The document defines key terms related to clinical trial monitoring such as monitoring, monitoring visits, and monitoring reports. It describes the purpose of monitoring is to protect subjects, ensure accurate data, and ensure compliance. It discusses selecting qualified monitors and different types of monitoring visits including site evaluation, initiation, routine monitoring, and close-out visits. The key responsibilities of monitors during visits are also summarized.

1. Monitoring
Visits
Jobin Kunjumon
Vilapurathu

2. Definition
Monitoring
The act of overseeing the progress of a clinical trial, and
of ensuring that it is conducted, recorded, and reported in
accordance with the protocol, SOPs, GCP, & the applicable
regulatory requirements.
Monitoring Report
A written report from the monitor to the sponsor after
each site visit and other trial-related communication
according to the sponsor’s SOPs.

3. Purpose
 The rights & well being of the human subjects are protected .
 The reported trial data are accurate ,complete and verifiable
from source documents.
 The conduct of the trial is in compliance with the currently
approved protocol or amendments, with GCP & with
applicable regulatory requirements.

4. Frequency
Frequency of monitoring visits is not defined by ICH or FDA
regulations
 ICH states that “the sponsor should ensure trials are
adequately monitored before, during and after the study”.
 The frequency of monitoring depends on
◦ The complexity of the study
◦ Rate of enrollment
◦ GCP compliance issues

5. Selection & Qualification of monitors
 Should be appointed by the sponsor.
 Should be appropriately trained & should have
scientific/clinical knowledge.
 Qualification should be documented.
 Should be thoroughly familiar with the IP, protocol, ICF, & any
other written information to be provided to subjects, the
SOPs, GCP & applicable regulatory requirements.

6. Types
The most common types of site visits for industry-sponsored
studies:
◦ Site Evaluation/Qualification Visit
◦ Site Initiation Visit
◦ Site Monitoring Visit
◦ Site Close-Out Visit

7. Site Evaluation Visit
ICH Guidelines nor FDA regulations specifically require a Site
Evaluation Visit.
ICH does require a pre-trial monitoring report as part of the
“Essential Documents” and states that there is a need for on-site
monitoring “before, during and after” a trial.
FDA “Guidelines for the Monitoring of Clinical Investigations”
does recommend that a monitor visit the site of the clinical
investigation prior to the initiation of the trial.

8. Site Evaluation Visit
 Investigator’s Qualifications:
1. Up-to-date CV
2. Specialty
3. Previous experience in conducting trial.
 Adequate Resources:
1.Retrospective data
2.Sufficient time
3.Adequate number of qualified staff

9. Site Evaluation Visit
 Adequate facilities:
1.Exam rooms
2.Pharmacy/Study drug storage area
3.Laboratory or specimen processing area
4.Special testing areas ( x-rays, CT scans, endoscopy, etc.)
5.Record keeping facilities

10. Site Evaluation Visit
 Protocol review/discussion
◦ Study objectives
◦ Inclusion/exclusion criteria
 Are there barriers to enrollment at your site?
◦ Study Procedures/Tests
 Can you perform all the procedures/tests required
for the study?
◦ Schedule of Assessments
 Special considerations such as weekend/24 hour
coverage, etc.
◦ Are there any competing trials?

11. Site Initiation Visit
 The purpose of the SIV is to assists the site in its preparation
to enroll its first subject & should take place after all required
supplies are at the site and just before subject recruitment
begins.
 ICH GCP does require a Trial Initiation Monitoring report as
part of the “Essential Documents” and the report should be in
both the sponsor and site file.
 FDA Guidelines recommend that a monitoring visit should
take place “shortly” after the site has enrolled its first few
subjects if an SIV was not conducted.

12. Site Monitoring Visit
ICH 5.1.8.4, Monitor’s Responsibilities
 Acting as the main line of communication between the
sponsor and the investigator.
 Verifying that the investigator has adequate qualifications
and resources throughout the study.
 Verifying that the investigational product is stored, dispensed
and returned properly and that only eligible subjects receive
it at the protocol specified dose.
 Verifying that the investigator follows the approved
protocol/amendments.

13. Site Monitoring Visit
 Verifying that written informed consent was obtained before
each subject’s participation in the trial.
 Ensuring that the investigator receives the current
Investigator’s Brochure and safety updates.
 Ensuring that the investigator and the investigator’s staff are
adequately informed about the trial.
 Verifying that the investigator is enrolling only eligible
subjects.

14. Site Monitoring Visit
 Verifying that the investigator and the investigator’s trial staff
are performing the specified trial functions, in accordance
with the protocol, and have not delegated these functions to
unauthorized staff.
 Reporting the subject recruitment rate.
 Verifying that source documents and other trial records are
accurate, complete and up-to-date.

15. Site Monitoring Visit
 Informing the investigator of any CRF entry error, omission or
illegibility. The monitor should ensure that appropriate
corrections, additions or deletions are made, dated, explained
(if necessary) and initialed by the investigator or a trial staff
member that has been authorized to make CRF changes for
the investigator. This authorization should be documented.
 Determining whether the investigator is maintaining the
essential documents.

16. Site Monitoring Visit
 Determining whether all adverse events are appropriately
reported within the time periods required by GCP, the
protocol, the IRB, the sponsor and the applicable regulatory
authorities.
 Communicating deviations from the protocol, SOPs and GCP
to the investigator and taking appropriate action designed to
prevent recurrence of the deviations.

17. Monitoring Report
Monitor submits to the sponsor after each trial site visit:
o Written report.
o Should include date, site, name of the monitor, investigator or
other individuals contacted.
o Summary of what the monitor reviewed & the monitor’s
statements concerning significant findings/facts, deviations &
deficiencies, conclusions, actions taken or to be taken
&/actions recommended to secure compliance.
o Review & follow-up of the report with the sponsor should be
documented by sponsor’s designated representative.

18. Site Close-Out Visit
There are no clear ICH or FDA regulations regarding the close-
out visit.
ICH GCP requires a close-out monitoring report as an Essential
Document.
In general, three activities are required to “officially” close-out a
site.
◦ The sponsor conducts a close-out visit and signs the
monitoring log.
◦ The investigator submits a final report to the IRB stating
that the site is closed.
◦ The sponsor sends the investigator a letter stating that the
site is closed.

19. Site Close-Out Visit
Close-Out Visit Activities
◦ Final data review/collection of all outstanding data
◦ Return or destruction of all study drug
◦ Final review of Regulatory Binder
◦ Verification that all biological samples have been submitted

20. Site Close-Out Visit
◦ Return or destruction of all unused study forms/CRFs
◦ Review and collection of Delegation of Authority forms
◦ Collection of IRB closure report/letter