**[Multi-Institutional Monitoring Plan (MIMP) Template
INSTRUCTIONS]{.underline}**

DCP Version Date: March 31, 2008

**[Instructions:]{.underline}** The Consortium Lead Organization (CLO)
Principal Investigator and Site Coordinator should review the **MIMP
Template** and make any changes that are necessary to meet institutional
requirements within sixty calendar days of the DCP Version Date. The CLO
Principal Investigator and Site Coordinator will track any changes
within the document (if necessary), complete the cover page of this
document and submit this to the DCP Protocol Information Office
(<NCI_DCP_PIO@mail.nih.gov>) and the DCP Help Desk
(nci-dcpmonitoring@westat.com). DCP will inform the CLO Principal
Investigator, Site Coordinator and the DCP Help Desk of the status by
email. Once approved by DCP, the Consortium-specific MIMP will be
maintained electronically by the CLO, DCP-PIO, and DCP Help Desk.

The new DCP approved consortium-specific MIMP will apply to all
subsequent studies and will be part of the Additional Study Related
Documents submitted with each [new]{.underline} protocol.  The MIMP will
be referenced in the Protocol Submission Worksheet for subsequent
revisions or amendments to the protocol. Protocol-specific modifications
will only be submitted in rare cases, as a Master MIMP Addendum. The
Addendum will come as an attachment to the Protocol Submission
Worksheet. Throughout the MIMP document, Standard Operating Procedures
(SOPs) are referenced.  The SOPs provide a more detailed description of
required Consortia procedures.

Site Information

  ------------------ ----------------------------------------------------
  CLO Institution        
  Name:              

  Contract Number:       
  ------------------ ----------------------------------------------------

**[MIMP Modification]{.underline}**

Were institutional requirement modifications made to the document?

Yes, changes are tracked within the document

No

**[Form Completed by:]{.underline}**

  -----------------------------------------------------------------------

  **CLO Principal Investigator** (Name) (Date)

  (Email Address)

  **CLO Site Coordinator** (Name) (Date)

  (Email Address)
  -----------------------------------------------------------------------

***FOR DCP USE ONLY:***

[**DCP MIMP Approval**:]{.underline}

Yes

No Reasons for Disapproval:

  -----------------------------------------------------------------------

  **DCP Project Officer** (Name) (Date)
  -----------------------------------------------------------------------

**[Multi-Institutional Monitoring Plan Template\
]{.underline}**

# I. Overview

The Consortium Lead Organization (CLO) is the lead organization of a
consortium of clinical research sites that will conduct cancer
chemoprevention Phase I and II studies for the Division of Cancer
Prevention (DCP) of the National Cancer Institute (NCI). The CLO will be
responsible for all administrative, protocol initiation and protocol
implementation activities, and will ensure the protection of human
subjects, and study data authenticity, integrity, and confidentiality,
in compliance with federal regulations and DCP requirements (as stated
in the DCP approved MIMP Template and DCP approved Standard Operating
Procedures (SOPs)). The Multi-Institutional Monitoring Plan (MIMP) was
created to describe the oversight and management responsibilities of the
CLO.

# II. Introduction 

1.  The ***\[contractor institution name\]*** is the CLO under contract
    ***\[number\]***. The consortium may include DCP approved
    Participating Organizations (POs). Additional sites may only be
    added after approval by DCP.

2.  The CLO acts as the primary liaison with DCP and is responsible for
    overseeing the conduct of each study protocol and monitoring the
    progress at all POs and the CLO site if applicable.

3.  The CLO Principal Investigator (PI) may delegate responsibilities
    for monitoring as defined by DCP, to the CLO Site Coordinator or to
    another qualified individual. This delegation of responsibility
    should be documented and maintained in the CLO's regulatory file.
    The person designated to conduct on-site monitoring activities will
    satisfy the training requirements as outlined and approved by DCP.
    (Refer to SOP #1 "Identifying Staff to Conduct On-Site Monitoring
    Visits for the DCP Prevention Consortia.")

# III. Protocol Pre-Activation Activities

# A. Protocol Development

# The CLO acts as the primary liaison with DCP. As the liaison, the CLO will be responsible for all communications with the DCP Protocol Information Office (PIO) regarding the study protocol. The CLO PI and Site Coordinator will also be responsible for disseminating relevant information gathered from the DCP PIO to the POs that will be participating in the study.

# The Consortium Principal Investigator and CLO Site Coordinator will be responsible for the following: 

-   Protocol and protocol budget development;

-   Protocol and protocol budget submissions to DCP for review;

-   Receipt and distribution of DCP review comments to appropriate POs;
    and

-   Ensuring that appropriate local regulatory documents have been
    obtained by POs. (Refer to SOP #3 "Collection and Submission of
    Regulatory Documents.")

