Chapter 17 - Reportable Events

During the conduct of human subjects research, unanticipated events may occur. These events must be reported to the IRB using the “Reportable Events” mechanism in OSIRIS. While the smart form questions within the OSIRIS application will assist investigators in determining the type of report required, a general summary is provided in the paragraphs below and in figure 1.

Events involving risk to human subjects or others must be reported as an “Unanticipated Problem Involving Risk to Human Subjects or Others”. This category includes some types of adverse events meeting the definition of an unanticipated problem involving risk to human subjects or others. This category can also include protocol deviations, non-compliance, or other unanticipated problems that place subjects at risk of harm. Examples include but are not limited to: missed safety labs, medication or dosing errors, potential breaches of confidentiality, etc.

Protocol deviations and incidents of non-compliance, which do NOT involve risk to human subjects or others must be reported as “Non-compliance”. Examples include but are not limited to performing research procedures outside the protocol specified window, deviating from the protocol without risk to the subject, obtaining consent using an outdated consent form with no other substantive differences other that the date, etc.

Figure 1. Reportable Events summary

Reportable event flow chart

Figure 2. Venn Diagram summarizing the general relationship between adverse events, unanticipated problems, and non-compliance

Reportable event venn diagram

Figure 2 illustrates several key points:

  • The vast majority of adverse events occurring in human subjects are not unanticipated problems (area A) and do not need to be reported to the IRB.
  • Only a small proportion of adverse events are unanticipated problems (area B).
  • Unanticipated problems include other incidents, experiences, and outcomes that are not adverse events (area C).
  • Deviations or non-compliance can also be unanticipated problems involving risk to subjects or others.
  • Events meeting criteria for an Unanticipated Problem Involving Risk to Subjects or Others, or Non-compliance (Areas B, C D and E) must be reported to the IRB.

Management and Reporting of Unanticipated Problems Involving Risks to Human Subjects and Others and Non-compliance

It is the policy of the University of Pittsburgh Institutional Review Board (University IRB) to:

  • Require the reporting of adverse events and other unanticipated events which meet the definition of an “unanticipated problem involving risks to human subjects or others” and/or Non-compliance
  • Review reports of adverse events, unanticipated problems and ECO-HSR compliance activity reports that have been designated for review by the IRB as outlined in the ECO-HSR policy (SOP-I-A-15) , and determine which meet the OHRP criteria for “unanticipated problems involving risks to human subjects or others”
  • Review reports of non-compliance and determine which constitute serious or continuing non-compliance and/or an unanticipated problem involving risk to human subjects or others
  • Fulfill reporting requirements to the appropriate entities (institutional officials, federal departments or agencies)

Reportable Event Definitions

Adverse event: An unfavorable medical occurrence, which may include abnormal signs (for example, abnormal physical exam or laboratory finding), symptoms, or disease, temporally associated with, but not necessarily considered related to, the subject’s participation in the research study.  Not all adverse events meet IRB reporting guidelines.

Continuing non-compliance: Non-compliance that has been previously reported or a pattern of ongoing non-compliance that, in the judgment of the University IRB, significantly adversely affects the rights and welfare of participants or significantly compromises the quality of the research data.

External adverse event: An adverse event that occurs at a site external to the authority of the University IRB and is reported to the University or UPMC investigator.

Internal adverse event: An adverse event that occurs at a site that falls directly under the authority of the University IRB.

Non-compliance: Failure on the part of the investigator or any member of the study team to follow the terms of University of Pittsburgh IRB approved protocol or to abide by applicable laws or regulations, or University of Pittsburgh IRB policies. This includes protocol deviations. This also includes ECO-HSR compliance activity reports that have been designated for review by the IRB as outlined in the ECO-HSR policy (SOP-I-A-15). The IRB will determine whether reports meet the definition of serious or continuing non-compliance.

Incidents of noncompliance on the part of research participants which do not involve risk need not be reported to the IRB.

