020-10/2 safety report form has been developed for reporting to the relevant committees. Each framework of clinical investigation under the MDR has different requirements for safety reporting.
No transitional arrangement has been established for safety reports of studies with a positive decision prior to 26 May 2021. This means that the safety reports of studies approved prior to 26 May 2021 and subject to MDR article 62 or article 74 must also fulfil the requirements of article 80. SAEs already reported through the MEDDEV 2.7/3 SAE report table do not need to be converted to the MDCG 2020-10/2 table. Exceptions are SAEs in studies that are just starting and SAEs with relevant new information on the report. This concerns only 'reportable events' (see flow chart Adverse events in research with medical devices) (link). For clinical investigations subject to MDR article 82, the rules of the Dutch Medical Research Involving Human Subjects Act [Wet medisch-wetenschappelijk onderzoek met mensen, WMO] continue to apply for reporting safety reports (article 10, WMO).
The flow chart below can be used for registering and reporting adverse events and medical devices deficiencies during clinical investigations.
Please note: The definitions of (serious) adverse events and device deficiency under MDR and WMO are different!
- Safety reports that must comply with MDR article 80 and MDCG 2020-10/1&2:
- Clinical investigations in the context of conformity purposes (MDR article 62 or 74.2);
- Post-market clinical follow-up investigations (MDR article 74.1) for SAEs related to the investigational procedure;
- Studies with a positive decision prior to 26 May 2021 and an obligation to notify the IGJ/CCMO, with the exception of studies that are subject to MDR article 82;
- Reporting is done using the MDCG 2020-10/2 table which is submitted via ToetsingOnline.
- Safety reports that must comply with the vigilance provisions of MDR articles 87-90 and that fall under the manufacturer's responsibility:
- Post-market clinical follow-up investigations (MDR Article 74.1) except SAEs related to the investigational procedure;
- Reporting of SAEs related to the investigational procedure is done using the MDCG 2020-10/2 table which is submitted through ToetsingOnline.
- Safety reports that must comply with article 10 of the WMO:
- Other clinical investigations (MDR article 82);
- Studies with a positive decision prior to 26 May 2021 and that are subject to MDR article 82;
- Reporting is done using the SAE report form on ToetsingOnline.
SAE is the abbreviation for Serious Adverse Event. An SAE is an adverse medical event in a patient or study subject that does not necessarily have a causal relationship with the treatment. The MDR uses the following definition:
Any adverse event that led to any of the following:
- serious deterioration in the health of the subject, that resulted in any of the following:
- life-threatening illness or injury,
- permanent impairment of a body structure or a body function,
- hospitalisation or prolongation of patient hospitalisation,
- medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,
- chronic disease,
- foetal distress, foetal death or a congenital physical or mental impairment or birth defect.
The MDR uses the following definition:
Any inadequacy in the identity, quality, durability, reliability, safety or performance of an investigational device, including malfunction, use errors or inadequacy in information supplied by the manufacturer.
The sponsor must report any deficiency in the device that could have led to a serious adverse event if appropriate action had not been taken, if it had not been intervened with, or if the conditions had been less favourable.
How to submit
Because Eudamed is not available as yet, the sponsor is required to upload the safety information through ToetsingOnline. The review committee will receive a message that the safety information (SAE, line listing) has been uploaded and can start the assessment. Safety reports of studies with a positive decision prior to 26 May 2021 and not subject to the Dutch Medical Research Involving Human Subjects Act [Wet medisch-wetenschappelijk onderzoek met mensen, WMO] may be reported at email@example.com. These should also be reported to the review committee.
Adjustment to the procedure for reporting adverse events and device deficiencies
You are required to inform the MREC concerned of the new procedure for registering and reporting adverse events and device deficiencies. This can be achieved through an appendix to the protocol. You do not need to submit a separate substantial amendment. You must incorporate the changes regarding safety reports in the next substantial amendment of the research protocol.