This document provides an overview of new procedures for reporting reportable events at the University of Iowa, effective April 1, 2006. It discusses regulatory reporting requirements for sponsors, investigators, and IRBs for both drug and device studies regulated by the FDA. Key events that require reporting include unanticipated problems involving risks to subjects, serious noncompliance, and suspension or termination of IRB approval. The document defines terms like serious adverse event, unexpected adverse event, and unanticipated adverse device effect as they relate to FDA requirements.

1. Reportable Event?
The University of Iowa
Human Research
Protection Program

2. New Procedures for
Reportable Events
Martha F. Jones, MA, CIP
IRB Chair, (IRB-01/IRB-02) and
Director, Human Subjects Office
Suzanne Bentler, MS
IRB Administrator
Office of the Vice President for Research
The University of Iowa
http://www.research.uiowa.edu/hso/

3. Overview/Key Changes
 April 1, 2006: New procedures begin
 Use of new forms including expanded reporting requirements
 “Old” AE forms in HawkIRB no longer available (except as update
function)
 Projects still in paper will continue to use “old” paper reporting
forms.
 ALL documentation must be submitted in electronic format. We
will no longer accept hard copy documentation for REF forms.
 Unique identifier for each event – you must use the UPDATE
function
 Updated procedures available on HSO website in Investigator’s
Guide (Chapter 7.C):
http://www.research.uiowa.edu/hso/
The University of Iowa
Human Research
Protection Program

4. What are the regulatory
reporting requirements?
 Different requirements for
 Sponsors
 Investigators
 IRBs
 Different requirements depending on type of
study and funding
 FDA
 Drug

Device
 Federal The University of Iowa
 Others? Human Research
Protection Program

5. IRB Reporting Requirements:
DHHS & FDA
 Institution (IRB) must follow written
procedures for prompt reporting to the IRB,
institutional officials, FDA, department/agency
heads of
 Unanticipated problems involving risks to subjects
or others
 Serious or continuing noncompliance with
regulations or the requirements or determinations
of the IRB
 Suspension or termination of IRB approval
The University45 CFR 46.103(b)(5)
DHHS: of Iowa
FDA: 21 CFR 56.108(b)
Human Research
Protection Program

6. Investigator Reporting
FDA – Drug Studies
 21 CFR 312.64(b)
 An investigator shall promptly report to the
sponsor any adverse effect that may
reasonably be regarded as caused by, or
probably caused by, the drug. If the
adverse effect is alarming, the investigator
shall report the adverse effect immediately.
The University of Iowa
Human Research
Protection Program

7. Sponsor Reporting
FDA – Drug Studies
 21 CFR 312.32(c)
 The sponsor shall notify FDA and all participating
investigators in a written IND safety report of:
 (A) Any adverse experience associated with the use of
the drug that is both serious and unexpected; or
 (B) Any finding from tests in laboratory animals that
suggests a significant risk for human subjects including
reports of mutagenicity, teratogenicity, or carcinogenicity.
The University of Iowa
Human Research
Protection Program

8. FDA Drug Definitions
 Associated with the use of the drug
 There is a reasonable possibility that the
experience may have been caused by the
drug
The University of Iowa
Human Research
Protection Program

9. FDA Drug Definitions (continued)
 Serious adverse drug experience
 Any adverse drug experience occurring at any dose that
results in any of the following outcomes:
 Death
 A life-threatening adverse drug experience (immediate risk of
death)
 Inpatient hospitalization or prolongation of existing
hospitalization
 A persistent or significant disability/incapacity
 A congenital anomaly/birth defect
 Important medical events not resulting in the above may be
serious when, based upon the appropriate medical judgment,
they may jeopardize the patient or subject and may require
medical or surgical intervention to prevent oneIowa outcomes
The University of of the
listed above.
Human Research
Protection Program

10. FDA Drug Definitions (continued)
 Unexpected adverse drug experience
 Any adverse drug experience, the specificity or
severity of which is not consistent with the current
investigator brochure or risk information described
in the general investigational plan or elsewhere in
the current application
 Refers to NOT PREVIOUSLY OBSERVED
 Do not interpret as “not anticipated”, for
example based on pharmacological
The University of Iowa
properties Human Research
Protection Program

11. Investigator Requirements
FDA – Device Studies
 21 CFR 812.150(a)(1)
 An investigator shall submit to the sponsor
and to the reviewing IRB a report of any
unanticipated adverse device effect
occurring during an investigation
The University of Iowa
Human Research
Protection Program

12. Sponsor Requirements
FDA – Device Studies
 21 CFR 812.150(b)(1)
 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
The University of Iowa
Human Research
Protection Program

13. FDA Device Definition
 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…or any other
unanticipated serious problem associated with a
device that relates to the rights, safety, or welfare
of subjects. The University of Iowa
Human Research
Protection Program

14. What is NOT Required?
 Immediate reporting of IND safety
reports/outside safety reports UNLESS
 The report itself or the interpretation of the
report by the UI PI represents a change in
the risks or potential benefit associated
with the study

Unanticipated problem (e.g. new risk)
The University of Iowa
Human Research
Protection Program

15. What if Sponsor requires
additional reporting?
 Indicate the IRB does NOT act as the DSMB
for any study
 Policy will be posted on HSO website
 Reports not required by regulation or UI IRB policy
will NOT be accepted by UI IRBs
 Sponsor must provide the federal regulation (not
guidance) for requiring IRB review if disagree
 Summary of non-reportable events may be
The University of Iowa
submitted with Continuing Research
Human
Review
Protection Program

16. The REF Forms
Reportable Event Form
The University of Iowa
Human Research
Protection Program