Possibly Related to the Research Intervention: In the opinion of the principal investigator, there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research.

Related to the Research Intervention: In the opinion of the principal investigator, the incident, experience or outcome more likely than not was caused by the procedures involved in the research.

Serious non-compliance: Non-compliance that, in the judgment of the University IRB, significantly adversely affects the rights or welfare of participants, or significantly compromises the quality of the research data.  Examples of non-compliance that are considered to meet the definition of serious non-compliance include, but are not limited to:

  1. performing non-exempt human subject research without obtaining prospective University IRB approval
  2. implementing substantial modifications to a research study without obtaining prospective University IRB approval
  3. failing to systematically obtain research subjects’ informed consent as required by the IRB approved protocol
  4. failing to comply with federal regulations governing human subject protections (this includes activities of the University IRB and/or University IRB Office staff)

Unanticipated: Unforeseeable at the time of its occurrence.

Unanticipated Problem Involving Risks to Human Subjects or Others: Any accident, experience, or outcome that meets all of the following criteria:

  1. unexpected in terms of nature, severity, or frequency;
  2. related, or possibly related, to a subject’s participation in the research;
  3. places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Unexpected Adverse Event: Not identified by nature, severity or frequency in the investigator’s brochure, sponsor protocol or current University IRB-approved research protocol or informed consent document, taking into account the characteristics of the subject population being studied.

Reporting Responsibilities of the Investigator

Adverse Events That Are Unanticipated Problems Involving Risk To Subjects Or Others - General Reporting Requirements

Outlined below are the requirements for reporting to the IRB. Note that investigators may have additional reporting obligations as specified by the study sponsor or oversight agency. Investigators who serve as sponsor-investigators of an IND or IDE also have additional reporting obligations to the FDA.

Unless subject to different IRB reporting requirements by a federal agency, investigators must report to the IRB:

  1. Internal Adverse Events that are (i) Unexpected, (ii) Related or Possibly Related to the Research Intervention, and (iii)serious or otherwise suggests that the research places the subject or others at a greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized.
     
  2. External Adverse Events that are (i) Unexpected; (ii) Related to the Research Intervention and (iii) Serious or otherwise suggests that the research places subjects or others at greater risk than was previously recognized.

Please note that the vast majority of Adverse Events will not meet the definition of an Unanticipated Problem Involving Risk to Subjects or Others, and need not be reported to the IRB. Expected Adverse Events or Adverse Events which are determined by the investigator to be unrelated to the Research Intervention will not be reviewed by the IRB. The flow chart below provides an algorithm for determining whether an adverse event meets the definition of an unanticipated problem involving risk to subjects or others.

Figure 3. Reporting requirements summary

General IRB Reporting Timelines

Adverse Events that meet the University IRB’s reporting requirements must be reported to the IRB office as follows:

  1. Internal Adverse Events which are unexpected, fatal or life-threatening, and related or possibly Related to the Research Intervention must be reported to the IRB within 24 hours of learning of the event. (Note: It is recognized that the information available during this 24 hour period may not be sufficient to permit accurate completion of the required adverse event reporting forms. However, the IRB should, at a minimum, be notified of the fatal or life-threatening internal adverse event during this time frame, with subsequent followup submission of a more detailed written report.)
     
  2. All other internal Adverse Events will be reported to the IRB within 10 working days of the investigator learning of the event.
     
  3. External Adverse Events which are Unexpected, Serious AND suggest that the research places subjects or others at greater risk than was previously recognized, and Related to the Research Intervention will be reported to the IRB within 30 working days of their receipt by the University/UPMC investigator. (Note: only sponsor-generated safety reports that meet the Adverse Event reporting of the IRB should be submitted to the IRB.)

