Reporting Responsibilities of the Investigator

Procedure for Submission of RNI

The electronic online submission process must be utilized to submit an RNI. The smart form questions will collect specific information required for review by the IRB. The IRB Researcher’s Quick Reference Guide available in the PittPRO Help Center includes instructions for submission.

Reporting Responsiblities of the Investigator

Outlined below are the requirements for reporting to the University IRB. 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.

General Reporting Requirements for Reportable Non-Compliance:

Unless subject to different IRB reporting requirements by a federal agency, investigators must report to the University IRB incidents that may meet the definitions of Serious and/or Continuing Non-compliance within 10 working days of the Investigator’s knowledge of the Reportable Non-Compliance.

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

• Accidental or intentional deviation from the IRB-approved protocol that involves potential serious risks (e.g., missed safety labs, incorrect dosing, or labeling).
• Performing non-exempt human subject research without obtaining prospective IRB approval.
• Implementing protocol modifications without obtaining prospective IRB approval.
• Failure to follow 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• Obtaining consent using an outdated consent form when the new consent form contained new information that may have caused the subject to change their mind about participating.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.

Requirements for Incidents of Non-Compliance that are Not an RNI:

Incidents of Non-compliance which are unlikely to meet the definition of Serious and/or Continuing Non-compliance do not need to be reported to the IRB but should be logged in real time and made available upon request. Non-compliance/deviation logs are not required to be submitted at annual review but must be available upon request. The IRB expects that the Investigator and study team will regularly monitor the Non-compliance/deviation log. An example of a Non-compliance/deviation log is available on the Education & Compliance Support for Human Subject Research (ECS-HSR) website.

Non-Compliance/deviation logs are mandatory for:

• Greater than minimal risk studies;
• Studies that meet the federal definition of a clinical trial; or
• Studies for which reporting is required by the funding agency.

Non-compliance/deviation logs are recommended, but not mandatory for all other studies.

Examples of Non-compliance that are not reportable to the IRB but should be documented on a Non-compliance/deviation 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., administering a questionnaire outside of the protocol specified window).

General Reporting Requirements for Adverse and Other Events That May Be an Unanticipated Problems Involving Risk to Human Subjects or Others:

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

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.

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 the Investigator’s knowledge 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.)

External Adverse Events that may meet the above definition must be reported to the University IRB within 30 working days of their receipt by the University/UPMC investigator. (Note: Only sponsor-generated safety reports that meet the above Adverse Event reporting requirement should be submitted to the University IRB).

Ideally, Adverse Events occurring in subjects enrolled in a multicenter study should be submitted to a monitoring entity for review and analysis before submitting to the IRB.

The RNI submission of the Adverse Event to the University IRB should include confirmation as to whether the external site reported the event to their IRB and/or to a monitoring entity.

The External Adverse Event reported to the University IRB may be placed on a committee agenda for review as determined by the IRB Chair or designee.

• Deviation from the protocol taken without prior IRB review to eliminate apparent immediate hazard to a given research subject.
• 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.
• A subject complaint or concern that indicates an unanticipated risk or cannot be resolved by the research staff. An 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).
• An untoward event that presents a risk to Investigators and research staff involved in the conduct of the research.

These events must be reported to the IRB within 10 working days of the investigator’s knowledge of the event.

See Chapter 26 for specific federal agency reporting requirements.

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 University IRB. Expected Adverse Events or Adverse Events determined by the Investigator to be unrelated to the research intervention do not need to be reported to the University 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.

Adverse Events which are unlikely to meet the definition of an Unanticipated Problem Involving Risk to Human Subjects or Others do not need to be reported to the IRB but should be logged in real time and made available upon request. The maintenance of an adverse event log is mandatory for studies if the Principal Investigator is also the sponsor of an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application, or if it is required by the funding agency. It is recommended for all other clinical trials. The IRB expects that the Investigator and study team will regularly monitor the Adverse Event log. An example of an Adverse Event log is available on the ECS-HSR website.

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 and the 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 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 FDA should occur as soon as possible but no later than 7 working days following the sponsor’s initial receipt of the information.
   
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 IBC 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 FDA should occur as soon as possible but no later than 15 working days following the sponsor’s initial receipt of the information.
   
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) and the IRB. If the sponsor of the human gene transfer research study is a University investigator, reporting of the follow up information to the FDA should occur as soon as possible but no later than 15 working days following the sponsor’s receipt of the information.
   
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 adverse event should be reported promptly to the external sponsor (if applicable) and the IRB. If the sponsor of the human gene transfer research study is a University investigator, reporting of this Adverse Event information to the FDA should occur as soon as possible but no later than 15 working days following the sponsor’s receipt of the information.
   
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 adverse event should be reported promptly to the external sponsor (if applicable) and the IRB. If the sponsor of the human gene transfer research study is a University investigator, reporting of the adverse event to the 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 any of the above reports to the FDA.

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