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Unexpected adverse event

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An Adverse Event (AE) or Adverse Reaction (AR) that is not consistent with the known information/characteristics of the test article. Unexpected adverse events or reactions are defined by the Department of Health and Human Services (DHHS) Office for Human Research Protections (OHRP), the Food and Drug Administration (FDA), and the International Council for Harmonisation (ICH) as follows:  

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

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