PROMPT
REPORTING OF UNANTICIPATED PROBLEMS INVOLVING RISKS TO
SUBJECTS OR OTHERS
PURPOSE
The purpose of this policy is to define the requirements
for prompt reporting to the Partners Human Research Committees
(PHRC) of any unanticipated problems involving risks to
subjects or others.
This
policy is established to comply with Department of Health
and Human Services (DHHS) regulations at 45 CFR 46.103(b)(5)
and 45 CFR 46.108(a) requiring IRBs 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.” The Food and Drug Administration
regulations include the same requirement [21 CFR 56.108(b)(1)].
Additionally,
federal regulations 45 CFR 46.113 and 21 CFR 56.113 state,
“IRBs shall have the authority to suspend or terminate
approval of research that is not being conducted in accordance
with the IRB’s requirements or has been associated with
unexpected serious harm to subjects.” To exercise this
important authority in a timely manner, IRBs must be informed
promptly of any problem that is unexpected and related
(or possibly related) to participation in the research,
and that places subjects or others at greater risk of
harm than was previously known or recognized. Therefore,
once the research is approved by the PHRC, investigators
covered by this policy are required to report unanticipated
problems to the PHRC, as described in this document.
SCOPE
All investigators conducting non-exempt human research
who rely on the PHRC for IRB review are subject to this
policy.
UNANTICIPATED
PROBLEMS
Although federal regulations require prompt reporting
to the IRB of any unanticipated problems involving risks
to subjects or others, the phrase is not defined in either
HHS or FDA regulations. In January 2007, the Office for
Human Research Protections (OHRP) released new guidance
to assist IRBs in fulfilling this requirement. According
to the guidance document OHRP considers unanticipated
problems, in general, to include any incident, experience,
or outcome that meets all of the following criteria:
-
unexpected (in terms of nature, severity, or frequency)
given (a) the research procedures that are described
in the protocol-related documents, such as the IRB-approved
research 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 incident, experience, or outcome 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.
Adverse
Events
When the incident, experience, or outcome involves any
untoward or unfavorable medical occurrence in a human
subject, 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, the incident is considered an adverse
event and is subject to the PHRC Adverse Event Reporting
Policy.
Other Incidents, Experiences or Outcomes
Not all incidents, experiences or outcomes involving harm
to subjects are adverse events. Some incidents involve
social or economic harm, rather than physical or psychological
harm. When such incidents occur, the investigator is responsible
for assessing whether the incident, experience, or outcome:
(1) is unexpected; (2) is related or possibly related
to participation in the research; and (3) 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.
Examples
of other incidents, experiences, or outcomes that may
meet the definition of unanticipated problems involving
risks to subjects or others include:
-
Participant complaints
-
Laboratory errors
-
Medication errors
-
Procedural errors
-
Unauthorized disclosure of confidential information
-
Lost or stolen confidential information
-
Disqualification of investigators
-
Suspension of investigators
ASSESSING
INCIDENTS, EXPERIENCES OR OUTCOMES
Determining
whether a particular incident, experience, or outcome
is unexpected and whether it is related or possibly related
to participation in the research may be difficult. When
making this assessment, the investigator should take into
consideration whether substantive changes in the research
protocol or informed consent document, or other corrective
actions may be warranted in order to protect the safety,
welfare, or rights of subjects or others. Generally, when
substantive changes are proposed to minimize the risk
of harm to subjects, the problem is considered an
unanticipated problem involving risks to
subjects or others that requires prompt reporting to the
PHRC.
For
examples of unanticipated problems that do not involve
adverse events and need to be reported under the HHS regulations
at 45 CFR 46, refer to Appendix B of the OHRP Guidance
on Reviewing and Reporting Unanticipated Problems Involving
Risks to Subjects or Others and Adverse Events.
REQUIREMENTS
FOR PROMPT REPORTING OF UNANTICIPATED PROBLEMS
Serious Unanticipated Problems Involving Risks
to Subjects or Others
All unanticipated problems involving risks to subjects
or others that are serious must be reported to the PHRC
as soon as possible, but in no event later than 10 working
days/14 calendar days of the date the investigator first
becomes aware of the problem or event.
Serious unanticipated problems are those incidents, experiences,
or outcomes that place subjects at increased risk of serious
physical or psychological harm, (e.g., events that result
in death; a life-threatening experience; inpatient hospitalization
or prolongation of hospitalization; disability or incapacity;
congenital anomaly/birth defect; or any other event that
may jeopardize the subject’s health and may require medical
or surgical intervention to prevent one of these outcomes);
or any significant economic or social harm (e.g., events
that result in criminal or civil liability, damage to
financial standing, employability, insurability, reputation,
or are stigmatizing).
Note: Changes made in approved research to eliminate
an apparent immediate hazard to subjects must be reported
within 24 hours.
Unanticipated Problems Involving Risks to Subjects or
Others that are Not Serious
All unanticipated problems involving risks to subjects
or others that are not serious must be reported to the
PHRC within 20 working days/30 calendar days of the date
the investigator first becomes aware of the problem or
event.
For reporting purposes, investigators are asked to complete
and submit the PHRC Unanticipated Problem Form. When as
a result of the problem, changes are proposed to the research
protocol and/or the informed consent document, investigators
are also asked to complete and submit the PHRC Amendment
Form together with the Unanticipated Problem Form.
REQUIREMENTS
FOR REPORTING UNANTICIPATED PROBLEMS AT CONTINUING REVIEW
At
continuing review, the PHRC must ensure that the criteria
for IRB approval under HHS regulations at 45 CFR 46.111
and, when applicable, FDA regulations at 21 CFR 56.111
continue to be satisfied. Investigators will be asked
to provide a summary of any unanticipated problems that
occurred since the last IRB review.
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