UNIVERSITY OF NEBRASKA MEDICAL CENTER
EPPLEY CANCER CENTER
AUDIT COMMITTEE
POLICIES AND PROCEDURES
1st Edition: Version 3.0, August 11, 2008
Revised: Version 3.1, March 7, 2011
Version 3.2, December 15, 2011
Version 3.3 July 10, 2012
CONTACT INFORMATION
ASSOCIATE DIRECTOR for CLINICAL RESEARCH
Julie M. Vose, M.D.
DATA and SAFETY MONITORING COMMITTEE (DSMC) CHAIR
Elizabeth A. Reed, M.D.
AUDIT COMMITTEE MEMBERS
M. Anne Kessinger, M.D.
Karen L. Schumacher, Ph.D.
EPPLEY CANCER CENTER
PROTOCOL REVIEW and MONITORING SYSTEM OFFICE STAFF
Julie A. Maloney, CCRP
PRMS/CPDMU Administrator
Eppley Science Hall 10007
(402) 559-4232 office
(402) 559-4970 fax
Jennifer Goodwin, BS, CCRC
Regulatory Specialist/Auditor
Eppley Science Hall 1006
(402) 559-4935 office
(402) 559-4970 fax
PRMS WEBSITE
http://www.unmc.edu/ccto
Mirna Colón, BS
Regulatory Data Associate
Eppley Science Hall 10018
(402) 559-4969 office
(402) 559-4970 fax
SECTION B: AUDIT COMMITTEE
ADMINISTRATIVE POLICIES AND PROCEDURES
PURPOSE
PROTOCOLS AUDITED
PROTOCOLS NOT AUDITED
AUDIT FREQUENCY
METHODS
NOTIFICATION OF AUDIT FINDING
Audit Committee Members
Principal investigator (PI)
Scientific Review Committee (SRC)
Other
DURATION OF AUDITS
COMMITTEE MEMBERSHIP AND LENGTH OF TERMS
CURRENT MEMBERS
MEETINGS
AUDIT PROCEDURES
THE ROLE OF THE PRMS OFFICE
THE ROLE OF THE AUDITOR
DATE OF ENROLLMENT
AUDITING OF MULTI-SITE TRIALS WITH UNMC AS THE SPONSOR
PHASE I TRIALS AT UNMC AFFILIATE SITES
ACCEPTABLE SOURCE DOCUMENTATION
PROTOCOL SPECIFIC AUDIT REPORT FORM
AUDIT DOCUMENTATION
INTERNET AND OPEN FORUM COMMUNICATIONS
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APPENDIX B.1: POLICIES AND PROCEDURES FOR MULTI-SITE TRIALS WITH
AFFILIATE SITES AND FOR MULTI-CENTER TRIALS WITH PARTICIPATING SITES
DEFINITION
SUBJECTS AUDITED
AUDIT FREQUENCY
DURATION OF AUDITS
INSTITUTIONAL REVIEW BOARD
AUDITING OF MULTI-CENTER TRIALS WITH UNMC AS THE SPONSOR
PHASE I TRIALS AT UNMC AFFILIATE SITES
ACCEPTABLE SOURCE DOCUMENTATION
AUDIT RESPONSIBILITIES
UNMC Principal Investigator (PI) and/or Their Designee
Affiliate or Participating Site Study Coordinator
UNMC Eppley Cancer Center PRMS Office
UNMC Eppley Cancer Center Auditor
AUDIT COMMITTEE DOCUMENTATION
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SECTION B: UNMC EPPLEY CANCER CENTER AUDIT COMMITTEE
I.
ADMINISTRATIVE POLICIES AND PROCEDURES
A.
PURPOSE
The Audit Committee performs audits and provides oversight on all UNMC Cancer Center
Investigator-Initiated, Multi-Center and Other Externally Peer Reviewed clinical trials. The Audit
Committee assures compliance with institutional regulatory guidelines, confirmation of subject
eligibility, adherence to treatments, appropriateness of adverse event monitoring and reporting,
and adequacy of subject follow-up as stipulated in the protocol.
B.
PROTOCOLS AUDITED
All therapeutic intervention cancer protocols that are Investigator-Initiated, Multi-Center or Other
Externally Peer Reviewed and are not monitored by an external review body are audited by the
committee.
C.
PROTOCOLS NOT AUDITED
All therapeutic intervention cancer protocols that are Investigator-Initiated, Multi-Center or Other
Externally Peer Reviewed and that are monitored by an external review body, such as the
Industrial sponsor or it’s designee, or by an NCI-funded cooperative group are not audited by the
committee.
