Current through all regulations passed and filed through September 16, 2024
(A)
Policy
statement
All clinical trials conducted at the
university of Toledo ("university") are subject to internal audit inspections,
including those trials sponsored by pharmaceutical and/or device companies,
national institute of health ("NIH"), other sponsors, and those that are
investigator-initiated. The jacobson center for clinical and translational
research ("JCCTR") is responsible for conducting and overseeing the internal
audit compliance program.
(B)
Purpose of
policy
The primary purpose of the internal
audit process is to ensure the protection of human subjects, verify the
validity and accuracy of data collection, identify noncompliance, and take
corrective action when necessary. The audit process involves verifying subject
eligibility, protocol adherence, and regulatory compliance according to federal
drug administration ("FDA"), international conference on harmonization ("ICH")
good clinical practice, university policies, and all other applicable
regulations. The internal auditing of clinical trials will promote continuous
improvement opportunities by providing an increased awareness of university
policies to researchers and staff as well as education of best practices to
ensure the university is conducting consistent high quality
research.
(C)
Scope
Internal audits will be categorized as:
targeted, for-cause, and informal audits that are performed to assist in
preparations for a scheduled or anticipated inspection by the FDA or sponsor.
Targeted audits are routine and selection is based on prioritized set criteria
(see (D)(1) of this rule) which includes those with an increased likelihood for
an external audit (e.g. high enrollment) or a specific category of research
such as gene transfer research. For-cause audits can be initiated at the
request of the institutional review board ("IRB"), research administration, or
some other group or person who has raised substantive concerns regarding study
conduct. Informal audits can be requested by the principal investigator ("PI")
or research staff and is dependent upon current work flows and resource
availability and schedules.
(D)
Targeted internal
audit procedures
(1)
The internal audit process begins with selecting a
study protocol to audit. Set criteria are used to prioritize all active
clinical research studies: new investigators and/or research coordinators,
number of subjects enrolled, sponsorship, disease site, and
complexity/high-risk studies.
(2)
The clinical
research auditor will coordinate all internal audits.
The PI and research staff will be sent
a notification letter via email that contains the following:
(a)
The study
title/protocol that will be audited.
(b)
The agreed dates
the auditor will be on site.
(c)
That all subject
records need to be up-to-date and available. The auditor will randomly select
which subjects will be audited during the visit.
(d)
A copy of the FDA
audit preparation guidance for clinical investigations checklist that
highlights what regulatory documents the auditor will be reviewing throughout
the internal investigation. The PI is responsible for ensuring that those
documents highlighted on the checklist are available during the departmental
inspection.
(3)
The clinical research auditor will coordinate a date
and time to meet with the investigational pharmacist (if applicable) to review
all study drug accountability and dispensing records.
(4)
The clinical
research auditor will complete an audit review form on every subject monitored
during the inspection. The following elements will be reviewed:
(a)
Informed consent
form ("ICF") and documentation of the consent process.
(b)
Subject
eligibility and screening compliance.
(c)
Protocol required
procedures/visits are complete.
(d)
Adverse and
serious adverse events have been properly reported to
sponsor/IRB.
(e)
Lab and diagnostic testing have been performed per
protocol requirements.
(f)
Data collection is attributable, legible,
contemporaneous, original and accurate (ALCOA standards for
GCP).
(5)
Exit interview: The PI and key study staff will attend
the exit interview or notify the clinical research auditor of the need to
reschedule the exit interview. Any rescheduled exit interview must occur
without delay. The clinical research auditor will present the findings from the
audit and respond to any questions from the PI or research team at the end of
the inspection. This is an opportunity for the PI to discuss any issues of
non-compliance or other identified issues and provide appropriate
clarification.
(6)
The clinical research auditor will complete a formal
internal audit report after the inspection and provide a copy to the PI within
ten business days. The auditor will evaluate the areas of study conduct that
include human subject protections, protocol and regulatory compliance, validity
and accuracy of data, drug and/or device accountability and will assign a
preliminary internal audit rating at the conclusion of the inspection. The
clinical research auditor may notify the reviewing IRB and/or the appropriate
university official(s) of any findings as necessary for the protection of human
subjects or compliance with university policies. The PI will have fifteen
business days to respond back to the clinical research auditor. Copies of the
final internal audit report will go to the dean of the relevant college, the
vice president of research, and the executive director of internal audit and
chief compliance officer.
(7)
Internal audit ratings:
(a)
Exceptional:
evidence of consistent good clinical practice ("GCP")
compliance.
(b)
Acceptable: only a few minor deviations
noted.
(c)
Deficient: major protocol violations identified.
Requires a written corrective action plan from the PI addressing all areas that
require improvement within ten business days.
(d)
Unacceptable:
requires immediate action and a written response from the PI within five
business days, including the specific date by which the compliance plan will be
fully implemented. The clinical research auditor will immediately notify the
appropriate individuals such as the IRB chair or designated IRB contact person,
vice president of research, and/or the dean of the relevant college of any
suspected human subject safety issue(s) and/or any potential fraud or
fabrication violations. The IRB or university officials may take immediate
action including suspending enrollment or closing the study, if deemed
necessary.
(8)
Documentation of all internal audits along with PI and
IRB/university officials' response (if applicable) will be kept confidential to
the extent permitted by law and maintained in the JCCTR internal audit
files.
