INDIANA UNIVERSITY HEALTH
BLOOMINGTON
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
APPROVED: Wanda Katinszky
ORIGINATION: 09/26/2003
IRB – INSTITUTIONAL REVIEW BOARD
POLICY NUMBER: RR 402
PAGE 1 OF 16
REVIEW WITH REVISION: 08/05/2013
REVIEW ONLY:
1. POLICY
No investigator has a right to conduct research within this institution. Rather, it is a
privilege granted by society as a whole and the Trustees of IU Health Bloomington in
particular. IRB approval may be withdrawn at any time if warranted by the conduct of the
research. The regulations authorize the IRB to establish procedures for the ongoing
monitoring of research activities involving human subjects. Periodic and ongoing review
of research activities is necessary as a means of ensuring the relationship of the risks
and benefits to subjects participating in research studies remain acceptable throughout
the conduct of the study and that the consent document contains the information
necessary for subjects to make an informed decision about their participation or
continuation in the study. IRB approval may be withdrawn if the risks to the subjects are
determined to be unreasonably high or there is evidence that the investigator is not
conducting the investigation in compliance with federal, and state regulations, IRB
requirements or Institutional policies. Such findings may result in more frequent review of
the study to determine if approval should be withdrawn or enrollment stopped until
corrective measures can be taken or the study terminated.
Changes to Previously Approved Research & Prompt Reporting include, but may not be
limited to, the following events:
 Amendment
 Changes made to approved research without IRB approval
 Review of serious and unexpected adverse events
 Noncompliance
 Internal change to the IRB approved protocol taken without IRB review
 Major protocol deviations
 Review of significant new findings that indicates an unexpected change to the risks or
potential benefits of the research, in terms of severity or frequency
 Reports from employees or staff
 Complaints of a participant that cannot be resolved by the research team
 Any change in FDA labeling or withdrawal from marketing of a drug, device or biologic
used in research
 An unanticipated adverse device effect
 Investigator or sponsor-initiated study suspension or hold
Federal Regulations [45CFR46.103(b)(5) and 21CFR56.108(b)] require the IRB to ensure
that investigators promptly report “any unanticipated problems involving risk to subjects or
others”, any serious or continuing noncompliance with the federal regulations or the
requirements or determinations of the IRB, and any suspension or termination of IRB
approval. In keeping with this requirement, investigators are required to promptly report to
the IRB unanticipated problems, serious or continuing noncompliance, and suspensions or
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 2 OF 16
terminations. In accordance with the Federal regulations, the IU Health Bloomington IRB has
established the following policies and procedures for the reporting of these events.
Specific Policies
1.1 Changes to Previously Approved Research & Prompt Reporting
Changes in approved research, during the period for which approval has already be
given, may not be initiated without prior IRB review (full or expedited review, as
appropriate) and approval, except where necessary to eliminate apparent immediate
hazards to human subjects. In this situation, the changes must be promptly reported to
the IRB on the Prompt Reporting form. Otherwise, the request for a change to the
approved research must be submitted to the IRB on the Amendment form.
1.1.1 Investigators or Sponsors must submit requests for changes to the IRB by the
completion and submission of an Amendment Form. Upon receipt of the
protocol change, the Chair, IRB Administrator or designee will determine if the
revision meets the criteria for minimal risk. If the change represents more than
a minimal risk to subjects, it must be reviewed and approved by the convened
board. Minor changes, involving no more than minimal risk to the subject will be
reviewed by the expedited review procedure.
1.1.2 Amendments to Expedited Research. Modifications to research previously
approved under expedited procedures shall be reviewed under expedited
procedures as long as the changes requested continue to meet the expedited
category(ies) and do not substantially increase the risk to participants.
1.1.3 Amendments to Research Previously Approved by the convened IRB. Pursuant
to 45 CFR 46.110(b)(2), minor changes to research previously approved by the
convened IRB may be reviewed and approved under an expedited review
procedure; a Minor Amendment. Examples include, but are not limited to,
change in study title, extension of recruitment period, decrease in amount of
blood drawn, etc. Substantive changes and changes that involve increased risks
or discomforts must be reviewed and approved by the convened IRB; a Major
Amendment. New primary objectives or significant changes in the statistical
design of the research do not constitute a new study and are not justified as
amendments.