D.
AUDIT FREQUENCY
While any cancer-related protocol involving human subjects may be at risk for audit at any time
by the audit committee, Investigator-Initiated, Multi-Center or Other Externally Peer Reviewed
protocols are audited at least annually. The frequency of audit is dependent upon the phase of
the protocol. Audits are scheduled based on the protocol’s type of phase.
1. Pilot, Phase I, Phase II and BMT trials – audited at least 4 times per year
2. Phase III trials – audited at least 3 times per year
E.
METHODS
Subjects are selected at random from all eligible subjects enrolled and not previously audited to
protocol scheduled for audit. Protocol related source documents and case report forms (CRF's)
are reviewed and evaluated for the following criteria:
1. Compliance with informed consent and eligibility requirements
2. Treatment administration according to protocol guidelines
3. Toxicity and adverse event reporting
4. Appropriate follow-up
Hospital records, as well as the subject's shadow chart and research file, will be utilized. A
subject specific audit summary will be completed, with any major deviations explained in detail.
Ten (10) percent of the eligible subjects enrolled, with a minimum of one (1) subject, are audited
during each scheduled audit.
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F.
NOTIFICATION OF AUDIT FINDINGS
1. Audit Committee Members: Audit results, using the protocol-specific audit report forms, are
distributed to all members of the Audit Committee in advance of their scheduled meetings.
The committee meets monthly to review the audit report(s) and to review the source
documents and protocol if needed.
2. Principal Investigator (PI): The Audit Committee notifies the PI in writing of the audit
findings. The Audit Committee may request further information and/or follow-up from the PI.
Typically a PI’s written response to this request is expected within three (3) weeks, although
a more timely response may be required in some circumstances.
3. Scientific Review Committee (SRC): Audit findings are reported to the SRC on a monthly
basis. If significant concerns are documented that are thought to compromise the safety or
scientific integrity of the protocol (i.e. failure to comply with the approved study guidelines
regarding adverse event reporting, eligibility criteria, stopping rules, quality data collection,
etc.) the Associate Director for Clinical Research or a member of the Audit Committee can
request that the SRC evaluate the audit and determine if 1) the protocol should be
suspended until the issues are adequately addressed by the PI, 2) the study must be closed,
or 3) if the study can continue.
4. Other: A copy of the letter notifying the PI of the audit findings is sent to the IRB. Audit
findings are also reported to the Director of the Eppley Cancer Center and to the Associated
Director for Clinical Research on a monthly basis.
G.
DURATION OF AUDITS:
All Investigator-Initiated, Multi-Center or Other Externally Peer Reviewed therapeutic intervention
protocols will continue to be audited while subjects are receiving protocol-specific treatment.
Protocols will no longer need to be audited when subject accrual, treatment, and/or research
related tests are completed.
H.
COMMITTEE MEMBERSHIP AND LENGTH OF TERMS:
The Associate Director of Clinical Research appoints the Chair and members to the committee
for a three year term, which can be renewed. The Audit Committee consists of at least three
UNMC Cancer Center members.
I.
CURRENT MEMBERS :
Elizabeth Reed, M.D. – Audit Committee Chair and Professor, Adult Oncology/Hematology
M. Anne Kessinger, M.D. – Professor, Adult Oncology/Hematology
Karen Schumacher, Ph.D. - Associate Professor, College of Nursing
J.
MEETINGS:
The Audit Committee routinely meets on a monthly basis to review audited protocols.
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II. AUDIT PROCEDURES
A. THE ROLE OF THE PRMS OFFICE
1. Orients new members to the Audit Committee.
2. Develops the annual audit schedule.
3. Sends the first notification of the impending audit at least 60 days prior to the scheduled
audit date to the PI and the Study Coordinator, along with the current accrual list to be
reviewed by the study coordinator/data manager for any updates or corrections and
additional of off study dates.
4. Makes necessary accrual updates and corrections in the CTO database.
5. Selects at least one (1) randomly selected eligible subject record to audit, but no more than
ten (10) percent of the total eligible subjects.
6. Sends the second notification of the scheduled audit to the PI and the Study Coordinator
identifying the specific subject(s) to be audited.
7. Creates the agenda and minutes for the audit committee meetings.
8. Reviews the protocol-specific audit report and completes the adverse event reporting
compliance section of the report.
