Conducting the Study - Identifying and Reporting Adverse and Unexpected Events - Biomedical Research

The principal investigator is responsible for detecting and documenting all adverse events in subjects and reporting this information to the study sponsor and, in some cases (as defined below), the IRB. An adverse event is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical treatment or procedure, regardless of whether it is considered related to participation in the study. Some adverse events may be classified as serious and/or unexpected. A serious adverse event is defined as any event that is fatal, life-threatening, requires or prolongs hospitalization, involves a persistent or significant disability or incapacity, involves a congenital anomaly and/or birth defect, or jeopardizes the subject and may require medical or surgical treatment to prevent one of the preceding outcomes. An unexpected event is any adverse event whose nature, severity, or frequency is inconsistent with the information in the consent form or current investigational brochure. An unexpected event is one that has not been previously observed. This includes events that are more serious (e.g., subject experiences an anaphylactic shock when a simple allergic response was expected) or occur more frequently than expected (although this is often difficult to determine).

All serious, unexpected adverse events must be reported to the IRB in a written notice within 48 hours of becoming known to the principal investigator (or as described in the protocol) and also potentially the Food and Drug Administration (FDA) or other governmental agencies. A form is available to help investigators fulfill this reporting requirement. Serious and non-serious expected adverse events as well as unexpected nonserious adverse events are to be reported as described in the investigator’s approved protocol. Each principal investigator is required to assess these adverse events, and to advise the IRB as to whether there is any need for changes to the protocol or consent form. The IRB will review these reports and may concur with the principal investigator or require further information and/or changes.

As defined in the protocol, investigators may also have to report adverse events to a government agency, such as the U. S. Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP), the National Institutes of Health (NIH), or the FDA, and/or to the study sponsor (whose reporting requirements may differ from Yale’s requirements). Study sponsors typically have extensive reporting requirements for adverse events, especially in multicenter trials, and typically distribute safety reports (describing these adverse events) to all investigators in the trial as well as to appropriate regulatory agencies. After receiving reports of serious and unexpected adverse events (directly from other investigators or the study sponsors), the Yale investigator is required to assess whether these adverse events will result in a change to the risk of participation, and if so, to report this to the Yale IRB. Summary reports distributed by study sponsors, which include recommendations and/or data summaries, should be forwarded to the IRB. The IRB must re-evaluate the acceptability of risks to subjects and decide whether to stop, revise, or continue to monitor the study. The latest information on investigator’s responsibilities for reporting to IRBs can be found on the IRB website.