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     last updated 6/13/07

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Guidance

taken from the UNIVERSITY OF CHICAGO BSD/UCH IRB POLICIES AND PROCEDURES MANUAL

I. REPORTING POLICY:
(updated 4/2007)

The Food and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) recognize that any adverse event in a trial is a potentially important occurrence because it may reflect additional risks to subjects.  In accordance with their requirements, these regulatory bodies have charged Institutional Review Boards with the responsibility of conducting continuing review of research.  Included in this review is the monitoring of adverse reactions and unexpected events (21 CFR 56.108 and 45 CFR 46.103).  An adverse effect is defined as an undesirable and unintended, although not necessarily unexpected, result of therapy or other intervention.

 In carrying out this responsibility, the University of Chicago BSD/University of Chicago Hospitals IRB adverse event reporting plan requires investigators to assess the adverse event and the relationship of the event to the study.  The reporting policies are dependent upon whether the event occurred at the University of Chicago or a University of Chicago affiliated hospital (see Internal Adverse events) or whether the event occurred at a non-University of Chicago site (see External Adverse events). Definitions are provided below to assist the investigator in determining the seriousness of the event and the relationship of the event to the study. 

A) Internal Adverse events (Events that occur at the University of Chicago or its affiliated hospitals)

Drug/Biologic Studies - Any adverse event that occurs on a research study investigating a drug/biologic and is both serious and unexpected must be reported to the IRB.  In addition, an adverse event may occur which is moderate in severity, not necessarily serious and unexpected, but which in the investigator’s opinion, should be considered by the IRB due to a possible relationship with the drug/biologic being studied.  In both of these cases the adverse event should be reported to the IRB within 10 working days of the investigator’s knowledge of the adverse event.

Device Studies - Any unexpected adverse event that occurs on a device trial (regardless of seriousness) must be reported to the IRB within 10 working days of the investigator’s knowledge of the adverse event.

Any fatal or life-threatening events must be reported to the IRB, in writing, within 48 hours after discovery, regardless of whether or not the event was expected.  Life threatening is defined as the patients being at substantial risk of dying at the time of the adverse event or it is suspected that the use or continued use of the product would result in the patient’s death.  The IRB recognizes that the information pertaining to the event may not be complete at the time of the reporting.  In such cases, this should be reflected in the investigator's assessment and additional information provided when available.

For device studies, the death of a subject who has an experimental device implanted at the time of death should be considered a fatal adverse event and thus reported accordingly, regardless of whether the subject was actively participating in the study at the time.

For drug/biologic studies, the death of a subject is considered a fatal adverse event and thus should be reported as such only if one the following statements apply:  (1) the death occurred within thirty days of last administration of the study drug/biologic or (2) the death is considered possibly related to the study drug/biologic.

B) External Adverse events (Events that occur at non-University of Chicago sites)

Drug/Biologic Studies - Any adverse event that occurs on a research study investigating a drug/biologic and is serious, unexpected, and related or possibly related must be reported to the IRB within 30 working days of the investigator’s knowledge of the adverse event. 

Device Studies - Any unexpected adverse event that occurs on a device trial (regardless of seriousness or causality) must be reported to the IRB within 10 working days of the investigator’s knowledge of the adverse event.

Investigators are required to report adverse events to the study sponsor and  the Food and Drug Administration (for drugs, devices, and biologics). 
 

II. INVESTIGATOR REPORTING PROCEDURES:

It is the responsibility of the investigator to ensure that written notification of such adverse events are submitted to the IRB.  The principal investigator must complete, with his/her original signature, the appropriate IRB adverse event reporting form and attach any additional information necessary in evaluating the report (i.e. autopsy report).  The IRB relies a great deal on the expertise of our investigators to assess the report.  The adverse event report form will require the principal investigator to assess the causality of the event, the seriousness of the event, and whether or not the event was expected.  In addition, the IRB needs the advice of the investigators on whether or not a change in the protocol is necessary to minimize the risks to the subjects, whether the consent form should be revised to reflect this risk, and whether subjects on the study should be reconsented in light of this risk.

A) Internal Adverse events

Serious/Unexpected Adverse Events – Investigators must submit one signed original “Internal Adverse Event Form:  Serious/Unexpected Adverse Events” for each serious and unexpected adverse event (for drug/biologic studies) or unexpected adverse events (for device) studies. 

Fatal/Life-Threatening Adverse Events – Investigators must submit one signed original “Internal Adverse Event Form:  Fatal/Life-Threatening Adverse Events” for each fatal or life-threatening event.

Any adverse events that do not meet the reporting requirements should be summarized at the time of continuing review.

B) External Adverse events

Investigators must submit one signed original “External Adverse Event Form” for any adverse events meeting the criteria for reporting to the IRB (see section I “Reporting Policy” – External Adverse events).  The safety report (a FDA mandated report from the sponsor describing adverse events from different study sites) should be attached to the external adverse event form. 

At the time of continuing review, the Investigator should submit the Data and Safety Monitoring Report or the current annual report to provide the IRB with a summarization of all adverse events that have occurred on the study and the analysis of the events.

In reviewing the adverse event/safety reports, the IRB will consider whether the event impacts the risk/benefit ratio to ensure adequate protection of the welfare of subjects.  Based on the review, the IRB may (1) require modifications to the protocol and/or consent form, (2) revise the continuing review timetable, or (3) reconsider approval of the study.

IV. ADDITIONAL REPORTING REQUIREMENTS:

A written notification of adverse experiences must be submitted to the study sponsor, the Food and Drug Administration (for drugs, devices, and biologics), and the University of Chicago Pharmaceutical Services.  Details of the reporting requirements are described below. 

Adverse events must be reported immediately to the sponsor (except for those events that the protocol or investigator's brochure identifies as not needing immediate reporting).  The sponsor protocol should indicate when and how adverse events are to be reported.  It is likely that the sponsor will require this immediate report be followed promptly by detailed written reports of the event.  Investigators should contact  the study sponsor for specific reporting requirements. 

Pursuant to 21 CFR 312.32, adverse events that are both serious and unexpected must be reported to the FDA.  In the case of industry-sponsored protocols, reporting to the FDA is usually accomplished through the normal reporting channel (i.e. investigator to the sponsoring company to the FDA).  In the case of investigator-initiated research or research that does not involve funding from a sponsoring company, the Principal Investigator of the protocol assumes the responsibility to report adverse events to the FDA.  In such instances, investigators should follow the reporting procedure of the FDA Medical Products Reporting Program (MedWatch).  Under the program, adverse events can be mailed, faxed, or reported online.  The time requirement for MedWatch reporting varies according to the reporting method used (i.e. mailed, phone, faxed, or online).  Additional information on FDA MedWatch reporting can be obtained from the FDA web site http://www.fda.gov/medwatch/index.html.
 

V. DEFINITIONS:

Unexpected AE – An adverse event which is unexpected is one for which the specificity is not consistent with any of the following:

1) Investigator brochure
2) Detailed protocol
3) Risk information in the consent form
4) The reasonably expected natural history and progression of the underlying disease or condition

Serious AE – An adverse event which is serious is one which results in any of the following outcomes:

1) Death
2) A threat to life
3) Inpatient hospitalization or prolongation of existing hospitalization
4) Persistent or significant disability or incapacity
5) Congenital anomaly or birth defect
6) Causes cancer
7) Is an overdose
8) Any medical event which requires treatment to prevent one of the medical outcomes listed above.

Possibly Related – An adverse event which is possibly related is one that may have been caused by the drug, device, or intervention, however there is insufficient information to determine the likelihood of this possibility.