Special Reporting Requirements - Gene Transfer Interventions

All Unexpected, Serious Internal Adverse Events related to the gene transfer intervention must be reported to the external sponsor of the research study (if applicable) and to the IRB, Institutional Biosafety (rDNA) Committee, NIH Office of Biotechnology Activities (OBA), and Food and Drug Administration using the following criteria:

  1. Unexpected, fatal or life-threatening internal Adverse Events related or possibly related to the gene transfer intervention must be reported to the external sponsor (if applicable), IRB and Institutional Biosafety (rDNA) Committee within 24 hours of learning of the event. If the sponsor of the human gene transfer research study is a University investigator, reporting of the adverse event to the OBA and FDA should occur as soon as possible but no later than 7 working days following the sponsor’s initial receipt of the information. (If the human gene transfer research study is externally sponsored, it is the responsibility of the external sponsor to report the adverse event to the OBA and FDA.)
     
  2. Unexpected, Serious (but not fatal or life-threatening) Internal Adverse Events Related or Possibly Related to the gene transfer intervention, must be reported to the external sponsor (if applicable), IRB and Institutional Biosafety (rDNA) Committee as soon as possible but no later than 5 calendar days of the reaction. If the sponsor of the human gene transfer research study is a University investigator, reporting of the adverse event to the OBA and FDA should occur as soon as possible but no later than 15 working days following the sponsor’s initial receipt of the information. (If the human gene transfer research study is externally sponsored, it is the responsibility of the external sponsor to report the adverse event to the OBA and FDA.)
     
  3. Any follow up information related to an Unexpected, Serious Adverse Event Related or Possibly Related to a gene transfer intervention should be reported promptly to the external sponsor (if applicable), IRB, and Institutional Biosafety (rDNA) Committee. If the sponsor of the human gene transfer research study is a University investigator, reporting of the follow up information to the OBA and FDA should occur as soon as possible but no later than 15 working days following the sponsor’s receipt of the information. (If the human gene transfer research study is externally sponsored, it is the responsibility of the external sponsor to report the follow up information to the OBA and FDA.)
     
  4. If an Unexpected, Serious Adverse Event occurs after the end of the clinical trial and it is determined to be related or possibly related to the gene transfer intervention, the reaction should be reported promptly to the external sponsor (if applicable), IRB, and Institutional Biosafety (rDNA) Committee. If the sponsor of the human gene transfer research study is a University investigator, reporting of this Adverse Event information to the OBA and FDA should occur as soon as possible but no later than 15 working days following the sponsor’s receipt of the information. (If the human gene transfer research study is externally sponsored, it is the responsibility of the external sponsor to report this adverse event information to the OBA and FDA.)
     
  5. If, after further evaluation, an Unexpected, Serious Internal Adverse Event initially considered not to be related to the gene transfer intervention is determined to be Related, then the Unexpected, Serious Internal Adverse Event should be reported promptly to the external sponsor (if applicable), IRB, and Institutional Biosafety (rDNA) Committee. If the sponsor of the human gene transfer research study is a University investigator, reporting of the adverse event to the OBA and FDA should occur as soon as possible but no later than 15 working days of this determination. (If the human gene transfer research study is externally sponsored, it is the responsibility of the external sponsor to report this determination to the OBA and FDA.)

The above reporting requirements apply to all research studies involving gene transfer interventions regardless of the source of the research funding.

Procedure for Submission

OSIRIS SUBMISSIONS: For studies approved through the electronic submission system, the “Reportable Event” online submission process must be utilized in order to submit a report. The smart form questions will prompt a response to questions related to the adverse event.

PAPER SUBMISSIONS: Adverse Events for paper studies will also be individually reviewed by the full-board IRB. Submit the following by email to askirb@pitt.edu:

  • IRB Cover Sheet marked “Adverse Event Report” and, if applicable, “Modification;”
  • Completed IRB Adverse Event Form and a narrative summary of the event;
  • Completed sponsor adverse event reporting form or FDA MedWatch report form (For gene transfer interventions, the completed NIH Office of Biotechnology Activities (OBA) Serious Adverse Event Report Form);
  • Modification request form (if applicable);
  • IRB Approved Protocol, with modifications highlighted;
  • IRB approved informed consent document, with modifications highlighted;
  • Consent Form Addendum to provide new information to currently enrolled subjects (if applicable).

