Reporting Unanticipated Problems Involving Risk to Subjects or Others and Adverse Events

1. Reporting Unanticipated Problems Involving Risk to Subjects or Others and Adverse Events WFUHS Policy/Procedure Effective Date 6/1/07 Wendy Murray Monitoring and Oversight Specialist Office of Research

2. Revised WFUHS Policy This revised policy is intended to help ensure that the review and reporting of unanticipated problems and adverse events to the WFUHS IRB occur in a timely, meaningful way so that human subjects can be better protected from avoidable harms while reducing unnecessary burden.

3. Unanticipated Problems Any event, incident, experience, or outcome involving risk to subjects or others that meet the following criteria: 1- Unexpected 2- Related or possibly related to participation in the research 3- Places subject at a greater risk of harm than previously known or recognized

4. Adverse Event Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign, 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

5. Adverse events encompass both physical and psychological harms. They occur most commonly in the context of biomedical research, although on occasion, they can occur in the context of social and behavioral research.

6. AE = Unanticipated Problem To determine whether an adverse event is an unanticipated problem, the following questions should be asked: • Is the adverse event unexpected? • Is the adverse event related or possibly related to participation in the research? • Does the adverse event suggest that the research places subjects or others at a greater risk of harmthan was previously known or recognized? Answer to all three questions is yes= an unanticipated problem and must be reported!

7. The first step in assessing whether an adverse event meets the third criterion for an unanticipated problem is to determine whether the adverse event is serious. A serious adverse event is any adverse event that: • results in death; • is life-threatening (places the subject at immediate risk of death from the event as it occurred);

8. results in inpatient hospitalization or prolongation of existing hospitalization; • results in a persistent or significant disability/incapacity; • results in a congenital anomaly/birth defect; or • 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

9. the research places subjects or others at a greater risk of physical or psychological harm than was previously known or recognized. • warrant substantive changes in the research protocol or informed consent process/document or other corrective actions in order to protect the safety, welfare, or rights of subjects or others

10. Site’s Reporting Requirements GOLDEN RULE: 7 CALENDAR DAYS (of becoming aware of the event) Internal events And/or External events

11. Review of events reported to the IRB M/O specialist reviews and will forward for IRB review which will determine the following: 1- Proposed response is appropriate to ensure safety, rights, and welfare of subject 2- Risk to subjects are minimized (1- using procedures consistent with sound research design; 2- using procedures already being performed on subjects for treatment or diagnostics) 3- Risk to subjects are reasonable in relation to benefit 4- The research plan makes adequate provision for monitoring the data collected to ensure the safety of the subjects

12. IRB Reporting Requirements Any event, incident, experience, outcome that the WFUHS IRB determines to be an unanticipated problem involving risk to subjects or others occurring at a site approved by WFUHS IRB and occur in a study supported by DHHS or other federal agencies that have adopted 45 CFR 46 will be reported to the Office of Human Research Protections (OHRP)

13. Other reporting requirements PI and study team are responsible for meeting other reporting requirements such as: Sponsor Other study sites Coordinating center Data safety monitoring committee All which may be specified in the study protocol, contract, grant, etc.

14. OHRP website reflecting new guidance: http://www.hhs.gov/ohrp/policy/AdvEvntGuid.htm Monitoring & Oversight 716-6928