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.