Kennesaw State UniversityKennesaw State University

Office of Research

Reporting of Unanticipated Problems Involving Risks to Participants and Others

Abstract Lab Work

Researchers encountering a problem or event that is both unanticipated and indicates that 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, must promptly report such problems or events to the IRB. This document provides Office for Human Protections in Research (OHRP) definitions of unanticipated problems and adverse events as well as provides guidance to KSU researchers on how and when to report such problems and events.

Definitions

The following definitions are taken from OHRP’s Guidance on Revising and Reporting Unanticipated Problems Involving Risk to Subjects and Others and Adverse Events, dated January 15, 2007.

  • Adverse event: Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research.
  • External adverse event: From the perspective of one particular institution engaged in a multicenter clinical trial, external adverse events are those adverse events experienced by subjects enrolled by investigators at other institutions engaged in the clinical trial.
  • Internal adverse event: From the perspective of one particular institution engaged in a multicenter clinical trial, internal adverse events are those adverse events experienced by subjects enrolled by the investigator(s) at that institution. In the context of a single-center clinical trial, all adverse events would be considered internal adverse events.
  • Possibly related to the research: There is a reasonable possibility that the adverse event, incident, experience or outcome may have been caused by the procedures involved in the research.
    1. results in death;
    2. is life-threatening (places the subject at immediate risk of death from the event as it occurred);
    3. requires inpatient hospitalization or prolongation of existing hospitalization;
    4. results in a persistent or significant disability/incapacity;
    5. results in a congenital anomaly/birth defect; or
    6. any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse).
  • Unanticipated problem involving risks to subjects or others: Any incident, experience, or outcome that meets all of the following criteria:
    1. unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
    2. related or possibly related to a subject’s participation in the research; and
    3. suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized.
  • Unexpected adverse event: Any adverse event occurring in one or more subjects in a research protocol, the nature, severity, or frequency of which is not consistent with either:
    1. the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol–related documents, such as the IRB-approved research protocol, any applicable investigator brochure, and the current IRB-approved informed consent document, and (b) other relevant sources of information, such as product labeling and package inserts; or
    2. the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.
    Note: For OHRP’s examples of unanticipated problems and adverse events, see Appendices B, C, and D at http://www.hhs.gov/ohrp/policy/advevntguid.html.

Guidance on Reporting

Guidance on reporting

As recommended by OHRP, the following operational details for complying with reporting requirements of HHS regulations at 45 CFR 46.103(b)(5) are provided to assist KSU researchers in reporting unanticipated problems to the IRB.

I. Information for Inclusion in Reports of Unanticipated Problems

The following information must be provided to the IRB:

Study Information
  • a. Study number and name
  • b. Names of all study investigators
  • c. Contact information (phone, email) for all investigators
  • d. Status of study and recruitment: open to accrual; closed to accrual, but participants are still receiving required research intervention; closed to accrual; data analysis is ongoing; other (explain)
Problem/Event Information
  • a. Provide name of subject or subject identifying code
  • b. Provide a detailed description of the problem/event
  • c. Problem/event was (include all that apply):
    • i. Unexpected
    • ii. Related or possibly related (more likely related than unrelated to the research)
    • iii. The research placed or may have placed, subjects or others at a greater risk of physical, psychological, economic or social harm than was previously known or recognized
  • d. Date the PI at KSU recognized/learned of the problem or event; explain any delay in reporting the problem/event to the IRB
  • e. Is problem/event resolved
  • f. Describe the current status of the subject’s participation in the study
  • g. Describe any likelihood that this problem/event was related to the research
  • h. Report any additional information relevant to this problem/event
Corrective Action by the KSU Investigator
  • a. Describe actions taken to address/correct/resolve the problem/event
  • b. Describe actions being implemented to minimize the likelihood of a future recurrence of the problem/event
  • c. Provide copies of relevant reports or correspondence submitted by KSU PI to institutional officials, the sponsor, or any federal officials regarding the problem/event
  • d. In the judgment of the KSU PI, if the occurrence of the problem/event is not consistent with information included in the current, IRB- approved consent form and the frequency and/or severity of the problem/event is not consistent with available published information, describe necessary revisions to the current consent form or protocol
  • e. Describe plans to notify, re-consent, or inform current or past participants of the problem/event (if necessary)

In some cases, requirements for prompt reporting may be met by submitting a preliminary report to the IRB with a subsequent follow-up report being submitted when more information is available. All reporting questions should be directed to the IRB by telephone at (470) 578-2268 or by email at irb@kennesaw.edu.

II. Responsibility for Reporting Unanticipated Problems

KSU’s Assurance of Compliance with the Department of Health and Human Services Regulations for Protection of Human Research Participants states that researchers conducting research under the KSU assurance are to report to the IRB any injuries to human participants, emergency changes in procedure or any unanticipated problems that involve risk to human participants or to others involved in the project. Students or non-faculty staff carrying out projects involving human participants must conform to the policies and procedures within the assurance, but the faculty advisor under whose direction these researchers are working also bears the responsibility to ensure that the responsibilities of those being advised are fulfilled (see KSU Assurance of Compliance).

KSU researchers are directed to correct, as soon as practicable, any problem that has led to an unexpected incident or unfavorable occurrence in order to minimize or prevent additional risks to other human subjects in the research study.

III. Reporting Timeframe

Researchers are to report to the IRB any unanticipated problems that involve risks to human participants or to others involved in the project as indicated:

  • Unanticipated problems that are serious adverse events should be reported to the IRB within 1 week of the investigator becoming aware of the event
  • Any other unanticipated problem should be reported to the IRB within 2 weeks of the investigator becoming aware of the problem

IV. IRB Actions in Response to Reports of Unanticipated Problems

After receiving a report of unanticipated problems involving risks to participants and others, the IRB will make one of the following determinations:

  • Problem/Event does NOT represent an unanticipated problem involving risk to subjects or others. If so, no further action will be taken.
  • Problem/Event does NOT represent an unanticipated problem involving risk to subjects or others, but further action is required.
  • Problem/Event represents an unanticipated problem involving risk to subjects or others. Review by the convened IRB is required unless the risk to subjects or others is minimal.
  • Problem/Event appears to represent serious or continuing non-compliance. Review by the convened IRB is required.

Unanticipated problems determined to be reportable, under OHRP guidelines, will be reported by the Vice President for Research and Graduate Dean or the IRB Chairperson to the appropriate institutional officials, the supporting agency head, and OHRP within one month of the IRB’s receipt of the report of the problem from the investigator.