1.2
Serious and Unexpected Adverse Events
HHS regulations (45 CFR 46) do not define or use the term “adverse event”, nor is there
a common definition of this term across government and non-government entities.
However, the regulations do address the need to report “unanticipated problems.” Only
a small subset of adverse events occurring in human subjects participating in research
will meet the definition of an unanticipated problem. Because the federal regulations
require that the IRB has written procedures for ensuring prompt reporting to the IRB,
appropriate institutional officials, and any supporting department or agency head of any
unanticipated problems, and not adverse events, not all adverse events will require
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 3 OF 16
prompt reporting. In fact, the vast majority of adverse events occurring in human
subjects are not unanticipated problems. Only if the adverse event meets the three
criteria of an unanticipated problem does it require reporting :
 unexpected,
 related or possibly related to participation, and
 suggests that the research places subjects or others at a greater risk of harm
than was previously known or recognized) and requires changes to the research
protocol or informed consent process/document or other corrective actions in
order to protect the safety, welfare, or rights of subjects or others.
Diagram taken from OHRP Guidance on Unanticipated Problems and Adverse Events
(January 15, 2007).
The following Venn diagram summarizes the general relationship between adverse
events and unanticipated problems (OHRP Guidance on Unanticipated Problems and
Adverse Events [January 15, 2007]). :
The diagram illustrates three key points:
1. The vast majority of adverse events occurring in human subjects are not
unanticipated problems (Area A).
2. A small portion of adverse events are unanticipated problems (Area B).
3. Unanticipated problems include other incidents, experiences, and outcomes that are
not adverse events (Area C).
1.2.1 Assessing whether an adverse event is unexpected.
Adverse Events: Any untoward or unfavorable medical occurrence in a human
subject, including any abnormal sign (e.g. abnormal physical exam or laboratory
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 4 OF 16
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 events encompass both physical and
psychological harms.
Consider that the vast majority of adverse events occurring in the context of
research are expected in light of 1) the known toxicities and side effects of the
research procedures; 2) the expected natural progression of subjects’ underlying
diseases, disorders, and conditions; and 3) subjects’ predisposing risk factor
profiles for the adverse event. Thus, most individual adverse events do not meet
the first criterion for an unanticipated problem and do not require prompt
reporting to the IRB.
1.2.2 Assessing whether an adverse event is related or possibly related to
participation.
Related or Possibly Related to Participation in Research: There is a reasonable
possibility that the incident, experience, or outcome may have been caused by
the procedures involved in the research.
In general, adverse events that are determined to be at least partially caused by
the procedures involved in the research would be considered related to
participation in the research, whereas adverse events determined to be solely
caused by an underlying disease, disorder, or condition of the subjects or other
circumstances unrelated to either the research or any underlying disease,
disorder, or condition of the subject would be considered unrelated to
participation in the research. Many individual adverse events occurring in the
context of research are not related to participation in the research and,
therefore, do not meet the second criterion for an unanticipated problem and do
not require prompt reporting to the IRB’s.
1.2.3 Assessing whether an adverse event suggests that the research places subjects
or others at a greater risk of harm than was previously known or recognized. The
first step in assessing whether an adverse event meets the third criterion for an
unanticipated problem is to determine whether the adverse event is serious.
A Serious Adverse Event is any adverse event that results in death; is lifethreatening (places the subject at immediate risk of death from the event as it
occurred) results in inpatient hospitalization or prolongation of existing
hospitalization; results in a persistent or significant disability/incapacity; results
in a congenital anomaly/birth defect; or based upon appropriate medical
judgment, may jeopardize the subject’s health and may require medical or
surgical intervention to prevent one of the other outcomes listed in this
definition.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 5 OF 16
Adverse events that are unexpected, related or possibly related to participation
in research, and serious are considered to be the most important subset of
adverse events representing unanticipated problems because such events
suggest that the research places subjects or others at a greater risk of physical
or psychological harm than was previously known or recognized and routinely
warrant consideration of substantive changes in the research protocol or
informed consent process/document or other corrective actions in order to
protect the safety, welfare, or rights of subjects. However, other adverse events
that are unexpected and related or possibly related to participation in the
research, but not serious, would also be unanticipated problems if they suggest
that the research places subjects or others at a greater risk of physical or
psychological harm than was previously known or recognized.
