Clinical Data Monitoring Plan [COMPANY] Protocol [0000]

Version: 1 Date: [DATE]

CLINICAL DATA MONITORING PLAN (CDMoP)

PROTOCOL # [0000]

[TITLE]

CONTRACT RESEARCH ORGANIZATION

SPONSOR
[NAME]
[ADDRESS]

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 Clinical Data Monitoring Plan [COMPANY] Protocol [0000]

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TABLE OF CONTENTS

1. Purpose 3
2. References 3
3. Study Roles and Responsibilities 3
4. Tools and Processes 4
4.1 Study Data 4
4.2 EDC Monitoring Module 4
5. Risk Mitigation Strategy 5
6. Source Documents 7
7. Monitoring 7
7.1 Onsite Monitoring 7
7.2 Central Monitoring 8
7.3 Qualification Visit 9
7.4 Site Initiation Visit 9
7.5 Interim Monitoring Visits 9
7.6 Closeout Visit 10

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1. PURPOSE
The purpose of this document is to specify all study specific monitoring requirements for
[COMPANY] Protocol [0000] that ensure that the clinical sites comply with the study
protocol and regulatory requirements.

2. REFERENCES
1. SOP XXXXX: Conducting Initiation, Monitoring and Closeout Visits
2. SOP XXXXX: Site Qualification
3. SOP XXXXX: Trial Master File
4. SOP XXXXX: Investigator Noncompliance
5. EMA Reflection paper on expectations for electronic source data and data
transcribed to electronic data collection tools in clinical trials (2010)
6. EMA Reflection paper on risk based quality management in clinical trials (2013)
7. FDA Draft Guidance for Industry - Computerized Systems Used in Clinical
Investigations (2007)
8. FDA Guidance for Industry - Electronic Source Documentation in Clinical
Investigations (2013)
9. FDA Guidance for Industry - Oversight of Clinical Investigations - A Risk-Based
Approach to Monitoring (2013)

3. STUDY ROLES AND RESPONSIBILITIES

Name Contact Information Role/Responsibility

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4. TOOLS AND PROCESSES

4.1 Study Data

This study will use direct data entry of clinical trial data. This process allows a clinical
study site to perform direct data entry of original data into EDC at the time of the subjects
office visit, and for the original data to be stored in PDF format in the access-controlled
data repository, access to which is controlled by the clinical Investigator or designee.
These original data are stored in the access-controlled data repository prior to the data
being transmitted to the EDC database.

4.2 EDC Monitoring Module

Monitors will record all monitoring reports in the online EDC system.

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5. Risk Mitigation Strategy

Category Risk Severity Probability RPN Risk Mitigation

Instruction for user, site training prior to study, weighing of
Trial Outcome Patient dosing compliance high medium 6 IMP, monitoring by CRO
Trial Outcome Improper blood draw high medium 6 Training and monitoring of [DRUG] levels, online reports

Trial Outcome Blood storage and processing at trial site high medium 6 On site monitoring
Monitoring, and training at interim visit immediately prior to
Trial Outcome Missing blood draws on last day high medium 6 1st patient day 90, online reports
Training and evaluating and resolving reasons for dropout,
Trial Outcome Patient dropouts high medium 6 phone alerts prompted by eCRF, online reports
Training, reinitiate the site, assess the site after three
Both Site staff misunderstanding of the protocol high medium 6 patients treated, investigator meeting,
Real-time monitoring of enrollment rate, allow for open
Trial Outcome Unexpectedly low enrollment rate medium medium 4 enrolment across sites, online reports
Modify titration scheme and cut off based on previous data
prior to study start for [0000], edit check in the eCRF,
Both Incorrect dosing medium medium 4 training, online reports
Both Patient in other clinical trial medium medium 4 Use of verifiedclinical.com
Informed consent, instruction for user, site training prior to
Patient Transfer to other individuals high low 3 study
Auditing and review of data analysis turn around,
Trial Outcome Errors in Bioanalysis at CRO high low 3 communication plan
Trial Outcome Loss of eSource data high low 3 Multiple daily backup and disaster recovery
Central review and sign off patients by CRO when site
confirms eligibility, not allow rescreening, review of medical
Both Improper enrollment of Ineligible patients high low 3 record
Monitoring and review of patient records and medical record,
Both Improper reporting of AEs high low 3 online reports

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Category Risk Severity Probability RPN Risk Mitigation

Trial Outcome Fraud and misconduct medium low 2 Monitoring

Trial Outcome Error in application of IMP medium low 2 Instruction for user, site training prior to study, online reports

Both Increase in safety lab test results medium low 2 Monitoring by investigator and daily by CRO
Both Improper storage of IMP low medium 2 On site monitoring
Both CRO staff qualifications medium low 2 Sponsor oversight
Instruction for user, site training prior to study, drug
Patient Overdose low low 1 accountability, online reports
Both Skin reaction low low 1 Monitoring by investigator and daily by CRO, online reports
Both Use of prohibited conmed low low 1 Monitoring review of medical record, online reports
Both Site out of business low low 1 Contingency plan and proper qualification visit

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6. SOURCE DOCUMENTS
1. Source data/records contain all the information necessary for the reconstruction and
evaluation of the study. Source data/records are 1) original records, 2) certified
copies of original records, 3) observations, 4) laboratory reports, 5) paper Case
Report Forms (CRFs) and/or data sheets. In addition, with the use of direct data
entry, the PDFs maintained in access-controlled data repository serve as original
records. The EDC system and access-controlled data repository also support a
process for certifying copies of records originally captured on paper.
2. At the time of the first monitoring visit or during the initiation visit, the source of
original data, whether it is being collected in electronic or paper format, will be
identified for each site.

