Event Reporting: Unanticipated Problems, Adverse Events and Other Problems

The Code of Federal Regulations (CFR) 45 CFR 46.108(a)(4)(i) requires Institutional Review Boards for the Protection of Human Subjects (IRBs) to have written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the federal department or agency head of any unanticipated problems involving risks to subjects or others.

Definitions

Unanticipated Problem (UP)

Any incident, experience, or outcome that meets all of the following criteria:

  1.  Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
  2. Related or possibly related to a subject’s participation in the research; and
  3. Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized.

Adverse Event (AE)

Adverse Event is any unintended negative experience associated with the study materials or research procedures. Adverse events include both physical and psychological harms; although they most commonly occur in the context of biomedical research, they also can occur in the context of social and behavioral research.

Serious Adverse Events are adverse events that result in any of the following outcomes: death; a life-threatening experience; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; or a congenital anomaly/birth defect.

Non-Serious Adverse Event is any event that causes interference with routine daily activities without major discomfort and these interferences do not persist. Non-serious events also include events that that are easily tolerated and do not affect participation in routine daily activities.

Protocol Deviation

Protocol Deviation is any alteration/modification to the IRB-approved protocol, whether intentional or inadvertent, that is not approved by the IRB prior to its initiation or implementation.

Minor Protocol Deviation is an incident involving noncompliance with the protocol but one that typically does not have a significant effect on the subject’s rights, safety, welfare, or on the integrity of the study data. Examples include over-enrollment of participants and not collecting samples at the exact timeframes indicated in the application.

Major Protocol Deviation is a more serious incident involving noncompliance with the protocol usually involving critical study parameters. Major protocol deviations generally affect the subject’s rights, safety, or welfare, or the integrity of the study data.

Protocol Exception is a temporary deviation from the protocol that has been approved by the IRB before its initiation. Protocol exceptions are usually for a specific subject (e.g., allowing enrollment of a subject who is close to, but outside of, the age eligibility).

Research Participant Complaint

As a study researcher, you should promptly respond to any study-related concern or complaint you receive or of which you are aware. It is also the responsibility of the researcher to try to resolve the issue in a timely manner. Only significant complaints that impact the participant’s safety, rights or welfare need to be reported to the IRB. Any complaints that require the researcher to modify the application must also be reported to the IRB. Minor complaints such as late payment or payment not received do not need to be reported to the IRB. If unsure if a complaint must be reported to the IRB, please reach out to the IRB office at umric@maine.edu.

Investigator Responsibilities

Investigators must report the following:

  • Any adverse event (AE) that is unexpected and is related or possibly related to the participation in the research.
  • Any unanticipated problem (UP).
  • Any breach of confidentiality (which includes lost or stolen confidential information).
  • Any significant complaint from the participants that impacts their safety, rights, or welfare, or a complaint that requires a modification to the application.
  • Any other event that is unanticipated and indicates that the research study places subjects or others (e.g., other investigators, research assistants, students, the public, family members or partners of subjects) at an increased risk of harm or otherwise adversely affects the rights, welfare, or safety of subjects or others.
  • Protocol deviations.
  • Any event that requires prompt reporting to the sponsor.

Reporting Schedule:

  • Reportable events that are life threatening or which have resulted in death must be reported within 24 hours.
  • Reportable events that are not life-threatening or resulted in death should be reported within 10 business days.
  • Minor protocol deviations should be reported within 30 days.
  • Major protocol deviations should be reported within 10 business days.

How to report:

Reports should be submitted via email to umric@maine.edu

For serious adverse events, the researcher should provide information on how the serious adverse event relates to the drug, device, intervention of study protocol, and whether a change in the application is needed to minimize risk.

Review Process Overview

  1. The IRB Office will review the report and ask for clarifications as needed.
  2. The IRB Office will forward the report to the IRB Chair. The Chair will determine what action, if any, is required. The Chair may also ask a subcommittee to review the report, submit it to the next IRB meeting, or schedule an emergency IRB meeting.
  3. The IRB Office will assist in communicating with the researcher the results of the review and any necessary next steps. The IRB may suspend or terminate a protocol that has been associated with unexpected serious harm to subjects or others.
  4. The IRB Office is responsible for reporting the event to the Institutional Official (if necessary) and assist the researcher to report to the outside agency according to reporting requirements.

References