Responsibilities of the IRB

Internal and External Adverse Events

Internal Adverse Events (IAE) and External Adverse Events (EAE) reported to the University IRB are received and processed promptly by the Regulatory Affairs Specialist, or in his/her absence, by a designated University IRB research review coordinator.

Adverse events that meet the University IRB’s definition of an “unanticipated problem involving risk to human subjects or others” may be brought to the attention of the University IRB Chair or, in his/her absence, a University IRB Vice Chair by the Regulatory Affairs Specialist. In processing adverse events that appear to meet the University’s definition of an unanticipated problem involving risks to human subjects or others, the Regulatory Affairs Specialist will:

  • Place the events on the agenda for review at the next convened University IRB meeting where there is a member with appropriate expertise. If there are potential risks to subjects which require action prior to a convened meeting, an emergency meeting may be convened (with the members attending either in person or via teleconference) or in exceptional safety circumstances, the chair has the authority to suspend some or all of the research activities. When this authority is exercised by the Chair, it will be reported at the next convened University IRB meeting.
  • Perform a retrospective review of adverse events reported for the research protocol. If the adverse event was reported by the investigator as being related to a research intervention, then an assessment of the adverse events across other research protocols involving the same experimental intervention will be performed.
  • Make an initial determination as to whether protocol and/or consent form modifications are required to address the reported adverse event. In making this determination, the Regulatory Affairs Specialist will take into consideration the severity of the event, the number of reports describing the same or similar event, and the current consent form and research protocol risk statements.

"Other" Unanticipated Problems Involving Risk to Subjects or Others

  • Unanticipated problems received or identified by the University IRB Office are brought to the attention of the University IRB Chair, or in his absence, a University IRB Vice Chair.
  • The University IRB Chair (or Vice Chair) will determine if the report of an unanticipated problem contains complete information that will allow an adequate review for human subject protections. If, in the opinion of University IRB Chair (or Vice Chair), the information is incomplete, s/he may request appropriate additional information from the individual submitting the report.
  • The University IRB Chair (or Vice Chair) will determine if the reported unanticipated problem may involve a risk to human subjects or others or non-compliance with the federal regulations or the requirements or determinations of the University IRB.
  • Unanticipated problems that may represent an “unanticipated problem involving risks to human subjects or others,” “serious noncompliance” or “continuing non-compliance” as defined above, will be referred to a convened University IRB committee.
  • For those reports that clearly do not represent either i) an unanticipated problem involving risks to human subjects or others, ii) serious non-compliance, or iii) continuing non-compliance, the University IRB Chair or designee will determine if any additional actions are warranted and, if applicable, will communicate that in writing to the individual who initiated the report.
  • The unanticipated problem report, the determination of the University IRB Chair (or Vice Chair), and a record of the requested actions, if applicable, will be documented in the IRB file.
  • Failure to comply with actions requested by the University IRB Chair (or Vice Chair), in the absence of a suitable justification, constitutes an unanticipated problem of non-compliance and be brought to the attention of a convened University IRB committee.

Management of Research Participant Complaints

It is the policy of the University of Pittsburgh IRB to investigate all complaints or concerns reported by study participants to the IRB.

All consent documents must include telephone numbers for the principal investigator and the Human Subject Protection Advocate so that participants can call if they have questions, concerns or complaints.

The IRB will investigate all participant complaints received and will complete the Documentation of Patient/Subject Complaint Form. Actions taken to resolve complaints might include referring the complaint to:

  • the Human Subject Protection Advocate;
  • the Principle Investigator;
  • completion of “reportable event;”
  • the IRB Committee F.

The IRB Office maintains files of research subject complaints and the actions taken by the IRB Office staff, IRB Committee(s), or investigators to resolve such complaints. Such files are maintained until 3 years following termination of IRB approval of the research study.

Non-compliance with the protocol

  • Reports of non-compliance with the protocol received or identified by the University IRB Office will be reviewed by the Adverse Events Coordinator, who will triage the reports.
  • The Regulatory Affairs Specialist determines if the report of non-compliance with the protocol contains complete information that will allow an adequate review for human subject protections. If, in the opinion of Regulatory Affairs Specialist, the information is incomplete, s/he may request appropriate additional information from the individual submitting the report.
  • The Regulatory Affairs Specialist will refer to the IRB Chair all reports where the reported non-compliance with the protocol that may involve a risk to human subjects or others or serious or continuing non-compliance with the federal regulations or the requirements or determinations of the University IRB.
  • The University IRB Chair (or Vice Chair) determines if the reported non-compliance with the protocol may involve a risk to human subjects or others or non-compliance with the federal regulations or the requirements or determinations of the University IRB.
  • Reports of non-compliance with the protocol that may represent an “unanticipated problem involving risks to human subjects or others,” “serious noncompliance” or “continuing non-compliance” as defined above, will be referred to a convened University IRB committee.
  • For those reports of non-compliance with the protocol that clearly do not represent either i) an unanticipated problem involving risks to human subjects or others, ii) serious non-compliance, or iii) continuing non-compliance, the University IRB Chair or designee determines if any additional actions are warranted and, if applicable, communicates that in writing to the individual who initiated the report.
  • The report of non-compliance with the protocol, the determination of the University IRB Chair (or designee), and a record of the requested actions, if applicable, will be documented in the IRB file.
  • Failure to comply with actions requested by the University IRB Chair (or designee), in the absence of a suitable justification, constitutes a report of non-compliance and be brought to the attention of a convened University IRB committee.

