During the course of a research study and sometimes even after the study has ended, it is the Principal Investigator’s (PI) responsibility to keep the IRB informed of any events or problems that may result in a change to the risk/benefit ratio (i.e. increase in risk or a decrease in anticipated benefit). This includes serious adverse events and adverse events that are unexpected and related to the research procedures. In addition, the UT Southwestern IRB requires researchers to track and report unanticipated problems that arise during the conduct of the study. Each of these types of reportable events or situations is detailed below.
Reporting Methods and Timeframes
The following events/incidents must be submitted to the IRB within the specified reporting timeframe, followed by timely follow-up reports, as appropriate.
Event/Incident occurring on UT Southwestern IRB-approved study ("Local"):
Type of Occurrence
Reporting Timeframe
Reporting Method
Serious Adverse Event
2 working days
Adverse Event Form
Unexpected AE
10 working days
Adverse Event Form
Unanticipated problem
2 working days
Adverse Event Form
Event/Incident occurring on multi-site study to a subject not enrolled on a UT Southwestern IRB-approved protocol ("off-site"):
Adverse Event: An untoward or undesirable experience associated with the use of a medical product/test article/procedure in clinical research.
Adverse Events (AEs) that occur on a UT Southwestern IRB-approved study are EXPECTED, if they are described as anticipated risks in the informed consent document or are planned/ known in advance (such as an elective surgery).
Unexpected Adverse Event: An Adverse event where the frequency and/or severity are not consistent with the Sponsor’s Brochure and/or the protocol narrative and consent form for the UT Southwestern IRB approved study.
Local Adverse Events that are unexpected are to be reported to the IRB via the Adverse Event Report as soon as possible, but not later than 10 working days after the local PI first learns of the event.
SERIOUS ADVERSE EVENT:Any adverse event that results in any of the following outcomes:
Death
Life-threatening situation
Inpatient hospitalization or prolongation of existing hospitalization
A persistent or significant disability/incapacity
A congenital anomaly/birth defect
Other health-related problem: An event that may not be life-threatening, or require hospitalization should be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Examples of Other health-related problems include but are not limited to:
allergic bronchospasm requiring intensive treatment in an emergency room
convulsions that do not result in inpatient hospitalization and;
development of drug dependency or drug abuse.
Researchers must report any serious adverse event (SAE) or experience occurring on a UT Southwestern IRB-approved study to the IRB via the Adverse Event Form as soon as possible, but not later than two working days after the LOCAL PI first learns of the event, and followed by any follow-up reports, as applicable. Local Serious Adverse Events must also be reported by the local PI to the funding agency or Study Sponsor and Regulatory Authorities (e.g., OHRP, FDA, NIH).
For multi-site investigations (clinical trials, cooperative group trials, NIH multi-site studies), unexpected SAEs occurringon non-UT Southwestern IRB approval protocols must also be reported to the IRB within two working days of the researchers' receipt of report, followed by any follow-up reports, as applicable.
Unanticipated problem Involving Risk to Participants or Others
UNANTICIPATEDPROBLEM:An Unanticipated Problem (UP) refers to any unexpected negative event that is usually non-medical in nature , involving anyone including participants, research staff, or others not directly related to the research.
Why do we need to look for and report unanticipated problems?
Investigators are responsible for trying to identify the benefits of research interventions as well as the risks. Precisely identifying the frequency of known risks is certainly important, and sometimes critical to determining whether a new intervention is better than existing treatments. But investigators also have an important responsibility to be on the lookout for unanticipated problems, which could dramatically affect the safety of a research intervention and which otherwise might not be recognized until after many people had been exposed to the risk.
Unanticipated problems can occur in clinical or non-clinical research settings, and per federal regulations, always require prompt reporting to the IRB, appropriate institutional officials, funding agency or sponsor, and regulatory authorities (e.g., OHRP, FDA, NIH).
Below are examples of events/situations (i.e., unanticipated problems) that would require reporting:
Any publication in the literature, safety monitoring report including a Data and Safety Monitoring Report, interim result, or other finding that indicates an unexpected change to the risk/benefit ratio of the research
A breach in confidentiality that may involve risk to an individual or others
Any independent safety monitoring reports or Data and Safety Monitoring Board reports if changes to the protocol narrative or consent form are required
Any subject complaint that indicates an unanticipated risk or which cannot be resolved by the research staff
An undesirable or unintended risk to someone other than the participant as a result of the research study (e.g., research coordinator assaulted by angry participant).
