Reporting Problems and Adverse Events
Requirements for Reporting
All problems or adverse events that occur during the course of an approved research project must be reported to the IRB. According to federal regulations, problems or potential adverse reactions that were anticipated by the researcher at the time of approval must be reported at periodic review or closure. Problems or adverse events related to the research that were not anticipated must be reported promptly after being discovered by the investigator, either within 7 or 14 days, depending on the seriousness of the event, as outlined below. Unfortunately, these regulations are somewhat complex, so a good rule of thumb is if anything unexpected occurs during your project, such as data being lost or stolen, a participant becoming upset, or a research procedure not being carried out as approved, simply send an email to the IRB Administrator and report it.
Anticipated (expected) problems are those that involve potential risks previously described to the IRB, and to participants in the consent form and other participant materials. Anticipated problems should be reported in summary form at the time of IRB continuing review or project closure, whichever comes first. For example, emotional distress is a possible outcome of the research anticipated at the outset, this event should be reported at the time of the next review.
Unanticipated problems are those that have not previously been noted as potential risks of the research to the IRB and the participants, and which suggest that the research places participants or others at a greater risk of harm (physical, psychological, social, or economic) than was previously known or recognized. When unanticipated problems occur, the investigator should assess whether or not the incident, experience, or outcome is related to the research. If not, the problem should be reported in summary form at the time of continuing review. If, in the opinion of the investigator, the problem or event is possibly, probably or definitely related to the research procedures, it must be reported to the IRB within 14 days of when the investigator learns of it.
Adverse Events are defined as any untoward or unfavorable medical occurrences in one or more human participants, including any abnormal sign, symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research. Adverse events include both physical and psychological harm, but not social, economic, or other kinds of harm. Instances of serious harm (death, disability, or hospitalization) that are unexpected are referred to as Serious Adverse Events.
In summary, Unanticipated Problems are unexpected, related to the research, and involve risk. Those that involve physical and psychological harm are called Adverse Events. (Only Adverse Events that were unexpected are considered Unanticipated Problems.) Thus, the following guidelines must be followed for reporting Unanticipated Problems and/or Adverse Events:
- Adverse Events (involving psychological or physical harm) that were not expected must be reported to the IRB within 7 days of the investigator learning of it, whether or not they are related to the research.
- Other Unanticipated Problems (involving social, economic or other harm) that were not expected must be reported to the IRB within 14 days of the investigator learning of it, if they are related to the research. If they are not related, these can wait until the continuing review or closure point.
- Serious Adverse Events, which involve death, hospitalization, and disability, that were not expected must be reported within 7 days to the IRB, whether related to the research or not.
- Any problems or events that were anticipated should be reported at continuing review or closure.
For example, the following events are considered Unanticipated Problems which must be reported within the 7 day time frame, using the Problem-Event Reporting form:
- Any event, which in the opinion of the local investigator, was unanticipated, involved risk to participants or others, and may have been related to the research procedures;
- Any accidental or unintentional change to the IRB-approved protocol that involves risk or has the potential to recur;
- Any deviation from the protocol taken without prior IRB review to eliminate apparent immediate hazard to a research subject;
- Any publication in the literature, interim result, or other finding that indicates an unexpected change to the risk/benefit ratio of the research;
- Any breach in confidentiality that may involve risk to the subject or others;
- Any complaint of a subject that indicates an unanticipated risk or that cannot be resolved by the research staff; or
- Any other possibly related event which in the opinion of the investigator constitutes an unanticipated risk of physical or psychological harm.
When an investigator has an Unanticipated Problem or Adverse Event to report, he or she must complete the Problem-Event Reporting Form, sign it, and mail or drop it off at the IRB office. The IRB Administrator will review it and forward it to the IRB Chairperson. If the Chair determines it warrants full board consideration, it will be presented to the committee at its next regularly scheduled meeting, unless an immediate meeting is called for. The Chair and/or the Board will determine what, if any, action should be taken in response to the problem or event.