7. MONITORING
Onsite monitoring visits will focus on assuring that the clinical site understands and is
following the protocol, reviewing completeness and accuracy of Informed Consent Forms,
drug supply reconciliation, risk-based source document verification (SDV) of original
records, and other issues that may occur during the course of the clinical trial.

Central monitoring will focus on the assessment of 1) the reasonableness of data entered
into EDC system and 2) data quality management metrics

7.1 Onsite Monitoring

All onsite monitoring visits will be planned, but they will not follow a fixed schedule.
For each site, the Project Manager or the responsible monitor, will schedule the first
onsite monitoring visit to coincide with the first PK blood draw (Day 1) for any of the
first three subjects. Based on the findings at this visit, coupled with central
monitoring findings, the Project Manager will decide when to schedule the next
monitoring visit.
For each site, the Project Manager will schedule a monitoring visit immediately prior
to or coinciding with the first subjects 24-hour PK blood draw (Day 90/91). The
purpose of this visit is primarily to retrain the site personnel on the relevant study
procedures.
Interim monitoring visits will include review of the following:
1. Informed Consent process and Forms (100%)
2. Study conduct and protocol adherence
3. Subject Eligibility (100%)
4. Adverse events (100%)
5. Drug supply accountability (100%)
6. Temperature logs
7. Personnel delegation and signature log
8. Patient medical records
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9. Protocol deviations and violations

10. Follow-up of outstanding issues
11. The certification process of data originally collected on paper and
subsequently entered into the EDC system
Where the site maintains patient records that duplicate information captured in the
EDC system, the monitor will review those records specified below to ensure that the
site records match those captured in the EDC system:
1. Demographics (100%). To ensure subject identities based on the sites
medical records
2. Medical History. To ensure the sites have entered into the EDC system all
relevant inclusion/exclusion criteria (100%)
3. Confirmation of subjects visit to the clinical site (100% of first 3 subjects)
4. Review of office medical record (100% of first 3 subjects)
When findings indicate that retraining is required, the monitor must retrain site staff
as soon as possible, and if necessary the site will be informed not to enroll additional
subjects until successful completion of the training.

7.2 Central Monitoring

Monitors will perform daily in the EDC system:
1. 100% review of all entered forms and issue queries if needed
2. Review and take appropriate action for all online and batch edit checks
3. Review of baseline and titration [DRUG] against records received from
central laboratory Levels (100%)
Monitors will issue weekly central monitoring reports to record issues identified
through daily monitoring activities.
Monitors will review periodically the eTMF for accuracy and completeness.
Quality by Design (QbD) meetings will take place on a weekly basis with the Project
Manager, Project Director, Biostatistics (as needed), and Data Management (as
needed) to review the progress of the clinical trial. Items to be reviewed at the QbD
meetings may include:
1. Enrollment and dropout status
2. Number of forms entered and reviewed
3. An assessment of edit checks and queries that are being fired, by form as
well as by variable
4. Reasons for changes to the database by the clinical site
5. Adverse events
6. Medications
7. Protocol deviations and violations
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8. Monitoring Procedures
9. Other items that may arise
10. Action items
The Project Manager will record meeting minutes and follow-up actions. The
schedule of meetings and the Clinical Monitoring Plan may be modified depending
on findings. The decisions and the rationale for changing any of the procedures will
be documented.

7.3 Qualification Visit

The purpose of the qualification visits is to assess the clinical trial sites ability to fulfill the
qualification criteria. Decisions regarding the need for onsite qualification visits will be
made in accordance with SOP XXXXX.

7.4 Site Initiation Visit

The purpose of the study initiation is to train Investigators and site personnel on the
specific requirements and procedures needed to perform the clinical trial.

Site initiation will occur at the Protocol Investigator Meeting (PIM), locally at specific sites
who do not attend the PIM, or if it is determined that a specific site requires additional
training. Sites will not enroll subjects into the trial until the site initiation has been
satisfactorily completed. Delivery of the investigational product may precede the initiation,
but must not be shipped until the study site receives IRB approval.

At a minimum, the agenda for the site initiation visit must include the following elements:

1. Review of the protocol

2. Training appropriate staff on:
a. GCP regulations
b. SAE reporting requirements
c. Investigator on the Investigator responsibilities listed on the FDA Form 1572
d. Investigational product handling procedures
e. Weighing of the Investigational Product
f. Subject management over the course of a 24-hour PK
g. Handling of PK samples
h. Handling of safety laboratory samples
i. EDC system
j. Certification of original records
k. Maintenance of the electronic Trial Master File (eTMF)
l. Direct data entry process

7.5 Interim Monitoring Visits

The purpose of interim monitoring visits is to ensure that the 1) rights and well-being of
each subject are protected, 2) trial data are accurate, complete and verifiable, 3) the trial is
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conducted according to ICH GCP guidelines, and 4) that the trial site and staff remain
trained and qualified. Monitoring of the clinical trial can occur both by onsite visits as well
as through central monitoring procedures.

7.6 Closeout Visit

The purpose of the closeout visit is to bring to official completion all trial-related activities at
the site.

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