Transcript Adverse Event

Adverse Event/Unanticipated Problems
Policy and Procedures
November 2007
Learning Objectives

Review new Policy and Procedures

Identify what events and problems are
reportable to the IRB

Review some brief case studies
Adverse Event

Any untoward or undesirable experiences
associated with research, including any
abnormal sign (for example, abnormal
physical exam or laboratory finding),
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.
Adverse Event

Adverse events may be the result of:




the interventions and interactions used in
the research
the collection of identifiable private
information in the research
an underlying disease, disorder, or
condition of the subject and/or
other circumstances unrelated to the
research
Adverse Event

Most adverse events are not reportable to
the IRB

The majority of adverse events that occur in
the context of research are expected:



the known toxicities and side effects of the research
procedures
the expected natural progression of the subjects’
underlying diseases, disorders, and conditions, and
subjects’ predisposing risk factor profiles for adverse
events
UCI Adverse Events and
Unanticipated Problems
Policy and Procedures Revisions

Provide expanded list of events reportable to the IRB as
a guide Investigators

Investigator reporting timelines have increased from 48
hours to either 5 or 10 working days

Reduce reporting requirements at time of Continuing
Review – no longer required to submit Adverse Event
(AE, SAE) and Safety Report Summary Log

Report only Unrelated Serious Adverse Events (Deaths)
that occur on UCI IRB approved study at time of
Continuing Review. Use the Internal Unrelated
SAE Summary Log
UCI Adverse Events and
Unanticipated Problems
Policy and Procedures Revisions

If Investigators choose to report deviations and other
non-reportable events (such as expected or unrelated
adverse events) to the IRB, submit the UCI Non
Reportable Events Report to HRP staff for verification.

AE-UP report changes…

No longer required to submit a follow-up report to the IRB
unless the event/problem is not resolved as expected or
the event/problem results in a chronic condition or death

Check box to indicate other entities notified about the
event/problem (e.g., Sponsor, NCI AdEERS, FDA)

Check box to generally describe event/problem
from list of descriptions. Investigator may
choose more than one description
Why the Change?

OHRP Guidance (January 15, 2007)

FDA Guidance (April 9, 2007 draft)

Association for the Accreditation of
Human Research Protections Programs
IRB’s role will be…
To determine whether the event or problem is an
Unanticipated Problem Involving Risk
To Participants Or Others

Unexpected (in terms of nature, severity, or frequency) given (a)
the research procedures that are described in the IRB-approved
documents, such as the protocol and informed consent document,
and (b) the characteristics of the subject population being studied

Related or possibly related to participation in the research
(possibly related means there is a reasonable possibility that the
event or problem may have been caused by the procedures
involved in the research), and

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
If the IRB determines
that the event/problem
is an Unanticipated Problem…
The IRB may take any of the following actions:

Accept the report with no changes

Accept the report with changes to the risk/benefit profile, the protocol, or
the informed consent documents (requires submission of e-MOD
Request)

Require re-consenting of participants

Increase the frequency of continuing review

Impose additional monitoring requirements

Require additional training of the Investigator and research team

Request an “Administrative Hold” pending further information

Suspend or Terminate the study
Case Study #1

A subject enrolled in a Phase 3, randomized, doubleblind, placebo-controlled clinical trial evaluating the
safety and efficacy of a investigational antiinflammatory agent for management of osteoarthritis.

The subject develops severe abdominal pain and
nausea one month after randomization.

Subsequent medical evaluation reveals gastric ulcers.
The IRB-approved protocol and informed consent
document indicated that the there was a 10% chance
of developing mild to moderate gastritis and a 2%
chance of developing gastric ulcers for subjects
assigned to the active investigational agent.
Case Study #1

The investigator concludes that the subject’s
gastric ulcers resulted from the research
intervention and withdraws the subject from
the study.

Should this event/problem be reported to
the IRB?
Case Study #1

Should this event/problem be reported to
the IRB?
NO, although the event is related to the
research intervention, the risk was
foreseeable (described in the IRB-approved
documents) and the subject was not placed at
greater risk of harm than was previously
recognized.
Case Study #2

As a result of a processing error by a pharmacy
technician, a subject enrolled in a multicenter
clinical trial receives a dose of an experimental
agent that is 10-times higher than the dose dictated
by the IRB-approved protocol.

While the dosing error increased the risk of toxic
manifestations of the experimental agent, the
subject experienced no detectable harm or adverse
effect after an appropriate period of careful
observation.

Should this event/problem be reported
to the IRB?
Case Study #2

Should this event/problem be reported to
the IRB?
Yes, the dosing error constitutes a protocol
violation - accidental or unintentional changes to,
or non-compliance with the IRB approved protocol
without prior sponsor and IRB approval. Violations
generally increase risk or decrease benefit, affects
the subject's rights, safety, or welfare, and/or the
integrity of the data
Case Study #3

A subject with seizures enrolls in a randomized, Phase 3 clinical
trial comparing a new investigational anti-seizure agent to a
standard, FDA-approved anti-seizure medication. The subject is
randomized to the group receiving the investigational agent.

One month after enrollment, the subject is hospitalized with
severe fatigue and on further evaluation is noted to have severe
anemia.

The known risk profile of the investigational drug does not
include anemia, and the IRB-approved protocol and informed
consent document for the study do not identify anemia as a risk
of the research.

Should this event/problem be reported to the IRB?
Case Study #3

The known risk profile of the investigational
drug does not include anemia, and the IRBapproved protocol and informed consent
document for the study do not identify anemia
as a risk of the research.

Should this event/problem be reported to
the IRB?
Yes, anemia is (a) unexpected in nature; (b)
possibly related to participation in the
research; and (c) places subjects at greater
risk of harm.
Case Study #4

An investigator conducting behavioral
research collects individually identifiable
sensitive information about illicit drug use and
other illegal behaviors by surveying college
students. The data are stored on a laptop
computer without encryption, and the laptop
computer is stolen from the investigator’s car
on the way home from work.

Should this event/problem be reported
to the IRB?
Case Study #4

Should this event/problem be reported to
the IRB?

Yes, this is a breach in confidentiality that
caused harm or places subjects or others at
a greater risk of harm (including physical,
psychological, economic, or social harm).
Unanticipated Problems…
Under 45 CFR Part 46 and 21 CFR Part 56 the IRB is required to have written
procedures for ensuring prompt reporting to the IRB, appropriate institutional
officials, and the department or agency head of any unanticipated problems
involving risks to subjects or others
UCI IRB is trying to capture events and problems in B and C but not in A
Any questions?
Thanks for listening!