SUBJECT: Ensuring Prompt
Reporting of Unanticipated Problems Involving Risks to Participants or Others
PURPOSE: To ensure that the organization promptly reports unanticipated problems involving risks to participants or others to the IRB, regulatory agencies, and appropriate institutional officials.
POLICY: This procedure is followed whenever a the IRB office learns problem, regardless of whether the problem is reported by the investigator or the IRB office learns about the problem by other mechanisms.
SCOPE: This
policy covers all research protocols conducted within the auspices of this
Institutional Review Board (IRB).
RESPONSIBILITIES:
Principal Investigator (PI) is responsible to report to the IRB the problems that require prompt reporting.
DEFINITIONS:
“Adverse Event” is any reaction or undesirable event that occurs in conjunction with the use of a drug, biologic product, diagnostic agent, medical device, experimental procedure, or even accepted medical treatment or procedure (if part of a research protocol), whether or not the event is considered related to the drug treatment or procedures. Such events may be psychological, emotional, social, or physical and include any illness, sign, symptom, or clinically significant laboratory test abnormality that has appeared or worsened during the course of the experimental study regardless of causal relationship to the drugs and procedures under study. For observational studies (e.g., chart reviews, data base studies, surveys), deaths, life-threatening events or hospitalizations need not be reported as AEs. Any AE directly or indirectly related to the study, such as loss of confidentiality or emotional trauma are still reportable. In addition, reports of subjects having complaints about the experimental procedures or about the conduct of the investigators may be reported as AEs.
PROCEDURE:
Investigators must report to the IRB the following problems as soon as possible, but always within the described time frames:
(Note: These are not unanticipated problems involving risks to participants or others. These are the problems that the IRB wants promptly reported to ensure that among the reported problems will be the problems that are unanticipated problems involving risks to participants or others. The IRB, not the investigator, decides which of the reported problems are unanticipated problems involving risks to participants or others.)
1. Any harm experienced by a participant (including any adverse event) regardless of whether the event was internal (on-site) or external (off-site) and regardless of whether the event meets the FDA definition of “serious adverse event”), which in the opinion of the principal investigator are both unexpected and related. Indicate that adverse events not meeting these criteria do not need to be reported.
a. A harm is “unexpected” when its specificity and severity are not accurately reflected in the informed consent document.
b. An harm is “related to the research procedures” if in the opinion of the principal investigator, it was more likely than not to be caused by the research procedures or if it is more likely that not that the event affects the rights and welfare of current participants).
2. Information that indicates a change to the risks or potential benefits of the research should be reported no later than 10 calendar days from occurrence or discovery. For example:
a. An interim analysis or safety monitoring report indicates that frequency or magnitude of harms or benefits may be different than initially presented to the IRB.
b. A paper is published from another study that shows that the risks or potential benefits of your research may be different than initially presented to the IRB.
3. A breach of confidentiality should be reported no later than 10 calendar days from occurrence or discovery.
4. Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a research protocol should be reported no later than 10 calendar days from occurrence or discovery.
5. Change to the protocol taken without prior IRB review to eliminate apparent immediate hazard to a research participant should be reported no later that 10 calendar days from occurrence or discovery.
6. Incarceration of a participant in a protocol not approved to enroll prisoners should be reported no later than 10 calendar days from occurrence or discovery.
7. Event that requires prompt reporting to the sponsor should be reported no later that 10 calendar days from occurrence or discovery.
8. Complaint of a participant when the complaint indicates unexpected risks or cannot be resolved by the research team should be reported no later than 10 calendar days from occurrence or discovery.
9. Protocol violation that caused harm to participants or others or indicates that participants or others are at increased risk of harm should be reported no later than 5 calendar days from occurrence or discovery.
10. DSMB reports.
11. Unanticipated adverse device effect (Any serious adverse effect on health or safety or any life-threatening 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 plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.)
All reported problems will be reviewed by the IRB Chair or his/her designee. The reviewer will be provided the Adverse Event and Other Problem Report Checklist and the study file (if necessary). This reviewer will determine and document whether the reported problem is an unanticipated problem involving risks to participants or others based on whether the event is both:
· Unforeseen
· Caused harm or placed participants at increased risk of harm.
If the reviewer determines that the event is an unanticipated problem involving risks to participants or others, he/she will require review by the convened IRB. If the reviewer determines that the event is not an unanticipated problem involving risks to participants or others, no further considerations or actions are required.
The convened IRB will make a determination as to whether each event is an unanticipated problem involving risks to participants or others and this will be reflected in the minutes of the meeting. If the convened IRB determines that the event is not an unanticipated problem involving risks to participants or others, no further considerations or actions are required. All IRB members will receive a copy of the AE/SAE Report Form, any materials the investigator sent, and the reviewer’s comments.
The range of actions to be considered by the convened IRB, include:
· Modification of the research protocol
· Modification of the information disclosed during the consent process
· Providing additional information to past participants
· Notification of current participants when such information may relate to participants' willingness to continue to take part in the research
· Requirement that current participants re-consent to participation
· Modification of the continuing review schedule
· Monitoring of the research
· Monitoring of the consent
· Suspension of the research
· Termination of the research
· Referral to other organizational entities
The Director, ORI will report to institutional officials and regulatory agencies when the IRB determines that a problem is an unanticipated problem involving risks to participants or other. See Reporting Policy SOP for information on reporting procedures.
FOLLOW-UP
RESPONSIBILITY: Director, Office of
Research Integrity
REFERENCES: 21 CFR 56.108(b)(1); 21 CFR 312.32(a)(1); 45
CFR Part 46, Subpart A
Revised 5-1-2007