9. Distributes the Audit Committee agenda and minutes, the SRC and DSMC report, copies of
responses received from PI's and the audit reports to the audit committee members for
review.
10. Attends the audit committee meeting
11. Generates the audit finding letter, which is reviewed and signed by the Audit Chair and
distributes the letter to the PI, Study Coordinator, the Associate Director of Clinical Research,
and the IRB.
12. Ensures that a copy of the Audit Committee Policies and Procedures is available at all Audit
Committee meetings.
B. THE ROLE OF THE AUDITOR
1. Generates a protocol-specific audit report to use in performing the audit, conducts the audit
and completes the audit report.
2. Discusses the audit findings and any deviations in protocol with the PRMS Administrator
prior to the monthly meeting.
3. Answers any questions the committee may have regarding the audit report as needed.
C. DATE OF ENROLLMENT
For auditing purposes, the date of consent will be considered the date of enrollment. However,
all eligibility criteria do not need to be met until the date of the first study related treatment.
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D. AUDITING OF MULTI-SITE TRIALS WITH UNMC AS THE SPONSOR
1. For Multi-site trials with UNMC affiliates - Please reference the "PRMS Audit Committee
Affiliate Polices and Procedures" dated 09/03/2010.
2. For Multi-site trials where the participating site(s) are NCI Designated Cancer Centers - The
participating site's Auditor will be expected to conduct the audit and submit an audit report to
the UNMC Audit Committee for review on a schedule to be determined by the UNMC Audit
Committee. Any request for a deviation from this requirement must be submitted to the Audit
Committee in writing and approved by the UNMC Audit Committee prior to enrollment of the
first subject at the participating site(s).
3. For Multi-site trials where the participating site(s) are not NCI Designated Cancer Centers The audit process will be determined on a protocol-by-protocol basis.
4. A copy of the participating site’s audit policies and procedures must be submitted to the
UNMC Audit Committee if the participating site is conducting their own audit and submitting
an audit report to the UNMC Audit Committee for review. The copy of the policies and
procedures should be submitted to the UNMC Audit Committee prior to the first subject being
enrolled at their site prior to enrollment of the first subject at the participating site(s).
E. PHASE I TRIALS AT UNMC AFFILIATE SITES
In addition to randomly selecting at least 10% of the subjects enrolled on Phase I multi-site trials
for audit, all subjects consented to Phase I trials at UNMC affiliate site(s) will also be selected for
audit.
F. ACCEPTABLE SOURCE DOCUMENTATION
1. Case Report Forms (CRF’s) alone, including those generated by C3D via caBIG, are not
considered sufficient source documentation for the purpose of audit.
2. For the purpose of audit, the Medication Administration Record (MAR) and/or the Nurse
Administration sheet will qualify as sufficient source documentation for IV chemotherapy
drugs. The MD prescription is needed as source documentation for oral drugs. (per June
2009 minutes). When the MD prescription is not available, the reason should be
documented within the source documents.
3. All source documentation for the research subject should be placed in the shadow chart or
research file. This includes the subject’s medical records related to the research study that
are located in the UNMC electronic medical record. The copies of the subject’s medical
records should be certified original documents. The UNMC PRMS auditor will not audit the
research file or CRF’s using the UNMC electronic medical record.
G. PROTOCOL-SPECIFIC AUDIT REPORT FORM
The protocol-specific audit report is derived from the following information contained within the
protocol:
1.
2.
3.
4.
Compliance with informed consent and eligibility requirements
Treatment administration according to protocol guidelines
Toxicity and adverse event reporting to the IRB and to the DSMC
Appropriate follow-up
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H. AUDIT DOCUMENTATION
All audit documentation is secured by double locks and maintained in the UNMC Eppley Cancer
Center Clinical Trials Office, Room 10007 of the Eppley Science Hall.
I.
INTRANET AND OPEN FORUM COMMUNICATIONS
Current Policies and Procedures of the PRMS Audit Committee are available thru the UNMC
Eppley Cancer Center PRMS Office or on their web site at http://www.unmc.edu/ccto/.
Periodic open forums are scheduled with study coordinators and PIs to communicate and clarify
audit procedures and obtain feedback to streamline and facilitate the audit process.
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APPENDIX B.1: AUDIT POLICIES AND PROCEDURES FOR MULTI-SITE TRIALS WITH
AFFILIATE SITES AND FOR MULTI-CENTER TRIALS WITH PARTICIPATING SITES
A. DEFINITION
An Affiliate Site is defined as a hospital, clinic, or other provider of medical services who has
been granted a limited license to use the designation “an AFFILIATE of the Eppley Cancer
Center” for purposes reasonably related to oncology research conducted pursuant to an “Affiliate
Agreement”.
