Adverse Events

The definitions of adverse events are as follows:

Adverse Event (AE): An AE is defined as any untoward medical occurrence in a study participant that may or may not have a causal relationship with the study intervention. An AE can therefore be an unfavorable and unintended sign (including abnormal laboratory findings), symptom (nausea and loose stools), or disease that occurs during the study, whether or not related to the study intervention.

Anticipated problems/AE’s are defined as those that are already described as potential risks in the consent form, the protocol, or are part of an underlying disease.

Unanticipated problems/AE’s are defined as any serious event (including on-site and off-site adverse events, injuries, side effects, deaths or other problems) which in the opinion of the local investigator was unanticipated, serious, and was at least possibly related to the research procedures, including:

  • Any serious accidental or unintentional change to the IRB-approved protocol that involves risk or has the potential to recur;
  • Any deviation from the protocol taken without prior IRB review to eliminate apparent immediate hazard to a research subject;
  • Any publication in the literature, safety monitoring report (including Data and Safety Monitoring Reports), interim result or other finding that indicates an unexpected change to the risk/benefit ratio of the research;
  • Any breach in confidentiality that may involve risk to the subject or others;
  • Any complaint of a subject that indicates an unanticipated risk or that cannot be resolved by the research staff;or
  • Any other serious and possibly related event which in the opinion of the investigator constitutes an unanticipated risk.

Serious Adverse Event (SAE): An SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or result in a congenital anomaly or birth defect. Other important medical events requiring medical or surgical intervention to prevent a serious outcome would also be considered SAEs. Definitions of SAEs are listed as follows:

  • Death:  An event that results in the death of a subject
  • Life Threatening:  An event, which, in the opinion of the physician, would have resulted in immediate fatality if medical intervention had not been taken.
  • Hospitalization:  An event that results in an admission to the hospital for any length of time. This does not include an emergency room visit or an admission to an outpatient facility.
  • Prolongation of Hospitalization:  An event that occurs while the study subject is hospitalized and prolongs the subject’s hospital stay.
  • Persistent or Significant Disability:  An event that results in a condition that substantially interferes with the activities of daily living of a subject.  “Disability” is not intended to include experiences of relatively minor medical significance such as headache, vomiting or accidental trauma (e.g. sprained ankle).
  • Congenital Anomaly:  An anomaly detected at or after birth or any anomaly that results in fetal loss.
  • Important Medical Event: An important medical event may not be immediately life-threatening or result in death or hospitalization but requires intervention(s) to prevent serious outcome based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above.

Severity: Adverse events, but not SAEs, will be categorized into four different levels of severity: mild, moderate, severe, or very severe.  These categories are defined as follows:

  • Mild: Transient and easily tolerated.
  • Moderate: Results in a modification or interruption of the subject’s usual activities or care and may require discontinuation of the study intervention
  • Severe: Results in considerable interference with the subject’s usual activities or care and may require discontinuation of study intervention.
  • Very Severe: Results in the need for urgent medical care and likely requires discontinuation of the study intervention.

Attribution: The relationship between adverse events and the study intervention should be evaluated and graded as none, remote, possible, probable, or highly probable. Clinical investigators are responsible for determining the relationship between study intervention and adverse events.

Timeline for Reporting AEs and SAEs

Anticipated Adverse Events: These will be reported in summary form annually to the IRB during continuing review, regardless of whether classified as severe or related to the study intervention.

Unanticipated Adverse Events: Unanticipated problems will be reported to the IRB within 10 working days of the investigators being notified of the event.

Serious Adverse Events: Serious adverse events will be reported the IRB within 24 hours of the investigators being notified.