1.2.4 Reporting Internal Adverse Events to the IRB
For an internal adverse event, a local investigator typically becomes aware of the
event directly from the subject, another collaborating local investigator, or the
subject’s healthcare provider. Upon becoming aware of an internal adverse
event, the investigator should assess whether the adverse event represents an
unanticipated problem following the guidelines described above. If the
investigator determines that the adverse event does in fact represent an
unanticipated problem and requires changes to the research protocol or
informed consent process/document or other corrective actions in order to
protect the safety, welfare, or rights of subjects or others, the investigator must
report it to the IRB within five business days of the investigator becoming aware
of the event.
Reporting Time Frame: All internal serious adverse events must be reported to
the IRB within five (5) business days of the investigator becoming aware of the
event.
1.2.5
Reporting External Adverse Events to the IRB
The majority of adverse event reports received by investigators are reports of
external adverse events experienced by subjects enrolled in multicenter clinical
trials. Reports of individual external adverse events often lack sufficient
information to allow the investigators or IRB at each institution engaged in a
multicenter clinical trial to make meaningful judgments about whether the
adverse events are unanticipated problems. As such, external adverse events
should only be reported to the IRB when a determination has been made that
the events meet the criteria for an unanticipated problem and requires changes
to the research protocol or informed consent process/document or other
corrective actions in order to protect the safety, welfare, or rights of subjects or
others. Individual external adverse events are expected to rarely meet these
criteria. Note that, in general, investigators and the IRB are not appropriately
situated to assess the significance of individual external adverse events. These
adverse events are better submitted for review and analysis to a monitoring
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 6 OF 16
entity (e.g. research sponsor, DSMB/DMC) in accordance with the monitoring
plan described in the IRB-approved protocol. When an investigator receives a
report of an external adverse event, he/she should review the report and assess
whether it satisfies the criteria of an unanticipated problem.
If the external adverse event is determined to represent an unanticipated
problem and requires changes to the research protocol or informed consent
process/document or other corrective actions in order to protect the safety,
welfare, or rights or subjects or others, the investigator must report it to the IRB
within five business days of the investigator becoming aware of the event.
Reporting Time Frame: Five (5) business days from notification of the event.
1.3
Reporting Other Unanticipated Problems (not related to adverse events) to the IRB
There are other types of events that meet the IRB’s definition of unanticipated problems
involving risk to subjects or others. Examples of these types of unanticipated problems
are listed in section 1 of this policy.
If an event is determined to represent an unanticipated problem and requires changes
to the research protocol or informed consent process/document or other corrective
actions in order to protect the safety, welfare, or rights of subjects of others, the
investigator must report it to the IRB using the Prompt Reporting Form within five (5)
business days of the investigator becoming aware of the event. If determined not be an
unanticipated problem, the report will be reviewed at a convened IRB meeting for
possible action.
Reports of unanticipated problems can come from a number of different sources,
including investigators, members of the research team, study sponsor, regulatory body
(e.g. OHRP, FDA), subjects and/or their families, institutional personnel or committees,
the media, the public, or anonymous sources. Additionally, the IRB can identify
unanticipated problems and noncompliance during its review of research studies.
Reporting Time Frame: Five (5) business days from notification of the event.
1.4
Reporting Noncompliance to the IRB
As part of its oversight responsibilities the IRB must establish procedures for the
evaluation of noncompliance and the prompt reporting of serious or continuing
noncompliance with the federal and institutional policies. All noncompliance must be
reported to the IRB.
