Reporting Responsibilities of the Investigator

Adverse Events That Are Unanticipated Problems Involving Risk To Human Subjects Or Others

General Reporting Requirements for Adverse Events

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 1) Unexpected, 2) Related or Possibly Related to the Research Intervention, and 3) 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 1) Unexpected, 2) Related to the Research Intervention and, 3) Serious or otherwise suggests that the research places subjects or others at greater risk of harm (including physical, psychological, economic or social harm) than was previously recognized or recognized.

Please note that the vast majority of Adverse Events will not meet the definition of an Unanticipated Problem Involving Risk to Human 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 do not need to be reported to 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 Human Subjects or Others.

                              

General IRB Reporting Timelines for Adverse Events

Adverse Events that meet the definition of an Unanticipated Problem Involving Risk to Human Subjects or Others must be reported to the IRB as follows:

Internal Adverse Events

  • 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 follow-up submission of a more detailed written report.)
  • All other internal Adverse Events that meet the definition of an Unanticipated Problem Involving Risk to Human Subjects or Others will be reported to the IRB within 10 working days of the investigator learning of the event.

External Adverse Events

  • External Adverse Events which are Unexpected, Serious 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).
  • Ideally, Adverse Events occurring in subjects enrolled in a multicenter study should be submitted to a monitoring entity for review and analysis. 
  • The report of the adverse event to the IRB should include confirmation as to whether the external site reported the event to their IRB and to a monitoring entity.
  • The external adverse event reported to the IRB may be placed on a Committee agenda for review as determined by the IRB Chair/Vice Chair.
  • The IRB may act with regard to the local study in response to the external adverse event (e.g., suspend the local study enrollment, but will not report the event to a federal agency or sponsor unless required by the local action).

Special Reporting Requirements for Adverse Events Involving Gene Transfer Interventions

All Serious Internal Adverse Events related or possibly 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 Committee (IBC) NIH Office of Science Policy (NIH), and Food and Drug Administration (FDA) 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 Committee (IBC) 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 IBC, NIH 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 NIH and FDA.)
  1. 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 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 NIH 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 NIH and FDA.)
  1. 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 Committee (IBC). If the sponsor of the human gene transfer research study is a University investigator, reporting of the follow up information to the NIH 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 NIH and FDA.)
  1. 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 Committee (IBC). If the sponsor of the human gene transfer research study is a University investigator, reporting of this Adverse Event information to the NIH 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 NIH and FDA.)
  1. 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 Committee (IBC). If the sponsor of the human gene transfer research study is a University investigator, reporting of the adverse event to the NIH 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 NIH 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 of Reportable New Information

The electronic online submission process must be utilized to submit Reportable New Information (RNI). The smart form questions will collect specific information required for review by the IRB.  Investigators can find detailed information regarding the reporting process in the A-Z Guidance

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

  1. Unanticipated Problems Involving Risk to Human Subjects or Others that meet all three of the following criteria must be reported:

  • Unexpected in terms of nature, severity, or frequency; AND
  • Related, or possibly related, to a subject’s participation in the research; AND
  • 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 Involving Risk to Human Subjects or Others that must be reported to the IRB include (but are not limited to):

  • Any accidental or intentional deviation from the IRB-approved protocol that involves potential serious 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 or concern of a subject that indicates an unanticipated risk or 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.

 

  2. Incidents of Reportable Non-compliance that 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 IRB approved study application or to abide by applicable laws or regulations, or HRP policies that may:

  • Significantly adversely affect the safety, rights, or welfare of human subjects; OR
  • Significantly compromise the quality or integrity of the research data (i.e., negatively impacts the ability to draw conclusions from the study data); OR
  • Represent Continuing Non-compliance (i.e., has been previously reported or represents a pattern of ongoing non-compliance).

Examples of Non-compliance that must be reported to the IRB include (but are not limited to):

  • Performing non-exempt human subject research without obtaining prospective IRB approval.
  • Implementing protocol modifications without obtaining prospective IRB approval.
  • Altering from the informed consent process as described in the IRB-approved study application.
  • Obtaining consent using an outdated consent form when the new consent form contained new information that may have caused the subject to change their mind about participating.
  • Conducting research during a lapse in IRB approval.
  • Not adhering to inclusion/exclusion criteria.
  • Enrolling more subjects than were approved in the protocol of a greater than minimal risk study.
  • Failure on the part of HRP staff involved in research review or oversight to abide by applicable laws or regulations, or HRP policies.

 

   3. Incidents of Non-compliance that are not required to be reported:

Incidents of Non-compliance (including Non-compliance on the part of the research participant) that do not meet the IRB reporting requirements for reporting should be logged in real time and made available upon request. An example of a Non-compliance/deviation log is available on the HRP website.  The IRB expects that the Investigator and study team will regularly monitor the Non-compliance/deviation log. 

Non-Compliance/deviation logs are mandatory for:

Non-compliance/deviation logs are not required to be submitted at annual review but must be available upon request. Non-compliance/deviation logs are recommended but non-mandatory for all other studies.

Examples of Non-compliance that are not reportable but should be documented in a log include (but are not limited to):   

  • Obtaining consent using an outdated consent form when there were no substantive differences between the consent form that was used and the consent form that should have been used (i.e., dates in the footer);
  • Protocol deviations that do NOT adversely affect the safety, rights or welfare of human subjects or significantly compromise the quality or integrity of the research data;
  • Subject Non-compliance that does not involve risk or compromise the quality or integrity of the research data;
  • Performing non-safety related research procedures outside the protocol specified window (i.e., involuntarily administering a questionnaire outside of the protocol specified window).

General Reporting Requirements for Unanticipated Problems Involving Risk to Human Subjects or Others and Non-Compliance:

Investigators are to submit all Unanticipated Problems Involving Risks] to Human Subjects or Others and incidents of Reportable Non-compliance within 10 working days of the Investigator becoming aware of the Reportable New Information.   

5/14/2021