3.  The CLO will evaluate the feasibility of recruitment and retention
    (R & R) to each proposed protocol during the Letter of Intent (LOI)
    phase of protocol development. At the time of protocol development,
    the CLO will submit to DCP a plan for R & R that addresses the
    unique populations of the POs and the CLO.

4.  It is recommended that early in the protocol pre-activation phase,
    the PO Site Coordinators submit study-specific R & R plans to the
    CLO for review. All plans should include alternative strategies.
    (Refer to SOP #9 "Review and Tracking of Recruitment, Retention and
    Adherence Plans at POs.")

5.  The CLO will evaluate R & R on an ongoing basis and provide feedback
    to the PI and Site Coordinators at the POs.

    **B. Protocol Initiation**

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1.  The CLO Site Coordinator will ensure that the Site Coordinators at
    all POs are provided with the most current version of the protocol
    with consent form and all protocol related documents and guidelines.
    (Refer to SOP #12 "Conducting a CLO-Led Study Initiation Visit.")

    **C. Regulatory Requirements**

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1.  All Site Coordinators at the CLO and POs are required to prepare and
    submit regulatory documents prior to study initiation throughout the
    lifecycle of the study.

2.  The Site Coordinators at the POs will gather their initial
    regulatory documents and submit them to the Site Coordinator at the
    CLO. The PO Site Coordinators will also send updated regulatory
    documents to the CLO Site Coordinator. (Refer to SOP #3 "Collection
    and Submission of Regulatory Documents.")

3.  As the primary liaison with DCP for its consortium, the CLO Site
    Coordinator is responsible for submitting the initial and subsequent
    regulatory documentation for the CLO as well as its POs to the DCP
    Regulatory Contractor.

4.  Once IRB approval is granted, the CLO Site Coordinators will gather
    and submit initial regulatory documentation for their own
    institution regardless of its participation status on a given
    protocol.

5.  The PO and CLO Site Coordinators will gather the following
    regulatory documents before the study is activated:

-   Form Food and Drug Administration (FDA) 1572- Requirements for the
    CLO differ depending on the CLO's participation in a given protocol
    (Refer to SOP #3 "Collection and Submission of Regulatory
    Documents");

-   Signed and dated Curriculum Vitae (CV) and current professional
    license (when applicable) for each investigator and all sub
    investigators listed on the Form FDA 1572;

-   Certification of human subjects protection training for all
    investigators listed on the Form FDA 1572 and other study staff who
    have roles for study operations;

-   Financial Disclosure Form, when applicable, for each investigator
    listed on the Form FDA 1572;

-   Current lab certifications (Clinical Laboratory Improvement Act
    (CLIA), College of American Pathologists (CAP)) and lab normal
    ranges for each laboratory, where work is being conducted on the
    study, listed on the Form FDA 1572;

-   Documentation of Institutional Review Board (IRB) and DCP approval
    for the following:

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-   Protocol with informed consent;

-   Advertisements/Recruitment materials;

-   Any written/educational materials to be provided to the participant;
    and

-   Investigator's brochure (if applicable).

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-   Federal-wide Assurance number.

# D. Study Initiation Visit

1.  The study initiation visit will be conducted after CLO IRB protocol
    submission, and in advance of study activation. The study initiation
    visit will be held at the CLO or via remote conferencing as
    determined by the DCP Medical/Scientific Monitor. The CLO PI may
    delegate responsibilities for monitoring activities including study
    initiation visits to the CLO Monitor.

2.  In most instances, the CLO Monitor will be expected to conduct all
    initiation visits for each protocol even if the CLO is not the lead
    on a particular protocol. The DCP Monitoring Contractor may conduct
    study initiation visits as decided by DCP. Usually, the initiation
    visit will be a full day meeting.

3.  The PIs and Site Coordinators for both the CLO and POs accruing to
    the study should attend the study initiation visit. If PO personnel
    are unable to attend the initiation visit in person, they will be
    asked to attend via audio and/or video conference. If PO personnel
    are unable to attend the study initiation visit in person or via
    remote conferencing, or on the rare occasion when an additional PO
    is added after the study initiation visit has taken place, the CLO
    Monitor will be responsible for conducting a separate PO study
    initiation visit.

4.  The CLO Monitor will prepare an initiation visit report for the
    study initiation visit and any separate PO study initiation visits
    for submission to the DCP Medical/Scientific Monitor. (Refer to SOP
    #12 "Conducting a CLO-Led Study Initiation Visit.")

5.  Prior to planning the study initiation visit, the CLO Monitor is
    strongly advised to schedule a strategy meeting as a forum for all
    study staff, especially the PIs, to address any issues that could
    result in amendments to the protocol.

