Unexpected Problem Checklist
*How to determine what needs to be reported to the IRBs and what actions to take regarding unexpected adverse events and problems that place participants or others at greater risk
If the occurrence is reported as an adverse reaction (adverse event according to FDA/OHRP), it is considered unexpected when all of the following criteria are met:
· When an adverse reaction occurs in one or more subjects participating in research where the nature, severity or frequency of the event is not consistent with:
§ Known or foreseeable risk of events associated with the procedures involved in the research and described in the protocol documents, investigator’s brochure, and current informed consent document and other relevant sources of information such as product labeling or inserts;
§ The expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the reaction and their predisposing risk factor profile for the adverse event.
· The adverse reaction is considered related or probably (possibly according to OHRP guidance) related when the event is determined to be at least partially caused by the procedures involved in the research
§ If an event is determined to be solely caused by underlying disease, disorders, or conditions of the participant or other circumstances unrelated to either the research or any underlying disease, then is it not considered related.
· The adverse reaction meets any of the following criteria:
¨ Results in death
¨ Is life threatening (places the participant at immediate risk of death from the event as it occurred
¨ Results in inpatient hospitalization or prolongation of existing hospitalization
¨ Results in persistent or significant disability/incapacity
¨ Results in a congenital anomaly/birth defect, or
¨ Based upon medical judgments, may jeopardize the participant’s health and may require medical or surgical intervention to prevent one of the outcomes listed in this definition
· The unexpected event meets all of the following required criteria:
¨ Unexpected in terms of nature, severity, or frequency given the procedures described in the research protocol and the characteristics of the subject population being studied;
¨ Related or probably related to participation in research (probably related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research;
¨ 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.
· Immediate action is necessary to protect the safety, welfare, or rights of participants or others and the following selected action(s) must be taken:
¨ eliminating the immediate hazard
¨ termination of the research
¨ suspension of research procedures in currently enrolled subjects
¨ suspension of enrollment of new participants,
¨ modification of inclusion or exclusion criteria,
¨ modification of informed consent documents to include newly recognized risks
¨ additional information about the risks to previously enrolled participants will be required.
¨ For multi-site studies, there is an adequate plan to communicate information among the sites because the event may affect the health or safety of the participants or their willingness to continue to participate in the study.
Possible Range of Actions:
Check the required actions below:
¨ Suspension of the research
¨ Termination of the research
¨ Notification of participants when such information may relate to current participants’ willingness to continue to take part in the research or there is a risk to the health or safety of the past or current participants
¨ Request additional information or clarification from the PI and/or data safety monitoring committee
¨ Require changes in the protocol, consent form or other protocol documents
¨ Require current participants to be re-consented to protocol with the changes in the informed consent,
¨ Note the occurrence of the AR/UE, but take no action,
¨ Require a change in the continuing review period,
¨ Require additional monitoring by the IRB,
¨ Request a for-cause audit of the protocol, if not already done, and/or a follow-up audit
¨ Request further inquiry into other protocols utilizing the experimental drug/device/intervention or procedure in question,
¨ Determine if a detailed plan for safe withdrawal of participants from the research must be developed to protect their rights and welfare of participants
¨ Require that this plan be submitted to the IRB for review and approval.
¨ Require that appropriate federal regulatory agencies, sponsors, and institutional officials be notified of any unexpected adverse reactions or unexpected events involving risks to participants or others according to the HIC Policy/Procedure “Reporting Unexpected Events, Continuing or Serious Non-Compliance, and Suspensions and Terminations
¨ No other action required
3/08