Boston University
Charles River Campus IRB
Policies and Procedures

Title:
Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events
Date: May 31, 2016

Purpose

The purpose of this policy is to outline the procedure for reporting and reviewing unanticipated problems involving risks to subjects or others and adverse events.

Defined Terms

Unanticipated Problem Involving Risks to Subjects or Others: Any incident, experience or outcome that is: 1) unexpected (in terms of nature, severity, or frequency) given the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and the informed consent document, and the characteristics of the subject population being studied, 2) related or possibly* related to 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) than was previously known or recognized.

*Possibly related means that there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research

Adverse Event: Any untoward or unfavorable physical or psychological 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.

Serious Adverse Event: Any adverse event that: 1) results in death, 2) is life-threatening (places the subject at immediate risk of death from the event as it occurred), 3) results in 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) 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.

Unexpected Adverse Event: Any adverse event occurring in one or more subjects participating 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 associate with the procedures involved in the research that are described in (a) the protocol-related documents, such as the IRB-approved 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 underling disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.

Unexpected Adverse Device Effect: Any serious adverse effect on health or safety or any lifethreatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of the subjects

Additional Requirements for studies subject to FDA Regulations:

  • Investigational Devices (IDE): A sponsor who conducts an evaluation of an unanticipated adverse device effect under 21 CFR 812.46(b) shall report the results of such evaluation to FDA and to all reviewing IRB’s and participating investigators within 10 working days after the sponsor first receives notice of the effect.
  • Bioequivalence/Bioavailability: When conducting bioequivalence or bioavailability studies, the person conducting the study must notify FDA and all participating investigators of any serious adverse event, as defined in 21 CFR 312.32(a), observed during the conduct of the study as soon as possible but in no case later than 15 calendar days after becoming aware of its occurrence
  • Investigational New Drugs (IND): The sponsor must notify FDA and all participating investigators (i.e., all investigators to whom the sponsor is providing drug under its INDs or under any investigator’s IND) in an IND safety report of potential serious risks, from clinical trials or any other source, as soon as possible, but in no case later than 15 calendar days after the sponsor determines that the information qualifies for reporting.

Policy

Federal regulations require that the IRB have written procedures to ensure prompt reporting of any unanticipated problems involving risks to subjects or others to the IRB, appropriate institutional officials, and the department or agency head.

The following events must be reported to the IRB within 5 working days of discovery:

  • Death of a research subject if the death is related or possibly related to the research study
  • Adverse events that are unanticipated (in terms of nature, severity, or frequency, related or possibly related, and suggest that there is an increased risk to subjects or others than was previously known
  • Any event or problem that is unanticipated (in terms of nature, severity, or frequency, related or possibly related, and suggest that there is an increased risk to subjects or others than was previously known
  • Breach of confidentiality
  • Suspension or termination of the research study by the Sponsor or other agency
  • Incarceration of a research subject enrolled into the study  Study staff misconduct
  • Medication or laboratory error regardless of whether subjects experienced harm
  • New information (e.g. interim analysis, safety monitoring report, publication, or other finding) that suggests that there are new or increased risks to subject or others
  • A complaint by a research subject or others that suggests that rights, welfare, or safety of a subject has been adversely affected
  • Any other problem that suggests that the research places subjects or others at an increased risk for harm or adversely affects the rights, welfare or safety of subjects or other

The IRB will make a determination if the unanticipated problem constitutes serious and/or continuing noncompliance.

Procedures

Submission of Unanticipated Problem/Adverse Event:

  1. The Principal Investigator is responsible for submitting the unanticipated problem/adverse event using the Event Form. Unanticipated problems and adverse events that are unexpected and related must be reported within 5 working days upon discovery.
  2. The Principal Investigator must submit all unanticipated problems and adverse events to the Sponsor and other applicable agencies as required; reports to Federal oversight bodies will be handled by the IRB Office.

Screening of Submissions:

  1. The unanticipated problem/adverse event is received by the IRB Coordinator and screened for completeness. If information is missing, the IRB Coordinator will request the missing information from the Principal Investigator.

Determining Review Type (Expedited vs. Full Board):

  1. The IRB Coordinator forwards the unanticipated problem/adverse Event Form to the IRB Director for review. The IRB Director confirms the completeness and accuracy of the form and then forwards to the IRB Chair or Vice-Chair for review.
  2. The IRB Chair/Vice-Chair and IRB Director makes a determination whether the event meets the definition of an unanticipated problem involving risks so subjects or others.
  3. If the event does not meet the definition of an unanticipated problem involving risks to subjects or others, the IRB Chair/Vice-Chair and IRB Director conducts the review using expedited procedures.
  4. If the event meets the definition of an unanticipated problem involving risks to subjects or others, it will be referred to the full board for review.
  5. If the IRB Chair/Vice-Chair and IRB Director are unable to determine if the event is an unanticipated problem involving risks to subjects, it will be referred to the full board for review.
  6. If additional expertise is needed, the IRB Director will contact the appropriate IRB member for consultation.

Expedited Review Procedure for Unanticipated Problem/Adverse Event:

  1. If the event is determined to not meet the definition of an unanticipated problem involving risks to subjects or others, the IRB Chair/Vice-Chair will review the event using expedited procedures. The review will be documented by the use of the appropriate reviewer checklist.
  2. The IRB Chair/Vice-Chair will determine the appropriate corrective action plan.
  3. The Principal Investigator will be notified of the determination and corrective action plan via letter.
  4. All reported events will be reported to the full board at the next convened meeting.

Full Board Review Procedure for Unanticipated Problem/Adverse Event:

  1. If the event is determined to be unanticipated problem involving risks to subjects or others by the IRB Chair/Vice-Chair and IRB Director, the event will be reviewed by the full board.
  2. The IRB Chair/Vice-Chair and IRB Director will assign the event to an IRB Member(s) for review. The review will be documented by the use of the appropriate reviewer checklist.
  3. The assigned reviewer will present the event at the full board.
  4. The assigned reviewer and all IRB members attending the meeting will receive the following materials as applicable:
    • Event Form
    • Correspondence regarding the event
    • IRB Application
    • Informed Consent Form
    • Event Reviewer Checklist
    • Other materials related to the event and/or to the investigation of the event
  5. The full board will review the event, determine if the event meets the definition of an unanticipated problem involving risks to others, and determine the appropriate corrective action. Corrective actions may include:
    • Education
    • Modifications to the protocol
    • Notification of current and/or past subjects
    • More frequent IRB review
    • Additional monitoring
    • Prohibit use of study data
    • Suspension
    • Termination
  6. If the event is determined to be an unanticipated problem involving risks to subjects and others it will be reported as outlined in the “Reporting Policy.”
  7. The IRB will also determine if the event meets the definition of serious and/or continuing non-compliance.
  8. If the event meets the definition of serious and/or continuing non-compliance it will be processed as outlined in the “Noncompliance Policy” and “Reporting Policy.” 5
  9. The Principal Investigator will be notified of the determination and correction action plan via letter.

Subject Complaints

Subject complaints that are not submitted to the IRB using an Event form are reported/forwarded to the IRB Director. The IRB Director will investigate the complaint including contacting the subject as appropriate. The complaint will then be handled in accordance with the process described above beginning with ‘Determining Review Type’.

Title: Unanticipated Problems Involving Risks to Subjects or Others & Adverse Events

Author: Cynthia Monahan

Effective Date: October 1, 2012

Last Review/Update:

Date: May 31, 2016

Revision #: 3

Approved:
Cynthia Monahan, IRB Director
Kathryn Mellouk, Associate Vice President-Research Compliance

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