Human Subjects 

51³Ô¹ÏºÚÁÏ is required to conduct continuing review of research to comply with the U.S. Office of Human Research Protections (OHRP), the Food and Drug Administration (FDA), and the 51³Ô¹ÏºÚÁÏ Human Subject Policy. Monitoring adverse reactions and unexpected events is part of this continuing review requirement (21 CFR 56.108 and 45 CFR 46.103).

An adverse event is any untoward occurrence in a research subject, which may or may not have a causal relationship with the study intervention/treatment.

Principal investigators (PIs) have an obligation to report an adverse event within five days of the occurrence. The 51³Ô¹ÏºÚÁÏ IRB adverse event reporting plan requires investigators to assess the adverse event and the relationship of the event to the study and report their findings to the Office of Research Integrity - Human Subjects Research within five days of the event via an Adverse Event Report. If the research involves sponsored drug, device, or biologics studies, the investigator is also required to report adverse events to the study sponsor and the Food and Drug Administration.

Investigator Reporting Procedures

The PI must ensure that written notification of adverse events is submitted to the Office of Research Integrity – Human Subjects Research. In addition to the Adverse Event Report, the PI should attach any additional information necessary in evaluating the adverse event (i.e., medical report). After review of the report, the IRB may seek input from the PI to determine whether the risk/benefit ratio has been affected by the adverse event and any harms to subjects from the adverse event.

IRB Review of Adverse Events

The IRB will consider whether the adverse event affected the risk/benefit ratio to subjects. As a result of this review, the IRB may:

  • Reconsider approval of the study
  • Require the investigator to modify the protocol to minimize risks to subjects
  • Require revision of the protocol to reflect the risks to subjects
  • Require subjects be re-consented
  • Require no additional action on the part of the PI

Adverse Event Definitions

Unexpected Adverse Event: An adverse event for which the specificity is not consistent with any of the following:

  • Approved protocol
  • Risk information in the consent form
  • Reasonably expected natural history and progression of the underlying disease or condition being studied

Serious Adverse Event: An adverse event that results in any of the following outcomes:

  1. Death
  2. A threat to life
  3. Inpatient hospitalization or prolongation of existing hospitalization
  4. Persistent or significant disability or incapacity
  5. Congenital anomaly or birth defect
  6. Causes cancer
  7. Is an overdose
  8. Any medical event that requires treatment to prevent one of the medical outcomes listed above

Related Adverse Event: An adverse event that is related to the use of the study drug, device, or intervention and one for which there is a reasonable possibility (e.g., strong temporal relationship) that the adverse event may have been caused by the drug, device, or intervention

Possibly Related Adverse Event: An adverse event that may have been caused by the drug, device, or intervention; however there is insufficient information to determine the likelihood of this possibility.

Unrelated Adverse Event: An adverse event that has seemingly no relationship to the study.

Additional Reporting Requirements for Sponsored Studies

A written notification of adverse experiences must be submitted to the study sponsor and the Food and Drug Administration (for drugs, devices, and biologics). The reporting requirements are as follows:

  • Adverse events must be reported immediately to the sponsor (except for those events that the protocol identifies as not needing immediate reporting). The sponsor protocol should indicate when and how adverse events are to be reported. It is likely that the sponsor will require this immediate report be followed promptly by detailed written reports of the event. Investigators should contact the study sponsor for specific reporting requirements.
  • Pursuant to 21 CFR 312.32, adverse events that are both serious and unexpected must be reported to the FDA. In the case of industry-sponsored protocols, reporting to the FDA is usually accomplished through the normal reporting channel (i.e., investigator to the sponsoring company to the FDA).
  • In the case of investigator-initiated research or research that does not involve funding from a sponsoring company, the principal investigator of the protocol assumes the responsibility to report adverse events to the FDA. In such instances, investigators should follow the reporting procedure of the FDA Medical Products Reporting Program .

OHRP provides additional guidance on unanticipated problems and adverse events on its .