Definitions
Noncompliance: Any instance of an investigator failing to comply with relevant Federal,
State, or local laws or regulations, the Good Clinical Practice Act, IU Health Bloomington
IRB policies and procedures, or determinations of the IU Health Bloomington IRB that
has been communicated to the investigator in writing. The board should consider any
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 7 OF 16
extenuating circumstances when making a determination about whether
noncompliance is continuing or serious.
Continuing Noncompliance: An instance of noncompliance that involves either 1) the
investigator failing to respond to the IRB’s written ‘notification of noncompliance’ by the
specified deadline, or 2) the investigator repeating the same type of noncompliance
behavior in the same or different studies (e.g., two instances of failure to submit a
continuing review report on time).
Serious Noncompliance: An instance of noncompliance that represents a significant
threat to the rights, safety, or welfare of research participants or that is defined as
‘serious’ by any federal agency regarding the conduct of clinical trials. Examples of
serious of noncompliance may include: current IRB-approved consent form not signed
and dated by the subject (or the subject’s legally authorized representative) before
beginning any study-related procedures; performance of any study activities (except
those necessary to protect the rights, safety and welfare of participants) without IRB
approval, any instance of fraud, falsification of information, or forgery, etc.
Noncompliance: Non-Serious and Non-Continuing: Isolated, unintentional deviations
from the approved research protocol and unapproved changes to research practices
that do not increase risk to subjects. This may include but are not limited to: revising
the advertisement used to recruit subjects without prior IU Health Bloomington IRB
approval; failure to notify the IU Health Bloomington IRB before an investigator is added
to, or removed from, an ongoing study; and minor, non-substantive, changes in wording
of a consent form.
Noncompliance: Serious and/or Continuing: Practices that appear to: 1) cause injury
(physical, psychological, emotional, etc.) or any other unanticipated problems involving
risks to subjects and/or others, or 2) constitute serious or repeated noncompliance with
relevant Federal, State, or local regulations, the Good Clinical Practice Act, IU Health
Bloomington IRB policies and procedures, or determinations of the IU Health
Bloomington IRB. Repeated non-compliance that, in the opinion of the IU Health
Bloomington IRB, Chair, Co-Chair or designee, suggests the likelihood that noncompliance will continue without intervention. This may include, but is not limited to:
failure to obtain IU Health Bloomington IRB approval for research involving human
subjects; inadequate or non-existent procedures for informed consent; inadequate
supervision in research involving drugs, devices or procedures; failure to follow
recommendations made by the IU Health Bloomington IRB to insure the safety of
subjects; failure to report adverse events or proposed changes to the IU Health
Bloomington IRB; and failure to provide ongoing progress reports or timely renewal of
the protocol.
Reporting Time Frame: Five (5) business days from knowledge of observed or apparent
noncompliance.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 8 OF 16
1.4.1 Report of Observed or Apparent Noncompliance
1.4.1.1 Reports of observed or apparent noncompliance are to be reported to
the IRB using the Noncompliance Reporting Form within five (5)
business days of knowledge of the noncompliance.
1.4.1.2 Upon receipt of the report, the IRB Director, or designee, will determine
whether the report represents noncompliance. If not, the IRB Director,
or designee, will sign the report and return it to the investigator and
retain a copy in the study file. No further action will be required.
1.4.1.3 If the IRB Director, or designee, determines that the report represents
noncompliance, he/she may/may not consult with the IRB Chair, or
designee, to determine whether the report represents serious or
continuing noncompliance. If it is determined that the noncompliance is
not serious nor continuing, the IRB Director, or designee, and/or IRB
Chair, or designee, will work with the investigator to create a corrective
action plan. If the investigator fails to respond or a reasonable
negotiation cannot be accomplished, the noncompliance is handled as
continuing noncompliance and will be reviewed at a convened IRB
meeting.
1.4.1.4 If it is determined by the IRB Director, IRB Chair or designee determine
that the report likely represents serious or continuing noncompliance,
the matter will be referred to the convened IRB for review. Only the
convened IRB can make a determination of serious or continuing
noncompliance.
1.4.1.5 The IRB Director, IRB Chair or designee, or convened IRB has the
right to request additional information and/or require a specific action
as a result of the noncompliance report.
