Common Audit
Findings
UTHSC Institutional Review Board (IRB)
Authority to Audit
45 CFR 46.109(e)
An IRB shall conduct continuing review of research covered by
this policy at intervals appropriate to the degree of risk, but not
less than once per year, and shall have authority to observe or
have a third party observe the consent process and the
research.
21 CFR 56.109(f) gives the IRB the authority to observe, or have a
third party observe, the consent process and the research. When
and if the IRB is concerned about the conduct of the study or the
process for obtaining consent, the IRB may consider whether, as
part of providing adequate oversight of the study, an active audit is
warranted.
UTHSC IRB Policy
• The UTHSC IRB will have the authority or may designate a third
party to observe the conduct of any research activity, and may
review at any time all research records, including but not limited to
informed consent documents, regulatory files, IRB files, subjects’
research and medical records, clinical materials, storage and
distribution of investigational devices (e.g., drugs, devices, or
biologics), record storage, computer files, and results of
procedures and tests performed during the course of the research.
• Research compliance auditing staff will also have the authority to
observe the informed consent process and to interview subjects
either during or after their participation in research activities.
General Goals of Audits
• Assure protections for human subjects are implemented
• Verify that protections for human subjects are properly
documented
• Assess compliance with applicable regulations, guidance, and
local policies
• Enable investigator to avoid sanctions for non-compliance
• Assure that the University and affiliated institutions remain in
good standing with federal agencies that have oversight of human
subjects research activities
• Confirm that study data are accurate and reliable
How are we doing?
Audit program 2014-2015
• 58% of audited studies exhibited noncompliance in at least one area:
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28% Consent Process
26% Accuracy and Completeness of Study Records
25% Adherence with Continuation & Revision Policies
19% Inclusion/Exclusion Criteria
11% Protocol Adherence
9% Enrollment Numbers
6% Data Confidentiality
Correcting Problems:
General Considerations
Start every study with a delegation of responsibilities log and
review it with all study team members. Make sure your
delegation log matches your IRB study application under Section
(415).
Our Tools & Guides page includes a Delegation of Responsibilities
template:
http://www.uthsc.edu/research/research_compliance/IRB/guides.
php
Correcting Problems:
General Considerations
Know the local policy and guidelines.
Visit our SOP page:
http://uthsc.edu/research/research_compl
iance/IRB/policies.php
Read the document, “Things to
Remember When Conducting
Research,” and use the Project
Checklists found here:
http://www.uthsc.edu/research/resear
ch_compliance/IRB/guides.php
Call the IRB office when you are unsure!
Documenting is the KEY…
Consent Process Problems
• Enrolled subjects were consented by people not listed as key study
personnel or as having the responsibility for obtaining informed
consent.
• Verification of the informed consent interview was not present in the
research record.
• Unapproved/unstamped consent forms were used to consent
subjects.
• Child assent was not obtained on a regular basis and/or no reason
was documented for not obtaining assent.
• Original, signed consent forms were missing.
Consent Process Problems
• Non-English speaking subjects were enrolled using an English
version of the consent form.
• Adult subjects were enrolled using the LAR’s permission with no
documentation about the inability of the subject to give consent.
• Date and/or time of the consent was not recorded in the document.
• Permission from the LAR was obtained over the phone. (Consenting
over the phone constitutes an alteration of the consent process that
must be approved by the IRB and must be requested in the
application.)
How do we correct them?
•
Include a note regarding the consent process ‐ how it was conducted;
whether questions were asked/answered; the fact that a signed copy
was given to the subject; whether a translator was present (if applicable)
Template is available at
http://uthsc.edu/research/research_compliance/IRB/guides.php
•
Before starting consent process, check to make sure you have latest
approved version from IRB. Tip: get the last stamped-approved version
directly from iMedRIS each time.
•
An investigator must sign the consent form within 72 hours after the
subject and person obtaining consent.
•
You must keep the original, signed consent form in the study files.
Problems With Study Records
There was no documentation or incomplete documentation regarding:
• Site study visits
• Phone call visits
• Treatment and doses (including drug dispensing)
• Date and time for lab tests
• Questionnaires - no record for some subjects
The only research record was the CONSENT FORM…yikes!
How do we correct them?
Read the protocol and IRB study application carefully before starting
the study, AND:
• Make sure you capture necessary study data.
• Use the approved data collection tools.
