Monitoring Plan (Template): Investigator-Initiated Clinical Trials
(Protocol Title)
Protocol Number:
Qualified Investigator (QI):
REB Number:
Sponsor:
Sunnybrook Research Institute
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Prepared By (print):
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Signature
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Date (yyyy-mmm-dd):
______________________ ______________________
Approved By (print QI name): Signature (QI)
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Date (yyyy-mmm-dd):
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Glossary
AE
CRF
DCF
e-CRF
EDC
ICF
ICH-GCP
IP
QI
REB
SOP
SAE
TDL
1.0
Adverse Event
Case Report Form
Data correction Form
Electronic Case Report Form
Electronic Data Capture
Informed Consent Form
International Conference on Harmonization Good Clinical Practice
Investigational Product
Qualified Investigator
Research Ethics Board
Standard Operating Procedure
Serious Adverse Event
Task Delegation Log
Study Overview
(Insert brief study synopsis here (ie. objectives and the critical data/study procedures)
2.0
Purpose
The purpose of trial monitoring is to verify the following:
1. The rights and well-being of human participants are protected
2. The reported trial data are accurate, complete, and verifiable from source documents
3. The conduct of the trial is in compliance with the currently approved protocol/amendment(s),
with GCP, and with the applicable regulatory requirements.
This document identifies key monitoring activities and specifies the data to be reviewed. Study
monitoring is a Sponsor responsibility as outlined in ICH-GCP and has been delegated by Sunnybrook
Research Institute to the Qualified Investigator (QI)/Investigator of the study.
3.0
Monitor
Monitors are responsible for ensuring the appropriate conduct and documentation of a study. As
delegated by the sponsor, monitoring is the responsibility of the Qualified-Investigator (QI), but may be
delegated to an appropriately trained study team member(s). Delegation of this task has been indicated
on the study Task Delegation Log (TDL) and training and qualification documents kept on file. The
monitor is familiar with the investigational product(s) (IPs), protocol, written informed consent form(s)
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(ICFs), internal SOPs, ICH-GCP and Part C, Division 5 of the Food and Drug regulations, Part 4 of the
Natural Health Products regulations.
(Study monitors do not need to be independent of the study team; team members not directly involved in
collecting data or recruiting participants may perform study monitoring as long as they are not
monitoring their own work. Study coordinators from other trials may also monitor each other’s studies. If
the study is multicenter/multinational, this section will also describe how the coordinating centre is
monitoring participating sites.)
4.0
Responsibilities
The monitor is responsible for verifying that:
1.
2.
3.
4.
The study team is following the approved protocol and all approved amendments.
Written informed consent was obtained before each participant is enrolled in the trial.
Only eligible participants are enrolled.
Source documents and other trial records are accurate, complete, kept up-to-date and
maintained.
5. Investigator completes/submits all notifications, applications, and submissions (including Health
Canada and REB submissions), and that these documents are accurate, complete, timely, legible,
dated and that they identify the trial.
6. Accuracy and completeness of the (paper/electronic)CRF entries, source documents and other
trial-related records against each other. Specifically, the monitor will verify that:
a. The data required by the protocol are recorded accurately on the CRFs and are
consistent with the source documents.
b. Any dose modifications are documented for each participant.
c. Adverse events (AEs), concomitant medications and intercurrent illnesses are recorded
in accordance with the protocol on the CRFs.
d. Any protocol deviations (eg.. missed or outside of window visits/tests/examinations
etc.) are clearly recorded as such on the CRFs and reported as required.
e. All participant withdrawals are reported and explained on the CRFs.
f. Ensuring that any corrections, additions or deletions that are made to the CRFs are
dated, explained (if necessary) and initialed by the investigator or a delegate.
g. Determine whether all AEs are appropriately reported within time periods required by
ICH-GCP, the protocol, internal SOPs, local REB, and Health Canada
h. Ensure that the essential documents are maintained for the trial.
i. Communicate deviations from the protocol, internal SOPs, ICH-GCP and the Food and
Drug regulations and take appropriate action to prevent recurrence.
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7. Investigational Product
a. Storage times and conditions (includes temperature monitoring) are acceptable, and
that supplies are sufficient throughout the trial.
b. IPs are supplied and administered at the protocol specified dose(s) only to participants
who are eligible to receive it.
c. There should be a plan to explain to participants how to correctly use and return (if
applicable) the IP .
d. The receipt, use, and return of the IPs at the site are controlled and documented.
e. The disposition of unused IPs at the site complies with applicable regulatory
requirements.