6.  The PIs, Co-Investigators, and Site Coordinators at the CLO and POs
    will be prepared to discuss the procedural as well as the scientific
    aspects of the protocol during the visit. (Refer to SOP #12
    "Conducting a CLO-Led Study Initiation Visit" for a list of protocol
    initiation topics.)

# IV. Active Protocol-Related Activities 

#### A. Protocol Implementation Preparation

1.  At their respective sites, the CLO and PO PI, Investigators, and
    Site Coordinators will be responsible for ensuring IRB approval of
    the study at the CLO and POs, obtaining informed consent, verifying
    participant eligibility, and registering all participants on study.

2.  The CLO and PO PI, Investigators, and Site Coordinator will be
    responsible for assessing participant eligibility at their
    respective sites throughout the lifecycle of the study.

3.  The CLO Site Coordinator will be responsible for ensuring that the
    Site Coordinator(s) at the PO(s) has completed protocol-specific
    training (if needed) prior to the implementation of a study.

4.  The CLO Site Coordinator will ensure regular communications with the
    PO Site Coordinators regarding current protocol and Case Report Form
    (CRF) versions, forms, procedures, changes in study-related
    materials, and issues for protocol implementation. (Refer to SOP #2
    "Communication with POs Regarding Forms, Procedures, and Other
    Items.")

5.  The CLO PI, Investigators, and Site Coordinator will be responsible
    for evaluating participant R & R on an ongoing basis and provide
    feedback to the PO PI and Site Coordinator.

#### B. Protocol Maintenance

1.  The CLO PI and Site Coordinator will be responsible for ensuring the
    PO PIs, Investigators, and Study Coordinators are using the correct
    version of the protocol and CRFs as approved by DCP and the
    respective IRBs.

2.  The CLO PI and Site Coordinator will be responsible for all DCP
    reporting requirements.

3.  Each Consortium will have staff at both the CLO and each PO who are
    designated to perform data entry (DE) and data quality assurance
    (QA); however, an exemption can be requested that will still retain
    data quality. This exemption must be approved by DCP, and once
    granted, the approval message must be kept on file at the CLO. The
    indication that data have been reviewed from source documentation to
    paper CRF to electronic CRF and all discrepancies are resolved in
    the DCP Oracle Clinical (OC)-Remote Data Capture (RDC) database by
    using the "Approval" feature. A delay in full implementation of DCP
    OC-RDC should not obviate regular QA of paper-based data.

4.  The designated CLO Monitor(s) will be responsible for quality
    control of study data by reviewing subject records in association
    with site monitoring visits. (See also DCP SOP #24 "Monitoring of
    DCP OC-RDC Data at the POs.") The indication that data have been
    reviewed and verified by the monitor is use of the database "Verify"
    feature. A delay in full implementation of DCP OC-RDC should not
    delay regular monitoring of paper-based data.

5.  The CLO and/or PO PI and Site Coordinator will be responsible for
    reviewing and reporting all AEs and SAEs to DCP.

6.  The CLO Site Coordinator will be responsible for contacting the PO
    Site Coordinator for participant accrual numbers every fourteen
    calendar days. The CLO Site Coordinator will review the R & R plan
    regularly throughout the course of the study. The CLO Site
    Coordinator may need to provide feedback and suggestions to the PO
    Site Coordinator and PI if accrual results are not as anticipated.

7.  The CLO PI and Site Coordinator will be responsible for overseeing
    the activities of the POs from the CLO office (off-site monitoring).
    The requirements include, but are not limited to, the following:

-   Review all the recruitment, retention, and adherence plans for each
    protocol on an ongoing basis;

-   Track participant accrual for each protocol;

-   Receive, review, and submit regulatory documents to the DCP
    Regulatory Contractor;

-   Assess timely data entry by PO staff via DCP OC-RDC;

-   Review protocol deviations from each PO for each open study;

-   Provide oversight of SAE reporting (Refer to SOP #25 "Reporting and
    Tracking SAEs");

-   Track and report staff changes to DCP; and

-   Assist in troubleshooting other protocol implementation issues.

> (Refer to SOP #7 "Preparing for and Conducting Off-site Monitoring";
> SOP #9 "Review and Tracking of Recruitment, Retention and Adherence
> Plans at POs"; and SOP #10 (ON HOLD) "Collecting, Reporting & Tracking
> Staff Changes at the POs.")

# 

# C. Annual/Interim Monitoring Visit

1.  The CLO PI may delegate responsibilities for on-site monitoring
    activities as defined by DCP to the CLO Monitor. The CLO Monitor
    will be responsible for scheduling and conducting on-site monitoring
    visits of their POs. The CLO Monitor will satisfy the minimum
    training requirements as outlined in SOP #1, "Identifying Staff to
    Conduct On-Site Monitoring Visits for the DCP Prevention Consortia."
    Names and roles of all monitoring designees should be recorded and
    kept with the regulatory files.