Reporting Time Frame: Five (5) business days from knowledge of observed or
apparent noncompliance.
1.4.2 Reporting Allegations of Noncompliance to the IRB
1.4.2.1 Allegations of noncompliance may be received by the IRB at any time
and from a number of sources including, but not limited to, a member
of the research team, a study participant, a third party, etc.
1.4.2.2 The IRB Director, or designee, will gather information regarding the
allegation, conduct an investigation, if necessary, and determine
whether the allegation is true.
1.4.2.3 If the IRB Director, or designee, is unable to make a determination,
he/she will involve the IRB Chair to make the determination.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 9 OF 16
1.4.2.4 If the IRB Director, IRB Chair or designee finds the allegation to be false,
the findings will be documented, filed and communicated to the
complainant, respondent, and investigator, as appropriate.
1.4.2.5 If the IRB Director, IRB Chair or designee finds the allegation to be true
and potentially serious and/or continuing it will be handled as described
below.
1.4.2.6 If the IRB Director, IRB Chair or designee cannot determine whether the
allegation of noncompliance is true, the matter will be referred to the
convened board for review and determination.
1.4.2.7 The IRB Director, IRB Chair or designee or the convened board have the
right to request additional information or require suspension of IRB
approval as a result of the noncompliance allegation.
1.4.2.8 If at any point during the investigation it is believed the allegations
raises legal issues, the hospital attorney will be contacted.
1.5 IRB Responsibilities When Reviewing Unanticipated Problems and Noncompliance
Reports
1.5.1 When the IRB receives a report of an unanticipated problem or noncompliance,
it must review the report to determine whether the affected research protocol
still satisfies the requirements for IRB approval under 45 CFR 46.111.
Specifically, the IRB shall consider whether risks to subjects are minimized and
reasonable compared to the benefits.
1.5.2 Pursuant to 45 CFR 46.109(a), the IRB has the authority to require, as a
condition of continued approval, submission of more detailed information by the
investigator(s), sponsor, study coordinating center or DSMB/DMC about any
unanticipated problem or noncompliance.
1.5.3 If it is determined that a report does represent an unanticipated problem or
serious or continuing noncompliance, the IRB must report it to the appropriate
institutional officials, regulatory agencies (e.g. OHRP, FDA), and others, as
application. If it is determined that the report does not represent an
unanticipated problem or serious or continuing noncompliance, no further action
is required.
1.5.4 Upon review of a report of an unanticipated problem or noncompliance, the IRB
will determine if any action must be taken. The IRB will consider the rights and
welfare of the participants when taking any action of imposing a sanction.
Possible actions or sanctions include, but are not limited to:
1.5.4.1 No action; the protocol continues as previously approved.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 10 OF 16
1.5.4.2
Proposed corrective action plan is adequate and no further action is
necessary.
1.5.4.3
Refer to or counsel with other institutional entities.
1.5.4.4
Restrict use of or destroy research data collected.
1.5.4.5
Audit the research.
1.5.4.6
Modify the research protocol and/or informed consent/process.
1.5.4.7
Notify or reconsent past and/or current participants if the report may
relate to their willingness to continue to take part in the study.
1.5.4.8
Withdraw currently enrolled participants if it is thought to be in their
best interest.
1.5.4.9
Require additional training of the investigator and/or research team.
1.5.4.10 Modify the continuing review schedule.
1.5.4.11 Require increased reporting by the investigator and/or increased
monitoring of the research and/or informed consent process.
1.5.4.12 Restrict privileges of investigator to conduct human research.
1.5.4.13 Suspend or terminate research or suspend specific research activities
(e.g. recruitment, enrollment, interaction/invention, and/or follow-up).
1.5.4.14 Other actions deemed appropriate.
1.6 IRB Imposed Suspension and Termination Due to Unanticipated Problems and Serious
or Continuing Noncompliance
1.6.1 Pursuant to 45 CFR 46.113, the IRB has the authority to suspend or terminate
approval of research that is not being conducted according to the IRB’s
requirements, institutional policies, federal or state regulations, or has been
associated with unexpected serious harm to subjects. Any suspension or
termination of approval shall include a statement of the reasons for the IRB’s
action and shall be reported promptly to the investigator, appropriate
institutional officials, the department or agency head, OHRP, FDA and any local
agencies as required by legislation.
