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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:

Results in death,

Is life-threatening,

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.

Requires inpatient hospitalization or prolongation of existing hospitalization,

Results in persistent or significant disability/incapacity, or

Is a congenital anomaly/birth defect.

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.