• Set up a regular research team meeting time to review study data.
Document, document, document
(if it isn’t written, it didn’t happen)
Continuation & Revision
Problems
• Accrual of subjects was continued
after IRB approval lapses.
• Changes were made in study
interventions, assessment tools,
visits, etc. without IRB approval.
How do we correct them?
• If you let IRB approval for your study expire, you:
 Must cease all study activities on the expiration date
 May not enroll any new subjects
 May not obtain any data on current subjects until your study
has been approved (again) by the IRB to continue for another
year
 May possibly be required to submit a new application again
 Caveat: if stopping activities could pose any harm to the
subject, make a written request to the IRB for each subject to
continue study interventions
• Any and all changes you wish to make to your project must be
submitted to the IRB (via a Form 2) and approved before
implementation.
Problems with
Inclusion/Exclusion Criteria
• Subjects did not meet the inclusion/exclusion criteria for
the study.
• No source documentation confirming eligibility criteria
was recorded.
How do we correct them?
• You and your team READ the protocol and KNOW the eligibility criteria.
• Use an eligibility checklist. A template is available at:
http://uthsc.edu/research/research_compliance/IRB/guides.php
• In case of intentional deviation from approved eligibility criteria:
When a local investigator receives a protocol waiver from a study
sponsor, or the principal investigator of an investigator-initiated
study proposes to enroll a subject who does not meet the approved
inclusion/exclusion criteria, the details of the proposed waiver,
subject identification, and all supporting documentation must be
submitted to the UTHSC IRB for review and approval prior to
implementation. The IRB will acknowledge receipt of such waiver
requests.
Protocol Adherence Problems
• More information/data was recorded than
described in the application/protocol/consent
form.
• The follow-up visit notes were missing; a visit
was scheduled outside of the protocol
window; or some tests were not completed
(i.e., no documentation exists).
How do we correct them?
Be sure to use only approved data collection tools that match your IRBapproved protocol, study application, and consent form.
How do we correct them?
• Follow the local policy:
• The principal investigator is responsible for reporting all Major
Protocol Deviations occurring at the local research site to the IRB.
• A Major Deviation:
 Has harmed or posed a significant risk of substantive harm to the
subject;
 Has compromised the scientific integrity of the data collected;
 Appears to result from willing/knowing misconduct on the part of
an investigator/staff; or
 Appears to involve some other serious or continuing
noncompliance with federal, state, or local research regulations.
How do we correct them?
• All major deviations should be reported as soon as possible,
but no later than 5 working days after the
investigator/coordinator becomes aware of the event.
• Minor deviations do not have to be reported to the IRB;
however, a note-to-file should be made in the research
record indicating:
 What the minor deviation was;
 The reason it occurred; and
 The communication that took place or plan implemented
so that the deviation would not occur again
• Remember that the continued occurrence of minor
deviations could compromise the scientific integrity of the
research data collected
Enrollment Number Problems
• More subjects were enrolled than approved by the IRB
Enrollment occurs when the consent
form is signed, not when the subject
is randomized. Therefore, an
estimate of screened failures should
be incorporated into the target
enrollment number submitted to the
IRB. Also, the number of subjects
who signed the consent form, not just
the number of subjects who were
randomized, should be included on
the renewal application under the
number of subjects accrued.
How do we correct them?
• Check your IRB-approved study application, under section 1400,
and know how many subjects you are approved to enroll.
• Keep a consent log. A template is available at:
http://uthsc.edu/research/research_compliance/IRB/guides.php
• If you need more subjects, submit a Form 2: Change Request &
Amendments for IRB review and approval before enrolling additional
subjects.
Investigator Noncompliance
The IRB recognizes that non-compliance with approved protocols
may occur. It is the responsibility of the Principal Investigator to
notify the IRB regarding major protocol deviations or to call the IRB
when you are unsure of whether you must report an incident.
The IRB has the authority to place
research activities on hold, as well
as to suspend or terminate approval
of research that is not being
conducted in accordance with the
IRB policies or federal regulations
for the protection of human
subjects.
Summary of Best Practices
 Perform all and only those research procedures that are
specifically described in your IRB-approved
application/protocol
 Use compliance tools & checklists available on the IRB website
 Use the consent form & research record to carefully document
all aspects of the informed consent process
 Submit continuation applications 3 weeks before your
expiration date
 Secure approval for all study revisions prior to implementation