Guidance document for the notification procedure for serious adverse events to MRECs

On October 1, 2015, an amendment to the Medical Research Involving Human Subjects Act (WMO) will come into force. This amendment concerns the requirement of reporting all serious adverse events (SAEs) to the reviewing medical research ethics committee (MREC or CCMO). It is possible to report SAEs in the form of periodic line-listings instead of individual reports within applicable legal timelines, or to refrain from SAE reporting. The procedure for SAE reporting and notification should be described in the research protocol and assessed by the reviewing MREC. In order to obtain uniformity in the assessment of this notification procedure the CCMO, together with the Dutch Association of Ethics Committees (NVMETC), has developed a guidance document for MRECs. This guidance document also contains information relevant for sponsors and investigators.

Guidance document for notification procedure SAEs to MRECs

The guidance document (dutch) will correspond as much as possible to already existing European legislation on the reporting of safety issues in clinical research. It is also aimed at minimising the administrative burden resulting from this WMO amendment for investigators, sponsors and MRECs. To this end four categories of research have been defined:

  1. Studies with investigational medicinal products, in accordance with EU Directive 2001/20 and the CT-3 guidance on the collection, verification and presentation of adverse event/reaction reports arising from clinical trials on medicinal products for human use.
  2. Research with medical devices that must be notified to the Health Inspectorate, i.e. non- CE marked medical devices or CE marked devices that are used outside the intended use(s) covered by the CE marking. For this, existing MEDDEV guidelines are used.
  3. Observational research in which subjects are only subjected to additional standard diagnostic procedures (such as blood sampling, standard physical examination, CT-scan, MRI). With this type of research the reporting of SAEs to the reviewing MREC will only be made compulsory if it is regarded to be of added value is with respect to subject safety.
  4. Other types of research, where a distinction is made between on the one hand, an SAE that is suspected to be related to study procedures and/or certain rules of behaviour which the subject has been imposed to and on the other hand, an SAE for which there is no such suspicion.

In the research protocol the procedure that describes when and which SAEs have to be reported and in which way (individual reporting, line-listings), has to be documented (see model onderzoeksprotocol versie oktober 2015). This procedure needs to assessed by the reviewing MREC. The MREC reserves the right to deviate from the categorisation as presented above. Considerations that may play a role are appointed in the guidance document.

Transitional provision and evaluation guidance document

From October 1, 2015, all new submissions have to meet the new WMO legislation for SAE reporting. For ongoing studies that were assessed before October 1, 2015, the possibility is offered to ensure that on December 31, 2015, at the latest, the information on the registration and reporting of SAEs is adapted by means of the submission of an amendment to the reviewing MREC.

After one year the guidance document will be evaluated.