Adverse Event Definitions. The investigator is responsible for reporting all AEs that are observed or reported during the study, regardless of their relationship to study drug or clinical significance. If there is any doubt as to whether a clinical observation is an AE, the event should be reported. An AE is any event or other untoward medical occurrence, including those AEs that result from dosing errors, which may present during administration of a study drug or during a reasonable follow-up period and which does not necessarily have a causal relationship with this treatment. An AE is any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. All AEs will be followed until the AE is resolved or stabilized as determined by the investigator and/or the medical monitor. A treatment-emergent AE (TEAE) is defined as any event not present before exposure to study drug or any event already present that worsens in intensity or frequency after exposure to study drug. An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all suspected adverse reactions for which there are reasons to conclude that the drug caused the event. A suspected adverse reaction is any AE for which there is a reasonable possibility that the study drug caused the AE. For the purposes of IND safety reporting, “reasonable possibility” means that there is evidence to suggest a causal relationship between the drug and the AE. A suspected adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which means any AE caused by a study drug. An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the TPOXX full prescribing information or at the specificity or severity that has been observed with the study drug being tested. For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the TPOXX full prescribing information referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) if the TPOXX full prescribing information listed only cerebral vascular accidents. “Unexpected,” as used in this definition, also refers to AEs or suspected adverse reactions that are mentioned in the TPOXX full prescribing inf...
Adverse Event Definitions. An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Subjects will be instructed to contact the investigator at any time after signing the ICF if any symptoms develop. A treatment-emergent AE is defined as any event not present before exposure to study drug or any event already present that worsens in intensity or frequency after exposure. A suspected adverse reaction is any AE for which there is a reasonable possibility that the study drug caused the AE. For the purposes of investigational new drug safety reporting, “reasonable possibility” means that there is evidence to suggest a causal relationship between the study drug and the AE. A suspected adverse reaction implies a lesser degree of certainty about causality than an adverse reaction. An adverse reaction is any AE caused by a study drug. Adverse reactions belong to a subset of all suspected adverse reactions and indicate that there are reasons to conclude that the study drug caused the event. An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the investigator’s brochure or if it occurs with specificity or severity that has not been previously observed with the study drug being tested. An AE or suspected adverse reaction is considered an SAE/suspected unexpected serious adverse reaction if, in the view of either the investigator or sponsor, it results in any of the following outcomes: • Death • Life-threatening AE • Inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions • Congenital anomaly or 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 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. An AE or suspected adverse reaction is considered “life threatening” if, in the view of either the investigator or sponsor, its occurrence places the subject at immediate risk of death. It do...