A Participating Site is defined as a hospital clinic, or other provider of medical services who has
agree to participate in a therapeutic trial that has been designed and developed by a University
of Nebraska Medical Center/Nebraska Medical Center (UNMC/NMC) investigator and is
sponsored by UNMC.
B. SUBJECTS AUDITED
All subjects consented at an Affiliate or Participating Site to UNMC therapeutic intervention
cancer protocols that are classified by the Eppley Cancer Center Scientific Review Committee
(SRC) as Investigator-Initiated Institutional or Multi-Center Institutional sponsored by UNMC are
audited by the UNMC Eppley Cancer Center Audit Committee (Audit Committee). Trials
classified as Other Externally Peer Reviewed (OEPR) and that are not audited by an external
review body are also audited by the Audit Committee.
Subjects consented to studies that are monitored by an external review body, such as the
Industrial sponsor or its designee, or by an NCI-funded cooperative group are not audited by the
committee.
C. AUDIT FREQUENCY
While any subject consented at an Affiliate or Participating Site to a cancer-related protocol
involving human subjects may be at risk for audit at any time, subjects consented at an Affiliate
or Participating Site to trials falling under the purview of the Audit Committee are audited at least
annually. The frequency of audit is dependent upon the phase of the protocol:
1. Pilot/Feasibility, Phase I, Phase II and BMT trials – audited at least 4 times per year
2. Phase III trials – audited at least 3 times per year
D. DURATION OF AUDITS
All subjects consented at an Affiliate or Participating Site trials falling under the purview of the
Audit Committee will continue to be audited while subjects are receiving protocol-specific
treatment. Subjects will no longer be audited when subject accrual, treatment, and/or research
related tests are completed.
E. INSTITUTIONAL REVIEW BOARD
If the Affiliate or Participating Site does not have their own IRB, the UNMC Institutional Review
Board (IRB) will be the IRB of record for protocols conducted at an Affiliate or Participating Site.
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F. AUDITING OF MULTI-CENTER TRIALS WITH UNMC AS THE SPONSOR
1. Protocols for all Multi-center trials with participating sites and with UNMC as the lead site
must clearly outline the auditing requirements and procedures for all participating site(s).
2. Protocol sections pertaining to these auditing requirements and procedures must be
approved by the UNMC Audit Committee prior to SRC review and approval.
3. For Multi-site trials where the participating site(s) are NCI Designated Cancer Centers - The
participating site's Auditor will be expected to conduct the audit and submit an audit report to
the UNMC Audit Committee for review on a schedule to be determined by the UNMC Audit
Committee. Any request for a deviation from this requirement must be submitted to the Audit
Committee in writing and approved by the UNMC Audit Committee prior to enrollment of the
first subject at the participating site(s).
4. For Multi-site trials where the participating site(s) are not NCI Designated Cancer Centers The audit process will be determined on a protocol-by-protocol basis.
5. A copy of the participating site’s audit policies and procedures must be submitted to the
UNMC Audit Committee if the participating site is conducting their own audit and submitting
an audit report to the UNMC Audit Committee for review. The copy of the policies and
procedures should be submitted to the UNMC Audit Committee prior to the first subject being
enrolled at their site prior to enrollment of the first subject at the participating site(s).
G. PHASE I TRIALS AT UNMC AFFILIATE SITES
In addition to randomly selecting at least 10% of the subjects enrolled on Phase I multi-site trials
for audit, all subjects consented to Phase I trials at UNMC affiliate site(s) will also be selected for
audit.
H. ACCEPTABLE SOURCE DOCUMENTATION
Case Report Forms (CRF’s) alone, including those generated by electronic medical records, are
not considered sufficient source documentation for the purpose of audit.
For the purpose of audit, the Medication Administration Record (MAR) and/or the Nurse
Administration sheet will qualify as sufficient source documentation for IV chemotherapy drugs.
The MD prescription is needed as source documentation for oral drugs. (per June 2009
minutes). When the MD prescription is not available, the reason should be documented within
the source documents.
All source documentation for the research subject should be placed in the shadow chart or
research file. This includes all of the subject’s medical records related to the research study that
are located in the UNMC electronic medical record. The copies of the subject’s medical records
should be certified original documents. The UNMC PRMS auditor will not audit the research file
or CRF’s using the UNMC electronic medical record.