"Other" Unanticipated Problems Involving Risk to Subjects or Others and Non-compliance

Unanticipated problems which meet the following definition of “any accident, experience or outcome” that meets the following criteria must be reported:

  • unexpected in terms of nature, severity, or frequency;
  • related, or possibly related, to a subject’s participation in the research;
  • places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized;

Examples of types of unanticipated problems that must be reported to the IRB include:

  • any accidental or intentional deviation from the IRB-approved protocol that involves risks (e.g., missed safety labs, incorrect dosing or labeling);
  • any deviation from the protocol taken without prior IRB review to eliminate apparent immediate hazard to a given research subject;
  • any publication in the literature, safety monitoring report, interim result, or other finding that indicates an unexpected increase in the risk to benefit ratio of the research;
  • any complaint of a subject that indicates an unanticipated risk or which cannot be resolved by the research staff;
  • any other untoward event that affects the welfare or the privacy, confidentiality or other rights of research subjects or members of their family (e.g. lost or stolen research data);
  • any other untoward event that presents a risk to investigators and research staff involved in the conduct of the research.

Incidents of non-compliance, which meet the following must be reported: Failure on the part of the investigator or any member of the study team to follow the terms of University of Pittsburgh IRB approval or to abide by applicable laws or regulations, or University of Pittsburgh IRB policies. This includes protocol deviations. Incidents of noncompliance on the part of research participants which do not involve risk need not be reported to the IRB (i.e., failure to turn in medication diary).

Examples of non-compliance that must be reported to the IRB include:

  • Performing non-exempt human subject research without obtaining prospective University IRB approval;
  • Implementing protocol modifications without obtaining prospective IRB approval;
  • Altering from the informed consent process as described in the IRB approved protocol;
  • Obtaining consent using an outdated consent form;
  • Conducting research during a lapse in IRB approval;
  • Failing to adhere to the IRB approved protocol due to action (or inaction) of the investigator or staff (i.e., protocol deviations)Not -adhering to inclusion/exclusion criteria;
  • Enrolling more subjects that approved in the protocol;
  • Performing research procedures outside the protocol specified window;

Failure on the part of any individual involved in research review or oversight to abide by applicable laws or regulations, or University of Pittsburgh IRB policies.

General Reporting Requirements

Investigators are to submit all Unanticipated Problems Involving Risks to Human Subjects or Others that are Possibly or Definitely Related to the research and incidents of Non-compliance within 10 working days of the investigator becoming aware of the event.

Submission Format for Reporting Other Unanticipated Problems Involving Risks to Human Subjects or Others and incidents of Non-Compliance

OSIRIS SUBMISSIONS: For studies approved through the electronic submission system, the Reportable Event online submission process must be utilized in order to submit a report. The smart form questions will prompt a response to questions related to the Unanticipated Problem or Non-compliance.

PAPER SUBMISSIONS: Investigators are required to submit reports utilizing the form entitled “Report of Unanticipated Problems Involving Risks to Subjects or Others and Non-compliance,” which is available on the IRB website.

 

Responsibilities of the Education and Compliance Office for Human Subject Research

The Education and Compliance Office for Human Subject Research is responsible for reporting to the IRB Chair and Adverse Events Coordinator any compliance activity report that may represent serious non-compliance, continuing non-compliance or an unanticipated problem involving risks to human subjects or others as outlined in ECO-HSR SOP = I-A-15.

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

 

 

Parties Responsible for Preparation and Distribution of Correspondence

Internal Adverse Events

Correspondence surrounding adverse events reviewed at the IRB meeting will be drafted by the AEC and approved by the IRB Chair or Vice Chair. The IRB Chair or Vice Chair will ensure the report is distributed to all applicable parties.

