Tooltip Categories: Adverse Events

Unexpected adverse event (DHHS OHRP): Any adverse event occurring in one or more subjects in a research protocol, the nature, severity, or frequency of which is not consistent with either: 1) the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol–related documents, such as the IRB-approved research protocol, any applicable investigator’s brochure (IB), and the current IRB-approved Informed Consent Form (ICF), and (b) other relevant sources of information, such as product labeling and package insert; or 2) the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event. OHRP: Unanticipated Problems Involving Risks & Adverse Events Guidance

Unexpected adverse event (FDA IND): An adverse event or suspected adverse reaction that is not listed in the investigator’s brochure or is not listed at the specificity or severity that has been observed; or, if an investigator’s brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the current Investigational New Drug (IND) application. FDA: 21 CFR 312.32: IND Safety Reporting; FDA: Safety Reporting Requirements for INDs and BA/BE Studies

Unexpected Adverse Drug Reaction (ICH GCP): An adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., investigator’s brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product). ICH GCP, 1.60

UPIRSO (DHHS OHRP): Any incident, experience, or outcome that meet all of the following criteria:

1. is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
2. is related or possibly related to a subject’s participation in the research; and
3. suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized. OHRP: Unanticipated Problems Involving Risks & Adverse Events Guidance

UPIRSO (UNC-Chapel Hill OHRE): Any incident, experience, outcome, or new information that:

1. Is unexpected (in terms of nature, severity, or frequency); and
2. Is at least possibly related to participation in the research; and
3. Indicates that subjects or others are at a greater risk of harm (including physical, psychological, economic, legal or social harm) than was previously known or recognized. UNC-Chapel Hill OHRE SOP 1401

Serious Adverse Event (DHHS OHRP): Any adverse event that 1) results in death; 2) is life-threatening (places the subject at immediate risk of death from the event as it occurred); 3) results in inpatient hospitalization or prolongation of existing hospitalization; 4) results in a persistent or significant disability/incapacity; 5) results in a congenital anomaly/birth defect; or 6) based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the 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). Modified from the definition of serious adverse drug experience in FDA regulations at 21 CFR 312.32(a). OHRP: Unanticipated Problems Involving Risks & Adverse Events Guidance; FDA: 21 CFR 312.32, IND Safety Reporting

Serious Adverse Event (FDA IND): An adverse event 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 adverse event, 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: 21 CFR 312.32, IND Safety Reporting; FDA: Safety Reporting Requirements for INDs and BA/BE Studies

Serious Adverse Event (ICH GCP): Any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. ICH GCP, 1.50

Life-threatening adverse event (FDA IND): An adverse event or a suspected adverse reaction is considered life-threatening if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a more severe form, might have caused death. FDA: 21 CFR 312.32, IND Safety Reporting; FDA: Safety Reporting Requirements for INDs and BA/BE Studies