*Forms are subject to change. Check for the latest forms on the Tulane IRB web site.
Reporting Guidelines
Tulane University Human Research Protection Program
Protocol Deviation/Violation/Exception, and Lapsed IRB Approval Reporting Guidelines
Protocol Deviations
A protocol deviation (“Protocol Deviation”) is any change or alteration from the procedures stated in the
study protocol, consent document, recruitment process, or study materials (e.g. questionnaires) originally
IRB approved. Protocol Deviation is a general term and includes, Protocol Exceptions, changes made to
avoid immediate harm to subjects, and Protocol Violations. Protocol Deviations can be examples of noncompliance, either non-serious or serious.
Protocol Violation:
A protocol violation (“Protocol Violation”) is a subset of Protocol Deviation. It is any planned or unintended
changes or deviations from the IRB approved study protocol, consent document, recruitment process, or
study materials that were not approved by the IRB prior to implementation. Generally, Protocol Violations
occur after the subject is enrolled in the Research. However, some Protocol Violations, such as deviations
from the approved consent process, can occur before the subject is enrolled in the research. Protocol
Violations may be either Major Protocol Violations or Minor Protocol Violations, based on their relative
severity.
Major Protocol Violation:
A major protocol violation (“Major Protocol Violation”) is a deviation that has an impact on subject safety,
may substantially alter risks to subjects, may have an effect on the integrity of the study data, or may affect
the subject’s willingness to participate in the study. Major Protocol Violations can vary in the degree of
seriousness according to how the changes impact subject safety, the degree of noncompliance with Federal
regulations, State laws, the HRPP, Tulane policies or procedures, and the degree of foreknowledge of the
event. Major Protocol Violations are reportable events and must be submitted to the Tulane University IRB
within 5 working days of the researcher becoming aware of the event.
Examples of Major Protocol Violations include:
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Failure to obtain informed consent from the subject;
Failure to obtain valid informed consent (e.g., obtained verbal consent when IRB requires signed
informed consent);
Enrolling a subject who does not meet the inclusion and exclusion criteria;
Performing study procedures that have not been approved by the IRB;
Failure to perform a required laboratory test or procedure that could impact upon the safety of the
subject;
Continuing research activities after IRB approval has expired;
Use of recruitment procedures that have not been approved by the IRB;
Enrolling significantly more subjects than was proposed to and approved by the IRB;
Enrollment of a subject from a federally-defined vulnerable population (i.e. children, pregnant
women, prisoners) without prior IRB approval for that vulnerable population.
1
Issued: 9/24/09
Effective: 9/24/09
Form #: 704
Last Reviewed: 9/24/09
Last Revised: 9/24/09
*Forms are subject to change. Check for the latest forms on the Tulane IRB web site.
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Reporting Guidelines
An Investigator deliberately decides to follow a different procedure than that set forth in the
protocol for one or more subjects (other than to eliminate apparent immediate hazards to the
subject or others);
Loss of laptop computer that contained identifiable, private information about subjects;
Accidental distribution of incorrect study medication;
Investigator realizes that a diagnostic blood test was not described in the protocol but is needed to
regulate serum levels of the study drug;
The protocol indicates that a research coordinator will conduct in-take interviews and review the
consent document with subjects. The research coordinator retires so a clinic nurse does the
procedure instead; and
Sponsor belief that study data to date indicates a potential participant could safely participate but
does not meet currently approved eligibility criteria.
Minor Protocol Violation:
A minor protocol violation (“Minor Protocol Violation”) is one that does not impact subject safety,
compromise the integrity of the study data, or affect the subject’s willingness to participate in the study.
Minor Protocol Violations are reportable events and must be submitted to the Tulane University IRB
within 10 working days of the researcher becoming aware of the event.
Examples of Minor Protocol Violations include:
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Use of unapproved recruitment procedures or materials (e.g., when slightly altered);
Inappropriate consent process documentation (e.g., dated by someone other than the subject,
missing signature of person obtaining consent, incorrect date on consent);
Use of expired or outdated consent document (i.e., it does not affect the safety of the subject,
integrity of the study, or subject’s willingness to participate in the Research);
Study visits outside the protocol-prescribed visit window (e.g., the subject is on vacation or is 1
week late for a visit due to illness);
Failure of the subject to return unused study medication; and
Enrollment numbers that exceed specifications.