5.0
Procedures
(At minimum, monitoring procedures should include plans for a site initiation visit, at least one interim
monitoring visit and a close-out visit. The “risk-based” approach to monitoring should be used to assess
the need for additional monitoring visits. This approach is based on the research category (clinical
phase/type of research) and risk exposure to participants and the institution.
The FDA draft guidance on the risk-based approach to monitoring is a document that outlines the
principles of risk-based monitoring and may assist you in the customization of your monitoring plan:
FDA Guidance on Risk-Based Approach to Monitoring.)
5.1
Site Initiation
Prior to the start of recruitment, the QI and/or Delegate will conduct a site initiation
meeting/teleconference once the site has received all regulatory and REB approvals. In addition to the
QI and/or delegate for the trial coordinating centre, all study team members for the site should attend
the site initiation meeting.
The QI and/or delegate will conduct the site initiation meeting/teleconference and will cover the items
listed below in order to ensure that all study staff are aware of their delegated duties:
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Protocol
Investigational product
Study-specific SOPs
CRF completion
ICH-GCP compliance
Health Canada regulations
Unanticipated Problems/SAE/AE recording and reporting
Protocol deviation management
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QI and Sub-I responsibilities
The study monitor will generate a brief report on the material covered and any additional training
required. The monitor will forward the report to the site for review and sign-off by the QI no later than
XX weeks/days from the site initiation meeting/conference. Once any issues noted in the initiation
report are resolved, the QI will be notified that the study can be initiated.
5.2
Interim Monitoring Process
(For your study, please modify text as appropriate. Many factors should be taken into consideration
when determining the frequency of monitoring, and timing of the first monitoring visit. Considerations
may include the disease site (ie. oncology may require more frequent monitoring), complexity of the
protocol, target enrollment, number of participant visits, data collected at each visit. Ensure that what
you decide on is practical, as you will need to follow this plan.)
1. The first monitoring visit will be conducted at each site after approximately <insert number of
participants> have been < i.e., screened, enrolled, randomized>
2. Frequency of future monitoring visits will be based on enrollment status, safety concerns, data
quality, and protocol compliance.
3. Monitoring visits will review all of the responsibilities listed above.
4. Following each monitoring visit, a monitoring report will be submitted to the QI and to Quality
Assurance & Education, HRPP at SRI. (See section 7.0 for monitoring report details.)
5.3 Monitoring Visit Activities
The following activities may take place during each monitoring visit:
Data for all participants will be monitored over the course of the trial, but not necessarily at each
monitoring visit.
Detail your plan for review here
The participants selected for monitoring and the extent of record review at each visit will be based on
the progress of enrollment, as well as any concerns that may emerge about the safety of human
participants, the integrity of study data or protocol compliance.
The following participant data will be source data verified for the indicated percentage of
participants enrolled in the trial and all incidences reported since the last monitoring visit:
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100% of consent or re-consent documents
100% of eligibility criteria
100% of SAEs
100% of drug accountability records for participants dosed
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
X% of participant CRFs
Any updates and/or revisions to the following study documents since the last monitoring visit will
also be reviewed:
 Training documentation/records and Task Delegation Log updates
 Regulatory documentation including Health Canada approval/amendments
The following activities may be conducted at each monitoring visit:
{Below is sample text to be customized based on study specific need.}
a) Trial Master File
o Ensure that essential document files are complete and current.
b) Investigator and Site Personnel Responsibilities
o Ensure that the Task Delegation Log is complete and signed.
o Verify that the QI and site personnel are adhering to the protocol and conducting the
study according to regulatory requirements, SOPs and ICH-GCP.
o Verify that study activities are being performed by the QI or have been delegated to
personnel qualified by appropriate education and training.
o Provide and document any necessary training for the QI and site personnel, such as
training on GCP, SOPs, protocol, Part C Division 5 of the Food and Drug regulations.
c) Informed consent form review - All subjects. Verify the following:
o Original signed consent (not copy version) present on site; all pages present
o The correct REB approved version of the consent document was signed and dated
o Consent was obtained prior to initiating any study procedures
o All appropriate signatures and dates were obtained prior to initiating any study
procedures
o Re-consenting with updated consent forms (if applicable and as directed by REB)
completed in a timely manner (ie. next visit at the latest)
o Copy of signed consent form provided to participant(s)
o Local privacy requirements followed
o Source documentation includes a description of the consent process
d) CRF Review / Source Documentation Verification. Verify the following:
o Accurate, complete, and current source documentation is maintained.
