Amendment WMO: reporting requirements serious adverse events (SAEs)

This autumn a modification of the Research Involving Human Subjects Act (WMO) will take place. This WMO amendment is applicable for all studies which are subject to the WMO. It concerns the requirement of reporting all SAEs, except for those that the protocol identifies as not requiring immediate reporting, to the sponsor and the reviewing medical  research ethics committee (MREC or CCMO).

On June 26, 2015 the WMO amendment is published in the Government Gazette (in Dutch). This amendment will come into force on October 1, 2015. The reason for this amendment was the investigation on the Propatria study (in Dutch) by the Dutch Health Inspectorate, the CCMO and the Food and Consumer Product Safety Authority. They concluded that the requirements for reporting SAEs in clinical trials other than clinical trials with an investigational medicinal product was not clearly enshrined in the WMO. This omission is repaired by the current WMO amendment. The Regulation for medical/scientific research with subjects (in Dutch), in which the notification procedure is stated, is also adjusted.

The most important changes are:

  • The investigator has to report all SAEs, except for those that the protocol identifies as not requiring immediate reporting, to the sponsor to the study.
  • The sponsor has to report these SAEs to the reviewing committee (MREC or CCMO).  The sponsor shall ensure that all relevant information about SAEs that are fatal or life-threatening is reported as soon as possible to the reviewing committee, and in any case no later than seven days after knowledge by the sponsor of such a case, and that relevant follow-up information is subsequently communicated within an additional eight days. All other SAEs shall be reported to the reviewing ethics committee  within a maximum of fifteen days of first knowledge by the sponsor.
  • The SAE reports have to be submitted digitally to the reviewing committee by the webportal  ToetsingOnline
  • The CCMO has to provide an annual overview of the number of SAEs which have been reported during the past year.

Notification procedure and guidance
A guidance document will be developed by the CCMO and the Dutch Association of Ethics Committees (NVMETC) for the assessment of the notification procedure of SAE's by the reviewing committee (MREC or CCMO). After all, it is possible that not all SAE's have to be reported immediately, but instead to submit SAE line-listings. The procedure for SAE reporting and notification should be described in the research protocol and assessed by the reviewing committee. This procedure is leading for investigator and sponsor during their conduct of the study.
The guidance for MRECs will correspond as much as possible to already existing European legislation. Also it is aimed to reduce the administrative burden for investigators, sponsors and reviewing committees arising from this amendment to a minimum. The guidance document will soon be available.

Transitional provision
This WMO amendment has no transitional provision. From October 1, 2015, all ongoing studies and new submissions have to meet the new legislation for SAE reporting.