Unanticipated problems should be reported to the IRB as soon as possible, but no later than two working days after the local research team first learns of the incident, and followed by any follow-up reports, as applicable.
Safety Report (SR) alerts are issued to inform researchers using the same pharmacological compound about serious adverse events or reactions in patients/participants who are not necessarily enrolled as subjects on a given UTSWMC study. These reports usually are issued by the FDA or by a drug/device manufacturer. For example, the SSRI alert from the FDA (adolescents and elderly) and the FDA/Manufacturer alert on Cox-II inhibitors.
Safety Reports should be submitted to the IRB via the Adverse Event Form reporting process as soon as possible, but no later than two working days after the research team's receipt of the alert.
Additional Serious Adverse Event Reporting Requirements for Human Gene Transfer Research
Lead Researchers of human gene transfer (a.k.a. "gene therapy") protocols have extra AE reporting responsibilities. In addition to submitting AE/Unanticipated Problems reports to the UT Southwestern IRB, they also must complete and submit the NIH Office of Biotechnology Activities' (OBA) Serious Adverse Event report form when a subject on a gene transfer protocol experiences a hospitalization or a death. If the gene transfer study is supported by an external sponsor, this reporting should be coordinated with the sponsor. Detailed requirements for SAE submissions are provided on the OBA rDNA and Gene Transfer website.
Failure to report gene transfer SAEs to the federal oversight bodies (FDA, NIH-OBA) may result in sanctions for the individual researcher and for the institution. For more information regarding the additional AE reporting responsibilities for human gene transfer research, please contact the UT Southwestern IRB Manager.
Reporting timelines for Local Serious Adverse Event reporting should be followed for Adverse Events which occur on any Human Gene Transfer Research Study.
Serious Adverse Events or Unanticipated Problems related to a Humanitarian Use Devices (HUD)
When the physician or health care provider receives or otherwise becomes aware of information, from any source, that reasonably suggests that a HUD has or may have caused or contributed to the death or serious injury of a patient, the physician or health care provider must report such findings on an AE Report form to the IRB and must be reported to the FDA as soon as possible, but no later than two working days after the physician first learns of the event or problem. This reporting is in addition to, not a substitute for, FDA and/or manufacturer reporting requirements in accordance with 21 CFR 803.30. The physician or health care provider must promptly report any FDA action regarding the death or serious injury to the patient to the IRB.
The IRB has the authority to suspend or terminate approval of research that has been associated with unexpected serious harm to participants or others. When the IRB takes such action, it is required to provide a statement of reason for the action and to promptly report this action to the Principal Investigator, Department Chair, Institutional Official, the funding agency or study sponsor, if applicable, and other appropriate regulatory authorities.
1. What about elective surgery? This is not expected. Reportable?
NO. Only complications which may be attributed to the study drug(s)/ procedure(s)/ device(s) are reportable as Adverse Events.
2. When does the AE reporting responsibility end?
It is the Principal Investigator’s responsibility to keep the IRB and subjects informed of any changes which may affect a patient’s health or on-going safety even after the study has been completed.
3. When is there a need to update the consent form based on AEs or Unanticipated Problems?
When new information becomes available during the study which may affect the health, safety, or willingness of a participant to continue with the study, the Consent Form should be updated.
4. Why do we need to report Unexpected AEs that are Not Serious?
Office of Human Research Protection (OHRP) requires an IRB to review all “Unanticipated problems” which are inclusive, by definition, of Unexpected Adverse Events. The IRB is also required to review all “Serious” Adverse Events.
IRBs are also responsible for ensuring that reports of unanticipated problems involving risks to human subjects or others are reported to the FDA [21 CFR 56.108(b)(1)]. Usually, this reporting is accomplished through the normal reporting channel, i.e., the investigator to the sponsor to FDA.”
5. The study drug(s) do not show on the Adverse Event Form.
It is possible to submit the Adverse Event report without the study drug(s) listed. The IRB is in the process of updating their systems with all applicable study drug information.