o Participants’ eligibility reviewed and signed off by QI/Sub-I.
o All procedures outlined in the protocol were completed.
o Missed visits, clinical procedures, and/or tests are recorded appropriately and reported
to the REB (if applicable) as protocol deviations, as defined by REB policy
o QI/Sub-I assessed all abnormal lab values for clinical significance or as outlined in
protocol.
o All participant discontinuations and/or withdrawals recorded appropriately in source
documentation.
o AEs, SAEs, concomitant medications and protocol deviations documented and reported
according to the protocol.
o All withdrawals and dropouts of enrolled subjects are recorded in the source
documentation and on the CRF.
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o
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o
o
o
The QI has reviewed, signed, and dated all required CRF pages in a timely manner
<specify for paper based studies, ink signature, or electronically signed all necessary
electronic Case Report Forms (eCRF) pages (for Electronic Data Capture (EDC) systems)>.
Data entries in the CRF pages coincide with the source documentation, and note any
errors, omissions, or discrepancies by issuing queries <insert form or system as
appropriate (e.g., on Data Correction Forms (DCF); within the EDC system), and revise
other bullets/text accordingly.>
Work with site staff to resolve queries while on-site and request the resolution of any
remaining queries that cannot be resolved during the visit.
Provide the site staff with copies of DCFs.
Verify that previously outstanding data queries have been resolved, signed, <ink
signature for paper studies, remove if EDC> and dated by the QI or designee.
e) Adverse Events, and Serious Adverse Events
o Verify all newly reported AEs and SAEs against source documentation.
o Follow up on previously reported AEs and SAEs.
o Confirm that all AEs and SAEs have been reported to the REB and Health Canada as
required.
o Identify any unreported AEs and SAEs in source documentation.
o Review AE and SAE reporting procedures, as necessary.
f)
Laboratory and Specimen Management
o Assess maintenance of research specimen logs and associated documentation.
o Review handling of laboratory specimens.
o Review specimen storage conditions and maintenance of temperature logs.
o Ensure organization and storage of specimens in a secure location.
o Ensure appropriate specimen labeling.
g) Protocol Specific Procedures / Investigations
o Ensure protocol mandated lab test results are recorded and reviewed* by QI or qualified
medical delegate.
o Ensure protocol mandated radiology test results are recorded and reviewed* by QI or
qualified medical delegate.
o Ensure all other protocol mandated test results are recorded and reviewed* by QI or
qualified medical delegate (if applicable).
* as evidenced by documented medical oversight (signature and date)
h) Investigational Product Treatment / Administration
o Ensure the correct dose as outlined in the protocol was administered.
o Ensure any dose modifications as outlined in the protocol were administered.
o Ensure compliance is recorded in source documentation.
i)
Investigational Product Accountability / Pharmacy Documentation
o Confirm that investigational product is stored at the correct temperature in a secure
storage area.
o Review temperature logs to confirm stability of storage/shipping conditions.
o Confirm that investigational product is being dispensed according to protocol.
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o
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j)
Confirm that product accountability records are accurate, current, and reconciled.
Ensure no discrepancies exist between drug accountability log and participant data on
CRF.
Ensure drug accountability log documentation is completed in chronological order in a
timely fashion
Ensure all transactions are documented on drug accountability log
Ensure the balance on the drug accountability log matches the inventory balance
Ensure all shipment receipts are retained
Ensure Certificate of Analysis (or other acceptable documentation) is on file for each
batch/lot received (Sponsor only)
Ensure all product orders are retained
Ensure product is returned/destroyed as mandated by protocol
Ensure no products is returned/destroyed prior to authorization to proceed
Ensure product return/destruction documents are retained
Protocol Deviations
o Verify that all protocol deviations are documented appropriately in each participant’s
research record and on the appropriate protocol deviation form.
o Ensure that the site has reported all protocol deviations to the REB, as defined by REB
policy and/or SOPs.
o Address any protocol deviations with site personnel during the monitoring visit and
identify ways to prevent a recurrence of similar issues.
k) General
o Confirm all data is verifiable against source documentation.
o Confirm no transcription errors have been made.
o Ensure corrections are lined out, dated & initialed (no erasures or “whiteouts”).
l)
Visit Conclusion
At the conclusion of the visit, the monitor will meet with the QI and site research staff to review
visit findings and answer questions. The monitor will discuss the following topics at a minimum:
o Enrollment progress.
