7.3 Definitions Page 20 of 50 IRB Protocol No. 12367 Version Date: 10/24/2017 Version: 09 A dverse event (AE) - An adverse event is any untoward medical experience or change of an existing condi tion that occurs during or after treatment, whether or not it is considered to be related to the protocol intervention. Unexpected Adverse Event [21 CFR 312.32 (a) – An adverse event is unexpected if it is not listed in the i nvestigator’s brochure and/or package insert; is not listed at the specificity or severity that has been observed; is not consistent with the risk information described in the protocol and/or consent; is not an expected natural progression of any underlying disease, disorder, condition, or predisposed risk factor of the research participant experiencing the adverse event. Expected Adverse Event - Any event that does not meet the criteria for an unexpected event OR is an expe cted natural progression of any underlying disease, disorder, condition, or predisposed risk factor of the research participant experiencing the adverse event. Serious Adverse Event (SAE) [21 CFR 312.32] is defined as any expected or unexpected adverse event that results in any of the following outcomes:  De ath  I s life-threatening experience (places the subject at immediate risk of death from the event as it occurred)  Unplanned hospitalization ( equal to or greater than 24 hours) or prolongation of existing hospitalization  A pe rsistent or significant disability/incapacity  A c ongenital anomaly/birth defect  S econdary Malignancy  Any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the outcomes listed above (examples of such events include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood dyscrasisas of convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse). Unanticipated problem (UP) – Any incident, experience, or outcome that meets all three of the following criteria: 1.