Examples of corrective actions or substantive changes that might need to be considered in response to an unanticipated problem or adverse event include:
- review/approval of changes to the research protocol that were initiated by the investigator prior to obtaining IRB approval to eliminate apparent immediate hazards to participants;
- modification of inclusion or exclusion criteria to mitigate the newly identified risks;
- implementation of additional procedures for monitoring participants;
- suspension of enrollment of new participants;
- suspension of research procedures in currently enrolled participants;
- modification of informed consent documents to include a description of newly recognized risks; and
- provision of additional information about newly recognized risks to previously enrolled participants.
IRB Reporting to Others
In some cases, the IRB is required by Federal Regulations to report incidents to the Office of Human Research Protections (OHRP), typically when one of the following occurs: a) Unanticipated Problem (unexpected, related to research, and involving risk); b) Serious or continuing noncompliance by an investigator; or c) Suspension or termination of a protocol. Unanticipated Problems must be reported “promptly”, which is to be defined by the institution according to the nature and severity of the problem, but reports to OHRP are encouraged within 4 weeks of the IRB receiving the information. Upon receipt, the OHRP will assess the adequacy and timeliness of the institution’s response to the problem. When a report is sent to the OHRP, a copy will also be sent to the investigator, and possibly his/her department head, the dean of the college, and the Provost.
Example of an Unanticipated Problem that is not an Adverse Event. Investigator must report promptly and IRB must report it to the OHRP.
An investigator conducting behavioral research collects individually identifiable sensitive information about illicit drug use and other illegal behaviors by surveying college students. The data are stored on a laptop computer without encryption, and the laptop computer is stolen from the investigator’s car on the way home from work. This is an unanticipated problem that must be reported because the incident was (a) unexpected (i.e., the investigators did not anticipate the theft); (b) related to participation in the research; and (c) placed the participants at a greater risk of psychological and social harm from the breach in confidentiality of the study data than was previously known or recognized.
Examples of Adverse Events that are not Unanticipated Problems. Investigator reports these to the IRB at continuing review and IRB does not report to OHRP.
An investigator is conducting a psychology study evaluating the factors that affect reaction times in response to auditory stimuli. In order to perform the reaction time measurements, participants are placed in a small, windowless soundproof booth and asked to wear headphones. The IRB-approved protocol and informed consent document describe claustrophobic reactions as one of the risks of the research. The 20th subject enrolled in the research experiences significant claustrophobia, resulting in the participant withdrawing from the research. This example is not an unanticipated problem because the occurrence of the claustrophobic reactions in terms of nature, severity, and frequency was expected.
An investigator performs prospective medical chart reviews to collect medical data on premature infants in a neonatal intensive care unit (NICU) for a research registry. An infant, about whom the investigator is collecting medical data for the registry, dies as the result of an infection that commonly occurs in the NICU setting. This example is not an unanticipated problem because the death of the subject is not related to participation in the research, but is most likely related to the infant’s underlying medical condition.
Example of Adverse Event that is an Unanticipated Problem. Investigator must report it promptly to the IRB and the IRB must report it to OHRP.
A behavioral researcher conducts a study in college students that involves completion of a detailed survey asking questions about early childhood experiences. The research was judged to involve no more than minimal risk and was approved by the IRB chairperson under an expedited review procedure. During the completion of the survey, one participant has a transient psychological reaction manifested by intense sadness and depressed mood that resolved without intervention after a few hours. The protocol and informed consent document for the research did not describe any risk of such negative psychological reactions. Upon further evaluation, the investigator determines that the participant’s negative psychological reaction resulted from certain survey questions that triggered memories of physical abuse as a child. The investigator had not expected that such reactions would be triggered by the survey questions. This is an example of an unanticipated problem that must be reported in the context of social and behavioral research because, although not serious, the adverse event was (a) unexpected; (b) related to participation in the research; and (c) suggested that the research places participants at a greater risk of psychological harm than was previously known or recognized.
The Office of Human Research Protections (OHRP), Department of Health and Human Services. “Guidance on Reviewing and Reporting Unanticipated Problems involving Risks to Subjects or Others and Adverse Events.” January 15, 2007.
45 CFR 46.103
45 CFR 46.111
45 CFR 46.109(e)
45 CFR 46.113