o Consent process and documentation.
o Study conduct and documentation of study activities.
o AEs and SAEs experienced by study participants.
o Deviations.
o Scheduling of the next Monitoring Visit.
m) Reporting for Identified Issues
During the monitoring process, the monitor will assess study files and documentation against ICHGCP, regulatory requirements, protocol, SOPs and any study-specific SOPs. All observations noted
during the monitoring visit will appear in the monitoring report and associated follow-up letter. The
monitor will address deficiencies to the appropriate study team member in order to implement
corrective actions or to recommend follow-up procedures. Opportunities for the monitor to meet
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with the QI or study coordinator will be made periodically during the visit. These meetings will allow
study staff to provide clarification of findings, ask questions, and work with the monitor to address
certain issues at the time of the monitoring visit.
5.4
Close-Out Procedures
The monitor will conduct close-out procedures when appropriate. During close-out visit, the monitor
will perform the following:
o Ensure the completion of outstanding case report forms and queries.
o Ensure all previous monitoring corrections have been addressed.
o Ensure the return or destruction of the IP (if applicable).
o Collect outstanding participant data forms and study forms (ex. screening and
monitoring logs).
o Perform a final review of the study file documents.
o Review the plans and location for record retention.
o Ensure all SAEs have been reported appropriately.
o Ensure the QI has notified the local REB of the site closure.
o Ensure Health Canada has been notified of study closure (within 15 days of closing).
The monitor will prepare the final monitoring report and send it to the site for their records and
to Quality Assurance & Education, HRPP at SRI. The site will address all monitoring observations
(including observations from previous monitoring reports) prior to final study closeout.
6.0
Non-compliance
Non-compliant conduct of the study will be documented in a monitoring report and forwarded to the
Global Principal Investigator, Sponsor delegate and any applicable stakeholders. It is the responsibility
of each Qualified Investigator to address all observations outlined in the monitoring report and ensure
appropriate and compliant procedures are implemented in a timely manner.
7.0
Monitoring Report
The report will include the following:
a.
b.
c.
d.
e.
f.
Date
Monitor name
Qualified Investigator name
Study status overview
Summary of reviewed documents
Observations detailing:
i. Findings
ii. Recommended corrective and/or preventative actions (CAPAs)
iii. Action Items/Follow up plan
iv. Comments
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The study monitor will generate monitoring reports after the completion of every monitoring event.
The study monitor will communicate findings to the site in a timely manner. The site will respond to any
queries, observations and/or comments listed in the monitoring report. The QI will sign, date and return
a signed copy of the monitoring report to the monitor. The monitored site will keep a signed monitoring
report in the site files for their records and will use the report as a reference in any subsequent
monitoring visits.
The trial-coordinating centre will review reports prior to sending a copy of the report to the monitored
site. The trial-coordinating centre will retain the original report.
References:
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International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. Section
5.18 http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ich/efficac/e6eng.php
Health Canada Therapeutic Products Directorate Food and Drug Regulations for Clinical Studies.
Division 5. Canada Gazette Part II, Vol. 135, No. 13, June 7,2001
http://lawhttp://laws-lois.justice.gc.ca/eng/regulations/C.R.C.,_c._870/slois.justice.gc.ca/eng/regulations/C.R.C.%2C_c._870/page-276.html#h-253
Guidance for Industry- Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UC
M269919.pdf
Adapted, in part, from Ottawa Hospital Research Institute’s monitoring plan
Reference Guidelines
Use these documents to customize your monitoring plan
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Health Canada Natural Health Products Regulations. Canada Gazette Vol. 137 No. 13, June 18th 2003
http://archive.is/O7Fii
Health Canada Medical Device Regulations http://www.hc-sc.gc.ca/dhp-mps/md-im/index-eng.php
Tri-Council Policy Statement 2 – Ethical Conduct for Research Involving Humans
http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/Default/
Personal Health Information Protection Act, 2004.
http://www.e-laws.gov.on.ca/html/statutes/english/elaws_statutes_04p03_e.htm
Personal Information Protection and Electronic Documents Act. http://lawslois.justice.gc.ca/eng/acts/P-8.6/index.html
Internal Monitoring – SoCRA SOURCE. November 2011 – 35. Clinical Investigation of medical devices
for human subjects – ISO 14155 http://www.iso.org/iso/catalogue_detail?csnumber=45557
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