The Organization requires researchers to comply with all applicable local, state, and federal laws and regulations in the conduct of research studies. As part of this requirement, researchers are required to submit to the JHM IRBs written reports of events that meet the definition of “unanticipated problems involving risks to participants and others.” Problems or events labeled as “unanticipated adverse events” in research involving investigational drugs or devices may or may not meet the definition of an unanticipated problem. Principal investigators (PIs) must report such problems or events to the IRB promptly, as well as to applicable regulatory agencies, sponsors, participating sites (if JHM is the coordinating center) and Institutional Officials.
Death of a JHM research participant may or may not meet the definition of an unanticipated problem or event. Requirements for reporting the death of a JHM participant and the time line for submission of such reports is contained in Policy No. 103.6(b)(i) .
A. “Unanticipated problems involving risks to participants or others” is defined as:
- The information is unexpected in terms of nature, severity, or frequency, given:
a. The research procedures described in the protocol and informed consent document; and
b. The characteristics of the subject population being studied; and
- The information indicates that participants or others are at greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.
B. “Prompt reporting” is defined by the Organization. Prompt reporting of unanticipated problems or events should occur as soon as possible after the PI learns of the event, but in all cases within 10 working days with the exception of death of a JHM participant. Prompt reporting requirements for death of a JHM participant are defined in Policy 103.6(b)(i).
Reportable Problems or Events
The Organization requires prompt reporting of the following unanticipated problems or events:
- Event (including on-site and off-site adverse event reports, injuries, side effects, breaches of confidentiality, or other problems) – occurs any time during or after the research study, which in the opinion of the Principal Investigator (PI):
- Involved harm to one or more participants or others, or placed one or more participants or others at increased risk of harm;
- Is unexpected (an event is “unexpected” when it is not described with specificity in the protocol and informed consent document; or if described with specificity, it occurs beyond the expected frequency and/or severity identified); and
- Is related to the research procedures (an event is “related to the research procedures” if, in the opinion of the principal investigator, it was more likely than not to be caused by the research procedures).
- Information that indicates a change to the risk to benefit ratio of the research. For example:
- An interim analysis indicates that participants have a lower rate of response to treatment than initially expected;
- Safety monitoring indicates that a particular side effect is more severe, or more frequent than initially expected; or
- A paper is published from another study that shows that an arm of the research study is of no therapeutic value.
- Change(s) in FDA labeling or withdrawal from marketing of a “test article” (a drug, device, or biologic) used in a research protocol.
- Change(s) to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a research participant.
- Incarceration of a participant.
- Event that requires prompt reporting to the sponsor.
- Complaint of a participant when the complaint indicates unexpected risks or the complaint cannot be resolved by the research team.
- Protocol violation (a term often used by NIH or commercial sponsors, meaning an accidental or unintentional change to the IRB approved protocol) that placed one or more participants at increased risk, or has the potential to occur again.
- An unanticipated adverse device effect as defined by FDA at 21 CFR Part 812.3(s).
- If the JHM IRB reviewed the research study under ICH-GCP guidance (E6), then the PI is responsible for reporting to the JHM IRB:
- New information that may affect adversely the safety of the participants or the conduct of the clinical trial; and
- Any changes significantly affecting the conduct of the clinical trial or increasing the risk to participants.
Form of Report
A written report of the unanticipated problem or event is to be submitted by the PI to the IRB in eIRB by using the Further Study Action activity, and submitting a Problem/Event Report or for paper studies, submitting a Problem/Event Report Form R.F.1. Reports may be accepted by other means such as e-mail or phone only if the report is of an urgent nature. If the report is made by phone, the PI is still obligated to submit a written report as soon as possible to the IRB.
Review of Problem or Event Reports
The Organization requires review of unanticipated problem or event reports. Each reported problem or event will be assessed to determine if it meets the definition of an unanticipated problem involving risks to participants or others. Review of a problem or event may require use of a consultant, or assistance from the division or department chair to collect additional information before a determination is made. Action will be taken to address the problem. The actions may be taken by the Institutional Official, other senior Organization officials charged with taking action, or the IRB. The range of actions includes items listed below, but the list does not preclude taking additional actions as determined on a case-by-case basis:
- Administrative hold on the study pending IRB receipt of further information from the PI in a time period not to exceed 90 days;
- Modification of the protocol;
- Modification of the information disclosed during the consent process;
- Providing additional information to current participants (this must be done whenever the information may relate to the participant’s willingness to continue participation);
- Making arrangements for clinical care outside the research or additional follow-up for participants;
- Providing additional information to past participants;
- Requiring current participants to re-consent to participation;
- Alteration of the frequency of continuing review;
- Observation of the research or the consent process;
- Requiring additional training of the investigator and/or study team members;
- Notification of investigators at other sites;
- Obtaining additional information;
- Termination or suspension of the research. Such action will be reported to the Institutional Official (IO).
The IO will be informed when a determination has been made that a problem or event meets the definition of an unanticipated problem involving risks to participants or others. The IO will fulfill the requirements to report the action to federal departments or agencies as required by regulation in accord with Policy 103.6(a).
If a determination is made that a problem or event does not meet the definition of an unanticipated problem involving risks to participants or others, no further action needs to be taken and a report to the IO is not required.