1.6.2 Suspensions and terminations cannot be overturned by Institutional Officials.
1.6.3 Suspension of research is typically made at a convened IRB meeting. However,
the decision can be made on an urgent basis by the Chair. If the Chair suspends
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 11 OF 16
a study, it must be reported to the full board for consideration and possible
action. Termination of research can only be made by the convened IRB.
1.6.4 Any unanticipated problems or outcomes resulting from the suspension or
termination must be reported to the IRB.
1.6.5 When the IRB suspends or terminates a research study, they will also consider
whether this suspension or termination requires subjects be withdrawn from the
study and/or places them in harm.
1.6.6 When subjects must be withdrawn from a study, the IRB will consider the safety,
rights and welfare of subjects and determine necessary termination procedures
(e.g. drug tapering, final visit, lab tests, other follow-up, and/or arrangements for
continued care).
1.6.7 If the IRB determines that the suspension or termination does place the subjects
at harm and/or follow-up of subjects for safety reasons is permitted or required,
the IRB will determine which subjects are to be notified, e.g. current or past
participants, and the manner in which they are to be notified, e.g. in writing or by
telephone. Depending upon the reasons for the suspension or termination and
the design of the study, the RIB may require that any of the following individuals
be notified of the suspension or termination:
1.6.7.1 All subject who have been or are currently enrolled;
1.6.7.2
Only current enrolled and active subjects;
1.6.7.3
Only subjects who participated in a certain aspect of the study.
1.6.8 An investigator(s) may request to attend an IRB meeting to discuss a suspension
or termination in order to provide clarification of the issues. An investigator(s)
may request in writing that the IRB reconsider a suspension or termination,
within 10 days of such action.
2. SCOPE
These policies and procedures apply to all research submitted to the IRB.
3. RESPONSIBILITY
IRB Administrator designee is responsible for establishing the processes for conducting
ongoing reviews of research.
IRB Chairperson or designee is responsible for preliminary assessments of adverse events,
significant, noncompliance allegations, new findings and the need for third party verification.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 12 OF 16
4. APPLICABLE REGULATIONS AND GUIDELINES
21 CFR 812.64
21 CFR 56.108, 56.109, 56.113
45 CFR 46.103, 46.109, 46.113, 46.115
FDA Information Sheets, 1998
5. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
6. ATTACHMENTS
RR 402-A
RR 402-B
RR 402-C
RR 402-D
Amendment Form
Prompt Reporting Form
Noncompliance Reporting Form
Noncompliance/Complaint Investigation Form
7. PROCESS OVERVIEW
Describe the requirements for the continuing review that occurs after initial research
approval and prior to review for renewal of IRB approval.
8. PROCEDURES EMPLOYED TO IMPLEMENT THIS POLICY
A. Amendment
Who
IRB Administrator
Task
Tool
An amendment or change in the research may be Amendment Form
received via fax, mail/delivery, and internet or
during a site visit.
Upon receipt, stamp IU Health Bloomington IRB
Received on the report and input information in
the database.
Attach all information related to the amendment
to the study file.
IRB Chair, or
designee/
IRB Administrator
Review all amendments received. Triage to
determine those that can be reviewed expedited
versus those that will need to be placed on the
IRB Agenda and reviewed by the convened board.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 13 OF 16
B. Serious, Unexpected Adverse Events & Related/Possibly Related to Study
Who
IRB Chair/IRB
Administrator
Task
A report of an Adverse Event that requires
changes to the research protocol or informed
consent process/document or other corrective
actions in order to protect the safety, welfare, or
rights of subjects or others may be received via
fax, mail/delivery, phone, internet, during a site
visit.
Tool
Prompt Reporting
Form
Upon receipt, stamp IU Health Bloomington IRB
Received date on the front page of the report.
