Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition). William Gregory
Suspected adverse (drug) reaction or serious adverse reaction (SAR), Adverse effect, Undesirable effect (see EMA GVP Module Annex 1 Definitions).
“All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.” This means “that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.” (ICH E2A)
“A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function.” (ICH E2A)
EMA (GVP Module Annex I Definitions): A response to a medicinal product which is noxious and unintended. Response in this context means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility (see GVP Annex I). An adverse reaction, in contrast to an AE, is characterized by the fact that a causal relationship between a medicinal product and an occurrence is suspected. For regulatory reporting purposes, if an event is spontaneously reported, even if the relationship is unknown or unstated by the healthcare professional or consumer as the primary source, it meets the definition of an adverse reaction.
Therefore, all spontaneous reports notified by healthcare professionals or consumers are considered suspected adverse reactions, since they convey the suspicions of the primary source, unless the primary source specifically states that they believe the event to be unrelated or that a causal relationship can be excluded.
Serious Adverse Event and Serious Adverse Reaction (SAE/SAR)
A key difference between an “AE” and an “AR” is the concept of causality. An “event” is merely something “bad” that occurs, but a “reaction” captures the concept of a relationship between the event and drug exposure.
A serious AE (experience) or serious AR is any untoward medical occurrence that at any dose:
Note: The term life-threatening in the definition of serious refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe.
Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate in other situations, such as important medical events (IMEs) that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above. These should also usually be considered serious.
Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or development of drug dependency or drug abuse (ICH E2A).
The EMA considers any suspected transmission via a medicinal product of an infection agent to be a serious adverse reaction.
Note that an event or reaction may meet one or more of the criteria for seriousness simultaneously. Only one is needed, however, to consider the event or reaction to be serious. For an individual case safety report (ICSR) to be serious, it takes only one serious AE out of all the AEs present. To be a non-serious ICSR, all the AEs must be non-serious.
FDA’s definition of a serious event or reaction for clinical trials (21CFR312.32(a)) is as follows:
An AE or suspected adverse reaction is considered ‘‘serious’’ if, in the view of either the investigator or sponsor, it results in any of the following outcomes: Death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.
FDA’s definition of a suspected adverse reaction for clinical trials is as follows:
Any adverse event for which there is a reasonable possibility that the drug caused the adverse event. For the purposes of IND safety reporting, ‘‘reasonable possibility’’ means there is evidence to suggest a causal relationship between the drug and the adverse event. Suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any adverse event caused by a drug.
Non-serious Adverse Event and Non-serious Adverse Reaction (NSAE/NSAR)
An event or reaction is non-serious when it does not meet any of the criteria for seriousness.
Suspected Adverse (Drug) Reaction (SAR/SADR) — FDA
This includes any AE for which there is a reasonable possibility that the drug caused the AE. For the purposes of IND safety reporting, “reasonable possibility” means there is evidence to suggest a causal relationship between the drug and the AE. Suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any AE caused by a drug.
The point here is the word suspected, which means some level of causality with the drug in question, is present. It may be serious or non-serious.
Serious, Unexpected, Suspected Adverse Reaction (SUSAR)
EMA uses this phrase for an SAR in a clinical trial that is serious, not listed (i.e., unexpected) in the reference safety information, e.g., investigator brochure, and suspected to be due to the drug in question. See the definitions for serious and unexpected. The FDA does not use this definition or initialism formally for cases, though the concept is similar to SUSAR; FDA wording for this concept is “Suspected, Unexpected, Serious Adverse Reaction”. Such an SAR will ordinarily trigger an expedited report in the EU and consideration of expedited reporting to FDA (see below). The acronym “SUSAR” is only applied to clinical trial data, i.e., it does not apply to spontaneous reports in the post-marketing phase.
Serious, Expected, Suspected Adverse Reaction
EMA uses this phrase for an SAR in a clinical trial that is serious, listed (i.e., expected) in the reference safety information, e.g., investigator