What is a Serious Adverse Event?
An adverse event is any undesirable experience associated with the use of a medical product in a patient. The event is serious and should be reported to FDA when the patient outcome is:
Report if you suspect that the death was an outcome of the adverse event, and include the date if known.
Report if suspected that the patient was at substantial risk of dying at the time of the adverse event, or use or continued use of the device or other medical product might have resulted in the death of the patient.
Hospitalization (initial or prolonged)
Report if admission to the hospital or prolongation of hospitalization was a result of the adverse event.
Emergency room visits that do not result in admission to the hospital should be evaluated for one of the other serious outcomes (e.g., life-threatening; required intervention to prevent permanent impairment or damage; other serious medically important event).
Disability or Permanent Damage
Report if the adverse event resulted in a substantial disruption of a person's ability to conduct normal life functions, i.e., the adverse event resulted in a significant, persistent or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities and/or quality of life.
Congenital Anomaly/Birth Defect
Report if you suspect that exposure to a medical product prior to conception or during pregnancy may have resulted in an adverse outcome in the child.
Required Intervention to Prevent Permanent Impairment or Damage (Devices)
Report if you believe that medical or surgical intervention was necessary to preclude permanent impairment of a body function, or prevent permanent damage to a body structure, either situation suspected to be due to the use of a medical product.
Other Serious (Important Medical Events)
Report when the event does not fit the other outcomes, but the event may jeopardize the patient and may require medical or surgical intervention (treatment) to prevent one of the other outcomes. Examples include allergic brochospasm (a serious problem with breathing) requiring treatment in an emergency room, serious blood dyscrasias (blood disorders) or seizures/convulsions that do not result in hospitalization. The development of drug dependence or drug abuse would also be examples of important medical events.
The definitions are as follows (cf. the Executive Order on clinical trials):
adverse event (AE): any untoward medical occurrence in the patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment
adverse reaction (AR): any untoward and unintended response to an investigational medicinal product related to any dose administered
unexpected adverse reaction (UAR): an adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g. Investigator's Brochure for an unauthorized investigational product or summery of product characteristics for an authorized product)
serious adverse event (SAE) or serious adverse reaction (SAR): an untoward medical occurrence or affect that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalization, results in persistent or significant disability, or is a congenital anomaly or birth defect
Reference Safety Information:
The reference safety information (RSI) is used to assess whether a serious adverse reaction (SAR) is considered to be expected or unexpected. For approved medicinal products, it will typically be the Summary of Product Characteristics (SmPC) (section 4.8), if the medicinal product is used within the approved indication. For medicines under development, it will be a section / table in Investigator's Brochure (IB). Sponsor must choose an SmPC, which is used to assess the safety of subjects in the trial. This SmPC will be the RSI during the trial at all sites. Prior to initiation of the trial, sponsor must submit the correct RSI to all sites, and it must be clearly stated when the document was approved. This date is the version number of the RSI. If the RSI is changed, it must be submitted to the Danish Medicines Agency as a significant change, unless submitted at the same time as the annual safety report. The RSI shall not be submitted to the Scientific Ethics Committee. If a new RSI is approved, the sponsor must forward the new RSI to all sites.