2.  The first annual monitoring visit to a PO should occur eight months
    after a study opens or after the first study participants are
    enrolled, whichever occurs first; however, this may be evaluated on
    a case by case basis by the DCP Medical/Scientific Monitor and/or
    DCP Nurse Specialist (The initial annual visit is not justified
    unless there is at least one participant enrolled on a study). The
    DCP Medical/Scientific Monitor and/or Nurse Specialist should be
    notified of the date of the scheduled visit. The CLO Monitor will
    also conduct interim visits as requested by the DCP
    Medical/Scientific Monitor and/or Nurse Specialist. An interim visit
    may be conducted as a follow-up to an annual visit where a number of
    deficiencies were identified, or it may be requested for reasons
    such as the complexity of the study, staff changes, or number of
    subjects enrolled. The CLO Monitor will conduct a close-out visit at
    the end of the study at all participating POs. (Refer to SOP #19
    "Preparing for and Conducting the Close-out Visit at the POs.")

3.  The annual visit is generally scheduled for two and a half days
    on-site. The activities/assessments by the CLO Monitor that will
    take place during the on-site annual visit include, but are not
    limited to the following:

-   Review of regulatory documents;

-   Ensure confidential documents are securely stored according to
    institutional standards;

-   CRF and record review, including DCP OC-RDC-monitoring;

-   Review of pharmacy operations and agent accountability;

-   Discussions regarding site operations; and

-   Summary meeting with study principals to discuss findings and plans
    for improvement (when applicable).

> The duration of an interim visit is between one and a half days and
> two and a half days. During an interim visit, the CLO Monitor will
> focus on the area where the majority of the deficiencies were
> identified or will address other problems or issues noted since the
> last visit. A DCP representative may also choose to attend an interim
> visit at a PO. (Refer to SOP #4 "Conducting the Annual or Interim
> Visit by the CLO at the POs- On-Site Monitoring.")

4.  Scientific advances depend on the reliability of research data. The
    CLO Monitor will be responsible for identifying and reporting any
    suspected fraud and scientific misconduct if discovered during the
    review. The CLO Monitor should be familiar with guidelines that can
    be used in an investigation for detecting fraud or misconduct.
    (Refer to SOP #11 "Detecting and Reporting Suspected Scientific
    Misconduct or Fraud.")

5.  Within forty-eight hours of the completion of an annual site visit,
    the CLO Monitor will send a preliminary report to the DCP
    Medical/Scientific Monitor, the DCP Nurse Specialist, and the DCP
    Monitoring Contractor electronically via email. (Refer to SOP #5
    "Reporting Major and Lesser Deficiencies and Preparing the
    Preliminary Report of Monitoring Findings.")

6.  The CLO Monitor will submit a draft Clinical Site Annual Visit
    Report and Pharmacy Audit Report including a list of action items
    and associated reports if applicable to the DCP Medical/Scientific
    Monitor and DCP Nurse Specialist within fourteen calendar days of
    the visit. DCP has fourteen calendar days to review the draft and
    provide comments to the CLO Monitor. Upon receipt of the comments,
    the CLO Monitor will have seven calendar days to respond to DCP
    comments and finalize the report. The CLO Monitor then signs the
    final DCP approved report and distributes a hard copy to the CLO
    Principal Investigator, and scanned PDF versions to the DCP
    Medical/Scientific Monitor, the DCP Nurse Specialist, DCP PIO, DCP
    Project Officer, the DCP Monitoring Contractor (DCP Help Desk) and
    the DCP Regulatory Contractor.

7.  The PO staff will follow up on findings and action items from the
    annual/interim visit and will send written follow up of action items
    to the CLO within thirty calendar days of receipt of the site visit
    report. The CLO will forward this information to DCP.

# V. Training

1.  The CLO Site Coordinator will assure that the POs' site staff have
    completed Human Subject Protection training provided by the Office
    for Human Research Protections (OHRP) or a comparable
    institution-specific training.

2.  The CLO PI and Site Coordinator will assure that the CLO Monitor is
    adequately trained for designated monitoring responsibilities.
    (Refer to SOP #1 "Identifying Staff to Conduct On-Site Monitoring
    Visits for the DCP Prevention Consortia.")

3.  The CLO Site Coordinator will ensure that the appropriate person(s)
    from the Consortium completes the DCP OC-RDC training.

4.  The CLO Site Coordinator will also report additional staff training
    needs to DCP via the Clinical Site Annual or Interim Visit Report.
    (Refer to SOP Appendix #1 "Clinical Site Annual or Interim Visit
    Report.")