If notified by phone, complete the Prompt
Reporting form, record the information conveyed
and ask for additional information as indicated
on the form.
Input the adverse event onto the appropriate
database.
Attach all information related to the adverse
event to the report.
Provide a report to the convened board at the
next scheduled meeting.
IRB Administrator
IRB Chairperson, or
designee
Triage and forward the report on to the IRB
chairperson, or designee, for review.
Review AE/SAE reports. If the reviewer
Prompt Reporting
determines that action may be needed to protect Form
the safety of research subjects due to the nature
or frequency of reported adverse events, he/she
may take such action and/or the full IRB or
designated subcommittee will review the adverse
events and study in question to determine action,
if any, by the IRB.
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 14 OF 16
C. Reports of Noncompliance
Who
IRB Administrator
Task
Complaint or allegations of noncompliance
received by the IRB Office.
IRB
Director/designee/
Chair
Preliminary determination whether the affected
Noncompliance
protocol still satisfies the requirements for IRB
Investigation Form
approval. Additionally, a preliminary
determination will be made whether or not to
suspend the research; will be made within two
business days of the receipt of the allegation.
This decision is generally made by the IRB,
however, may be done by the Chair on an urgent
basis. If suspended by the Chair, the IRB must be
notified at the next convened meeting.
IRB
Director/designee/
IRB Chair
If it is found that the allegations are false, the
findings will be documented, filed and
communicated to the complainant, respondent
and investigator, as appropriate.
If it is found that the allegations are true and
potentially serious and/or continuing, the IRB
Director/designee/Chair will make the
determination whether the report represents
serious or continuing noncompliance. If unable
to make the determination the matter will go to
the IRB.
IRB Director/IRB
Chair/Designee
If determined to be a case of noncompliance, by
the IRB Director, designee and/or IRB Chair, that
represents serious or continuing noncompliance,
the matter will be referred to the convened IRB
for review who will make the determination of
serious or continuing noncompliance.
Tool
Noncompliance
Reporting Form
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 15 OF 16
The IRB Director/designee/IRB Chair will:
readdress the possible need for suspension of
the studies activities for the study in question
and possibly others; the investigation summary
will be placed on the agenda at the next
scheduled meeting of the IRB; a written report
summarizing the investigation findings will be
sent to the investigator involved in the allegation;
the investigator will be provided the opportunity
to discuss the investigation summary at the next
scheduled IRB meeting; and, once the IRB has
completed its investigation, a vote will be taken
to determine whether noncompliance of a
serious and/or continuing nature has occurred.
If noncompliance is found, the IRB will devise
and vote on a corrective action plan.
If noncompliance is found, the IRB will devise
and vote on a corrective action plan.
C. Major Protocol Deviation/Violations
Who
Task
IRB Administrator
A report of a major protocol deviation/violation
may be received via fax, mail/delivery, phone,
internet, or during a site visit.
Upon receipt, date-stamp the current date on the
report. If notified by phone, indicate receipt of
the phone call on the Prompt Reporting Form
Input the report into the appropriate database.
Attach all information to the appropriate study
file and provide to the IRB for review.
IRB Chair or
designee/IRB
Members
If the deviation or violation is deemed significant
by the Chairperson, designee, or IRB, possible
revisions or sanctions may be imposed as
outlined in this policy.
Tool
Prompt Reporting
Form
TITLE: Changes to Previously Approved
Research, Unanticipated Problems &
Noncompliance
REVIEW WITH REVISION: 08/05/2013
POLICY NUMBER: RR 402
PAGE 16 OF 16
D. Other Unanticipated Problems
Who
Task
IRB Administrator
An unanticipated problem or change in the
research may be received via fax, mail/delivery,
internet, or during a site visit.
Upon receipt, date-stamp the current date on the
report.
Input the information onto the appropriate
database.
Attach all information related to the
unanticipated problem to the study file for initial
review.
Review all reports received. Triage to determine
which can be reviewed by expedited review or will
need to be reviewed by the full board. Forward on
to Chair as applicable.
Tool
Prompt Reporting
Form