Study Termination or Suspension

For studies in OSIRIS, the IRB Chair or his designee will suspend or terminate the study within the system. Correspondence is sent to the Principal Investigator as well as to all listed co-investigators and research staff. The study moves to a “suspended” or “terminated” state and the consent documents are no longer accessible. For paper studies, reports surrounding study termination or suspension will be drafted by the IRB staff and approved by the IRB Chair or Vice Chair. The IRB Chair or Vice Chair will ensure the report is distributed to all applicable parties.

Serious or Continuing Non-Compliance and Unanticipated Problems Involving Risks to Human Subjects or Others

Correspondence related to determinations of serious or continuing non-compliance or that involve risk to subjects related to ECO-HSR compliance report activities will be prepared by the Co-Director of the RCCO or his/her designee for approval by the IRB Chair and Associate Legal Counsel.

Correspondence related to determinations of serious or continuing non-compliance or that involve risks to human subjects or others related to unanticipated problems will be drafted by the Research Review Coordinator (RRC) for review and approval by the Co-Director of the RCCO, the IRB Chair and Legal Counsel.
After review and comment by the above parties, the Authorized Institutional Official will review, approve and sign the report and ensure the report is distributed to all applicable parties.

Compliance Activity Reports

Correspondence related to Compliance Activity Reports where the study remains active and no serious or continuing non-compliance were identified or protocol modifications were required will be prepared by the Education and Compliance Office staff for signature of the Co-Director of the Research Conduct and Compliance Office.

Correspondence related to a Compliance Activity Report which resulted in a determination of serious or continuing non-compliance; an unanticipated problem involving risks to human subjects or others; or study termination or suspension will be performed in the same manner as other determinations of this kind.

When a protocol modification is necessary as the Compliance Activity Report, the correspondence associated with the protocol modification will be drafted by the IRB staff with input from the Education and Compliance Office for signature by the IRB Chair or Vice Chair.

Recipients of the IRB Correspondence/Reports

Investigator Correspondence

The University IRB Chair or Vice Chair communicates the IRB’s determinations to the principal investigator. If the IRB’s decision requires immediate action on the part of the principal investigator, the decision will be communicated verbally to the principal investigator as soon as possible and followed up with written notification by the IRB Chair or Vice Chair within 10 working days of the decision.

A date for the investigator response is specified in the written notification. Failure to comply with this date, in the absence of a suitable justification, will be handled in accordance with University IRB policies involving the reporting and handling of other unanticipated problems.

Compliance of the principal investigator with the directed actions specified by the reviewing University IRB committee are reviewed and approved by the IRB Chair or an IRB Vice Chair unless full board review of the principal investigator’s response/actions is determined to be required by the reviewing University IRB committee.

If the principal investigator has additional information that may be relevant to the situation at hand, it will be brought to the attention of the reviewing University IRB committee for consideration.

Institutional Official, Regulatory Agencies, Sponsors and Others

In addition to the IRB correspondence sent to the investigator, reports of any unanticipated problems involving risks to human subjects or others, any serious or continuing non-compliance, any suspension or termination of IRB approval will be sent to all applicable parties, which may include:

  • The Office for Human Research Protections – for research funded by any agency that is a signatory to the “Common Rule” at 45 CFR 46;
  • The Food and Drug Administration – for research that is subject to the FDA regulations at 21 CFR 50 and 56;
  • The federal or non-federal external funding agency For DOD funded research, the letter will be sent to the attention of the Director, Defense Research and Engineering;
  • The VAMC R&D Committee and the regional VA Office of Research Oversight;
  • The UPMC Office for Sponsored Programs and Research Support;
  • Other University offices (e.g., Office of Research, Conflict of Interest, Risk Management);
  • The principal investigator;
  • The department chair;
  • University or UPMC legal counsel;
  • University or UPMC risk management;
  • UPMC Institutional Officials.

References