Table 5. Definitions of adverse events.
| Term | Definition |
|---|---|
| Adverse Event (AE) | Any untoward medical occurrence in a patient or clinical investigation subject occurring in any phase of the clinical study whether or not considered related to the study drug. This includes an exacerbation of pre-existing conditions or events, intercurrent illnesses, or drug interactions. Anticipated day-to-day fluctuations of pre-existing conditions, that do not represent a clinically significant exacerbation, will not be considered AEs. Discrete episodes of chronic conditions occurring during a study period will be reported as adverse events to assess changes in frequency or severity.
Unsolicited adverse events will be documented in terms of a medical diagnosis(es). When this is not possible, the AE will be documented in terms of signs and symptoms observed by the investigator or reported by the subject. Pre-existing conditions or signs and/or symptoms (including any which are not recognized at study entry but are recognized during the study period) present in a subject prior to the start of the study will be recorded on the Medical History form within the subject's case report form (CRF). |
| Adverse Reaction (AR) | An untoward and unintended response in a participant to an investigational medicinal product which is related to any dose administered to that participant.
The phrase "response to an investigational medicinal product" means that a causal relationship between a trial medication and an AE is at least a reasonable possibility, i.e., the relationship cannot be ruled out. All cases judged by either the reporting medically qualified professional or the Sponsor as having a reasonable suspected causal relationship to the trial medication qualify as adverse reactions. It is important to note that this is entirely separate to the known side effects listed in the SmPC. It is specifically a temporal relationship between taking the drug, the half-life, and the time of the event or any valid alternative aetiology that would explain the event. |
| Serious Adverse Event (SAE) | A serious adverse event is any untoward medical occurrence that:
• results in death • is life-threatening • requires inpatient hospitalisation or prolongation of existing hospitalisation • results in persistent or significant disability/incapacity • consists of a congenital anomaly or birth defect Other ‘important medical events’ may also be considered serious if they jeopardise the participant or require an intervention to prevent one of the above consequences. NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. “Hospitalisation” signifies that the subject has been detained (usually involving an overnight stay) at a hospital for observation and/or treatment above that routinely offered at the inpatient trial facility. When in doubt as to whether hospitalisation occurred or was necessary, the adverse event will be considered as serious. Hospitalisation for elective surgery or routine clinical procedures, which are not the result of an adverse event, will not be considered adverse events and should be recorded on a clinical assessment form and added to the CRF. |
| Serious Adverse Reaction (SAR) | An adverse event that is both serious and, in the opinion of the reporting Investigator, believed with reasonable probability to be due to one of the trial treatments, based on the information provided. |
| Suspected Unexpected Serious Adverse Reaction (SUSAR) | An adverse reaction, the nature or severity of which is not anticipated based on the applicable product information is considered as an unexpected adverse drug reaction. Where the adverse reaction is also considered to have a possible, probable, or definite relationship with the drugs given, and also meets the criteria for a serious adverse reaction, it is termed a Suspected Unexpected Serious Adverse Reaction (SUSAR). These events are subject to expedited reporting as for SAEs. |
To avoid confusion or misunderstanding of the difference between the terms ‘serious’ and ‘severe,’ the following note of clarification is provided: ‘severe’ is often used to describe intensity of a specific event, which may be of relatively minor medical significance. ‘Seriousness’ is the regulatory definition supplied above.
Detailed guidance can be found here:
http://ec.europa.eu/health/files/eudralex/vol-10/2011_c172_01/2011_c172_01_en.pdf