Distribution of Information, Reviewer Assignment and Presentation to a Convened IRB Committee

Adverse Events that are Unanticipated Problems

All members of the convened committee will have access to the following:

  • the adverse event report;
  • the IRB-approved research protocol and consent documents;
  • the recommendations of the Regulatory Affairs Specialist.

Each adverse event will be assigned to two primary reviewers with relevant scientific expertise.

The primary reviewers will summarize the adverse event and their decision regarding concurrence with the actions recommended by the Regulatory Affairs Specialist or, in the event of disagreement, propose alternate actions. After the presentation from the primary reviewers, all members of the convened committee will be given the opportunity to comment on the recommendations.

Other Unanticipated Problems and Non-compliance

All members of the convened Committee will have access to the following:

  • all available documentation regarding the reported unanticipated problem;
  • the IRB-approved research protocol and consent documents, if necessary;
  • the ECO-HSR compliance activity report, the investigator’s response to the report and the unanticipated problem reports submitted to the IRB as a result of the ECO-HSR review of the protocol as applicable.

No primary reviewer system will be utilized for reviewing "Other" unanticipated problems or Non-compliance.

The Education and Compliance Office will summarize ECO-HSR compliance activity reports for the Committee. All other cases of non-compliance will be summarized by the IRB Chair or Vice Chair. All members of the convened committee will be given the opportunity to comment on the recommendations.

Possible IRB Committee Actions

The reviewing Committee takes whatever actions are deemed necessary to address the unanticipated problem(s). Examples of actions that might be taken include, but are not limited to:

  1. Investigating the Event by:
    • requesting additional records or information about the event and its outcome;
    • interviewing the involved investigators, research staff, and/or research subjects;
    • interviewing other individuals who may have knowledge of the event;
    • requesting an independent audit of the event/protocol or of other related protocols.
  2. Implementing Administrative Actions, such as:
    • requesting the IRB Chair (or Vice Chair) to meet with the involved investigator and/or research staff, and the appropriate department chair and/or dean to discuss the event/problem;
    • requesting a corrective plan of action and/or written standard operating procedures from the involved investigator and/or his/her department chair or dean;
    • requiring members of the research team to participate in pertinent training and education programs;
    • notifying other organizational entities (e.g., legal counsel, institutional risk management, the Authorized Institutional Official, the Research Integrity Officer, the UPMC Clinical Trials Office, UPMC Privacy Officer) as warranted;
    • suspending the PI’s privilege to serve as a PI or requiring a replacement of the PI for the protocol(s) in question.
  3. Requiring Modifications of the Associated Protocol, such as
    • instructing the investigator to develop an addendum consent form to provide information concerning the event to subjects currently enrolled in the study;
    • requiring the investigator to perform additional follow-up or monitoring of the enrolled subjects;
    • revising the timeframe for continuing University IRB review.

    For multi-center studies - if the IRB or the local investigator proposes changes to the protocol or informed consent document/process, in addition to those proposed by the study sponsor or the coordinating center, the IRB should request in writing that the local investigator discuss the proposed modifications with the study sponsor or coordinating center and submit a response or necessary modifications for review by the IRB.

  4. Terminating or Suspending University IRB Approval of the Research Study

    When terminating or suspending some or all research activities, the University IRB will consider what additional actions the principal investigator or institution should take in order to protect the rights and welfare of current human subjects. These additional actions may include but are not limited to:

    • Transferring the human subjects to another research study (i.e., based on equivalent inclusion/exclusion criteria);
    • Making arrangements for clinical care outside the research;
    • Allowing continuation of some research activities under the supervision of an independent monitor;
    • Requiring or permitting follow-up of the human subjects for safety reasons;
    • Requiring adverse events or outcomes to be reported to the University IRB and the sponsor;
    • Notifying current human subjects of the University IRB’s decision to terminate or suspend the research study;
    • Notifying former human subjects of the University IRB’s decision to terminate or suspend the research study;
  5. Requiring other action as determined to be appropriate by the University IRB committee.
  6. Requiring no further action.

IRB Vote and Documentation in the Meeting Minutes

The University IRB will determine the recommended actions, call for a vote and document the outcome in the Committee minutes. The University IRB votes as to whether the event represents an unanticipated problem involving risks to human subjects or others, serious non-compliance and/or continuing non-compliance. This vote will be recorded in the meeting minutes. If the University IRB votes to suspend or terminate the research study, the reasons for the suspension or termination will be documented.

Communication of IRB decisions

Please see Reporting of IRB Determinations, Chapter 18.

References

•    45 CFR 46.103(b)(5)
•    21 CFR 56.108(b) (1), 312.53 (c) (vii) and 312.66 – Investigators are required to report promptly to the IRB all unanticipated problems involving risks to human subjects or others
•    OHRP - Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events
http://www.hhs.gov/ohrp/policy/advevntguid.html
•    Appendix M – NIH Guidelines for Research Involving Recombinant DNA Molecules
•    Standard Operating Procedures for the Education and Compliance Office for Human Subject Research
http://www.ecohsr.pitt.edu/regulatory-information/.
 

version 12.10.2015