SUSARs Suspected Unexpected Serious Adverse Reactions (Suspected Unexpected Serious Adverse Reactions ) and SAEs in the entire study (these include foreign reports in case of international studies) should be submitted directly to the CCMO Central Committee on Research involving Human Subjects (Central Committee on Research involving Human Subjects ). SUSARs must be submitted to VWS Ministry of Health, Welfare and Sport (Ministry of Health, Welfare and Sport ) of the entire study, unless they have reported directly to EudraVigilance.
The following definitions are used for adverse events.
- Adverse Event: any untoward medical occurrence in a patient or clinical trial subject which does not necessarily have a causal relationship with any treatment.
- Adverse (Drug) Reaction: all untoward and unintended responses to an investigational medicinal product related to any dose administered.
- Serious Adverse Event (SAE Serious Adverse Event (Serious Adverse Event )): un undesired medical event involving a patient or test subject, which is not necessarily associated with the treatment, and is fatal, and/or is life-threatening for the subject, and/or makes hospital admission or an extension of the admission necessary, and/or causes persistent or significant invalidity or work disability, and/or manifests itself in a congenital abnormality or malformation, could, according to the person that carries out the research, have developed to a serious undesired medical event, but was however prevented due to premature interference.
- Unexpected Adverse Reaction: an adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g. investigator's brochure for an unauthorised investigational product or summary of product characteristics for an authorised product).
- Suspected Unexpected Serious Adverse Reaction (SUSAR Suspected Unexpected Serious Adverse Reaction (Suspected Unexpected Serious Adverse Reaction )): an unexpected adverse reaction that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect
By which deadline must notification be given?
SUSARs within the study which are life-threatening or have had fatal consequences, must be reported within 7 days after the sponsor was notified. All relevant information on the aftermath should be reported within an additional time period of 8 days. Other SUSARs should be reported within 15 days after the sponsor was notified. SUSARs from other studies with the same product should be reported in the semi-annual line listings, unless there are direct consequences for the study subjects within the study. In that case expedited reporting is needed within the above mentioned time periods.
SAEs that are fatal or life-threatening for the patient must be reported within 7 days after the sponsor has taken notice of this event. Other SAEs must be reported within 15 days. SAEs that require no immediate reporting according to the protocol can be reported in periodic line listings and the development safety update report. In some cases SAE reporting can be waived. The procedure of SAE reporting needs to be recorded in the clinical protocol (or in an addendum of the protocol).
Who should be notified of adverse events?
SUSARs and SAEs in the entire study (these include foreign reports in case of international studies) must be submitted directly to the CCMO. SAEs that must be reported within 7 or 15 days must also be reported in ToetsingOnline. The SAE will be automatically forwarded to the CCMO. SUSARs of investigator-initiated studies must be reported through ToetsingOnline. By filling out the SUSAR-form the reported SUSARs in the Netherlands are also entered into the EudraVigilance database. It is not yet required for commercial clinical research. These notifications should be submitted by email to email@example.com or by mail with reference to the NL-number of the study. Further information about reporting SUSARs and SAEs can be found at www.ccmo.nl.
Only SUSARs that have not yet been reported in EudraVigilance must be reported directly to VWS as the competent authority for gene therapy studies (firstname.lastname@example.org). There is no need to report to the competent authority directly if the SUSAR is already reported through ToetsingOnline since these messages are automatically forwarded to the relevant authorities.
What happens after notification?
The bodies involved have different procedures for the assessment and further processing of notification, often based on various legislation and regulations. This procedure uses those different procedures as a point of departure, although agreements have also been made between the bodies involved as to how cooperation and coordination can be achieved and improved. The intention is to make things simpler and clearer for the investigator. The primary aspects are the following:
- In principle, the bodies themselves maintain contact with the party that submitted the notification. This may include making a decision as to whether or not the research needs to be put ‘on hold’.
- When processing the notification, coordination between the bodies reduces the pressure on the notifying party as much as possible.