Planned Protocol Deviations (Exceptions):
Note: Planned protocol deviations (Exceptions) that may adversely affect the rights, safety or welfare of
subjects or the integrity of the research data should be submitted to Tulane IRB for review and approval prior
to implementation except where necessary to eliminate apparent immediate hazards to the human subjects
[(DHHS 45 CFR § 46.103(b)(4); (FDA 21 CFR § 56.108(a)(4); ICH 3.3.7]. Use the Tulane IRB Protocol
Deviation/Violation Report for review and approval of a planned protocol deviation (Exception) prior to
implementation of the changes.
Lapsed Research (expired date of IRB approval of research). Tulane IRB shall conduct continuing review
of research at intervals appropriate to the degree of risk, but not less than once per year [DHHS 45 CFR §
46.109(e)]. If the IRB approval date has expired, and the research is in a lapsed period, the investigator must
cease all research, and must submit a request to the IRB to continue research interventions or interactions for
some or all subjects when it is in the best interest of the subjects to continue. An investigator must clearly
distinguish and explain what research activities from which he or she will refrain as part of the lapse and what
2
Issued: 9/24/09
Effective: 9/24/09
Form #: 704
Last Reviewed: 9/24/09
Last Revised: 9/24/09
*Forms are subject to change. Check for the latest forms on the Tulane IRB web site.
Reporting Guidelines
research activities require continuation. The investigator must also explain the underlying reasons for which
the protocol exception is requested for each activity and each subject where an over-riding safety concern or
ethical issue indicates that it is in the best interests of the individual to continue participating.
Safety Reports/External Adverse Events (sponsor)
Safety Report (SR) alerts are issued by the FDA or the study sponsor to inform all researchers using the
same pharmacological compound about serious adverse events or reactions that have occurred in
patients/subjects. These events, considered external adverse events, may occur on the same clinical
investigation being conducted by a Tulane University investigator, or more often these SR events occur on
different clinical investigation using the same pharmacological compound as the Tulane University
investigator.
It is the Tulane University Investigator’s responsibility to ensure that each external adverse event is
reviewed to determine whether the event is reportable to the IRB. External adverse events should be
submitted to the IRB within the 10 working day timeframe if in the opinion of the Tulane University
researcher the event/s are Reportable Events or Problems.
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Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are
described in the IRB-approved documents; 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 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.
OR the event:
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changes the study’s risk/benefit profile; and/or
necessitates submission of a request to revise the IRB-approved consent document(s) and/or the
IRB-approved protocol.
Safety Reports that do not meet the 10 working day reporting timeframe are NOT reportable to the
IRB. The researcher should initial and date the Safety Report and file with research documentation.
Reporting Methods and Timeframes
The following are types of unanticipated problems/events required to report to the IRB. If the
unanticipated problem/event does not fit the categories, the event is NOT reportable to the IRB; however
may be reportable to the sponsor. Please notify the IRB within the specified reporting timeframe, followed
by follow-up reports, as required.
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Type of Event/Problem
Internal, unanticipated & serious problem/event;
Protocol violation (Major);
Change to the protocol without prior IRB approval to
Reporting Timeframe
3
Issued: 9/24/09
Effective: 9/24/09
Form #: 704
Last Reviewed: 9/24/09
Last Revised: 9/24/09
Reporting Guidelines
*Forms are subject to change. Check for the latest forms on the Tulane IRB web site.
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eliminate an apparent immediate hazard to a research
subject.
other event/problem involving subjects or others that is
unexpected, related or possibly related to the research, and
caused harm to others or places others at a greater risk of
harm as a result of the research.
5 working days
Protocol violation (Minor);
Any other unanticipated problem/event that in the opinion
of the investigator, involve risk to the subject, affect others
10 working days
in the research study, or significantly impact the integrity of
research data. For example: report occurrences of breaches
of confidentiality, accidental destruction of study records, or
unaccounted-for study drug.
Any external adverse effect/event described in the list of
Reportable Events/ Problems (e.g., Safety Report)
(1) Any Major Protocol Violation;
(2) Any Minor Protocol Violation
Any internal, unrelated death as determined by Tulane University
Investigator
[REQUIRED FOR CLINICAL INVESTIGATIONS ONLY]
10 working days, if event
constitutes an unanticipated
reportable event
(1) 5 working days
(2) 10 working days
Within 10 working days or at time
of Continuing Review, if not
previously reported
Important Notes when submitting reports to Tulane University IRB:
1. In order to maintain the subject's privacy, please do not include any names and/or other
personal identifiers in the report and remember to remove all identifiable, private information
from any supporting documentation you provide the IRB.