I.
AUDIT RESPONSIBILITIES
1. UNMC Principal Investigator (PI) and/or Their Designee:
a. Conducts a Study Initiation Visit prior to opening a protocol to accrual at the Affiliate or
Participating Site. This visit may be conducted on site or via teleconference and should
involve all Affiliate or Participating Site Investigator(s) and study personnel. The purpose
of the visit is to discuss in detail the implementation of the protocol, reporting
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requirements, and the responsibilities of Affiliate or Participating personnel. The date,
content and attendance at the Study Initialization Visit should be documented and
maintained in the study's records.
b. Provides ongoing guidance and direction as needed to the Affiliate or Participating Site
PI and Study Coordinator regarding protocol specific subject accrual, treatment, and/or
research related tests.
c. Submits protocol, data collection and case report forms to the UNMC Scientific Review
Committee (SRC), Audit Committee and Data and Safety Monitoring Committee (DSMC)
for approval.
d. Provides the approved protocol, data collection and case report forms to the Affiliate or
Participating Site.
e. Forwards the second notification identifying the specific subject(s) to be audited during the
scheduled audit to the Affiliate or Participating Site PI and Study Coordinator and ensures
that all source documentation described in Section VI.B.3 below is submitted for audit.
2. Affiliate Or Participating Site Study Coordinator:
a. Sends a copy of the consent form for each subject registered to the protocol, with
subject name, date of birth, gender, ethnicity and UNMC/NMC medical record number (if
applicable) to the UNMC Eppley Cancer Center Protocol Review and Monitoring (PRMS)
Office within one week of enrollment.
b. Works with the Auditor to schedule a mutually acceptable date and time to conduct an
on-site audit of subject medical records selected for audit.
c. Ensures that hospital charts and any protocol-specific patient records, including a copy
of the protocol that corresponds with the time the subject was entered on study is
available at the on-site audit.
d. Acts as liaison between the Auditor and the Affiliate or Participating Site PI and/or
Consenting MD as needed.
e. Following the completion of the audit, ensures that appropriate follow-up and/or changes
are completed as requested by the Audit Committee.
f. Ensures that data is collected per the standardized data collection form.
3. UNMC Eppley Cancer Center PRMS Office:
a. Provides coordination/training to the Affiliate or Participating Site Study Coordinator prior
to opening a protocol to accrual at Affiliate or Participating Site.
b. Provides ongoing guidance and direction as needed to the Affiliate or Participating Site
Study Coordinator.
c. Sends the first notification of the impending audit to the UNMC Site PI and Study
Coordinator and to the Auditor at least 30 days prior to the scheduled audit date, along
with the current accrual list to be reviewed by the UNMC Site Study Coordinator/Data
Manager for any updates or corrections and addition of off study dates
d. Makes necessary accrual updates and corrections in the PRMS database
e. Selects at least one (1) randomly selected eligible subject record to audit, but no more
than 10% of the total accrual of those subjects registered at the Affiliate or Participating
Site.
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f.
Sends the second notification of the scheduled audit to the UNMC Site PI and Study
Coordinator and to the Auditor identifying the specific subject(s) to be audited.
g. Emails the Audit Committee agenda and minutes, the SRC and DSMC report and the
audit reports to the audit committee members for review.
h. Attends the Audit Committee meeting.
i. Creates the agenda and minutes for the audit committee meetings.
j. Generates the audit finding letter which is reviewed and signed by the Audit Chair and
distributes the letter to the UNMC PI, study coordinator(s), the Associate Director of
Clinical Research, and the IRB.
k. Ensures that a copy of the Affiliate or Participating, Audit Committee and DSMC Policies
and Procedures is available at all Audit Committee meetings.
l. Develops an annual audit schedule.
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4. UNMC Eppley Cancer Center Auditor:
a. Conducts the on-site audit of subject(s) medical records selected for audit from those
registered at the Affiliate or Participating Site.
b. Generates a protocol-specific audit report form to use in performing the audit, conducts
the audit and completes the audit report
c. Attends the audit committee meetings to discuss the audit findings and any deviations in
protocol.
J. AUDIT COMMITTEE DOCUMENTATION
All audit documentation will be maintained in the UNMC Eppley Cancer Center Protocol Review
and Monitoring (PRMS) Office, Room 10007 of the Eppley Science Hall. In addition, copies of all
audit related documents will be maintained at the Affiliate or Participating Site and be available to
the Auditor at all times.
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