2. If the event/problem requires submission of a revision to previously approved documents, please
remember to submit a highlighted or underlined version of the revised document(s).
3. If an internal event/problem is unresolved at the time of initial reporting, a follow-up report is
required to be submitted if the AE is not resolved as expected or if the AE results in a chronic
condition or death.
Reporting DSMB Interim Reports to the IRB
The Principal Investigator (Lead Researcher) is expected to review any Data and Safety Monitoring interim
report and determine whether the report indicates a change in the risk/benefit profile. If the report
indicates a change in the risk/benefit profile, a report should be submitted to the IRB. If there is no change
in the risk/benefit profile, the DSMB report should be submitted at the time of continuing review.
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Issued: 9/24/09
Effective: 9/24/09
Form #: 704
Last Reviewed: 9/24/09
Last Revised: 9/24/09
*Forms are subject to change. Check for the latest forms on the Tulane IRB web site.
Reporting Guidelines
IRB Actions Regarding Unanticipated Problems Involving Risk to Participants or Others
The IRB will review the Unanticipated Problem/Event report in a timely manner and determine whether
the reported event constitutes a risk to participants or others. The IRB will consider a range of possible
actions:
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Suspend or terminate the research
Require investigator/s notify current participants when such information might be related to their
willingness to continue to take part in the research (e.g., re-consenting participants)
Request that the investigator place an “Administrative Hold” on the research activities pending
receipt of further information
Require modifications to the protocol and/or consent documents
Provide additional information to past participants (e.g., long-term risks have been identified that
could affect them)
Increase the frequency of continuing review
Impose additional monitoring requirements
Require additional training of the researcher and research team
Notify other Tulane University committees or departments; or other collaborating organizations
and facilities.
The IRB will report any unanticipated problems involving risk to participants or others to the Principal
Investigator, appropriate Tulane University officials, the funding agency or study sponsor, if applicable, the
Office for Human Research Protections and/or FDA, and any other applicable regulatory authorities.
IRB Authority to Suspend or Terminate Approval
The IRB also has the authority to suspend or terminate approval of research that has been associated with
unexpected serious harm to participants. When an IRB Committee takes such action, it is required to
provide a statement of reason for the action and to promptly report this action to the Principal Investigator,
Department Chair or School Dean, and other applicable Tulane University officials, the funding agency or
study sponsor, if applicable, the Office of Human Research Protections and/or FDA, and possibly other
regulatory authorities.
Serious Adverse Event Reporting Requirements for Human Gene Transfer Research
Principal Investigator (Lead Researcher) of human gene transfer (a.k.a. "gene therapy") protocols have
extra adverse event reporting responsibilities. In addition to submitting Unanticipated Problem reports to
the Tulane University IRB, they also must complete and submit to the NIH Office of Biotechnology
Activities' (OBA) Serious Adverse Event report form when a subject on a gene transfer protocol
experiences a hospitalization or a death. If the gene transfer study is supported by an external sponsor, this
reporting should be coordinated with the sponsor.
Failure to report gene transfer SAEs to the federal oversight bodies (FDA, NIH-OBA) may result in sanctions
for the individual researcher and for the institution. For more information regarding the additional AE
reporting responsibilities for human gene transfer research, please contact Tulane University Biomedical
IRB.
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Issued: 9/24/09
Effective: 9/24/09
Form #: 704
Last Reviewed: 9/24/09
Last Revised: 9/24/09
*Forms are subject to change. Check for the latest forms on the Tulane IRB web site.
Reporting Guidelines
Serious Adverse Events or Unanticipated Problems Involving Risk to Participants or Others Related
to a Humanitarian Use Device (HUD)
Whenever the physician or health care provider receives or otherwise becomes aware of information, from
any source, that reasonably suggests that a HUD has or may have caused or contributed to the death or
serious injury of a patient, the physician or health care provider must report such findings to the FDA and
the IRB as soon as possible, but no later than 5 days after the physician first learns of the event/problem.
This reporting is in addition to, not a substitute for, FDA and/or manufacturer reporting requirements in
accordance with 21 CFR 803.30.
The physician or health care provider must promptly report any FDA action regarding the death or serious
injury to the subject/patient, and to the Tulane University IRB.
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Issued: 9/24/09
Effective: 9/24/09
Form #: 704
Last Reviewed: 9/24/09
Last Revised: 9/24/09