2. Act of overseeing the progress of a clinical trial
Ensures that the study is conducted, recorder and
reported in accordance with:
Protocol
GCP
Applicable regulatory requirements
SOP
3.
4. Purpose
To verify that:
The rights of subjects are being protected
Conduct of trial is in compliance with GCP, currently
approved protocol/amendments
The data is complete, verifiable
5. FREQUENCY OF MONITORING
VISITS
The sponsor should ensure that the trials are adequately
monitored
Number of factors determine the frequency of monitoring
visits:
Complexity of the protocol
Experience of the investigator/staff
Number of study subjects enrolled at the site
Rate of enrolment
Site performance
All sites should be visited soon after the first subjects are
enrolled to be sure the site is following protocol procedures
6. Catching and solving problems early will save a lot of
extra work as the study progresses.
The more subjects a site has, the more frequently the
CRA will have to visit
The faster a site enrols and the more data generated, the
more frequently the site will need monitoring
The CRA should visit a site regularly even though
enrollment may be slow
The frequency and duration of monitoring visits will vary
from site to site depending on the experience of the
investigator and staff
7. In some instances, sponsor SOPs dictate the frequency
of monitoring visits
The frequency of monitoring visits may change as the
study progresses
Subject visits may spread out over the course of long-
term studies and require less review
8. Another factor that has an impact on CRA visits
frequency is the number and location of sites for
which they have monitoring responsibility
With the complexity of protocols, regulatory
requirements, they will need to spend a day or more
at the sites
A good CRA should be able to monitor 5-10 sites
Number will change depending on complexity of
study, site, CRA experience
9. Selection, qualification of monitors
Monitors are appointed by the sponsor
Should be appropriately trained
Have scientific/ clinical knowledge
10. Monitoring visits
PRE-TRIAL: ensure feasibility at the site and interest
of investigator
SIV: ensures that the study team understands GCP
and protocol requirements
ROUTINE MONITORING VISIT: make sure study is
conducted according to protocol
SITE CLOSE OUT VISIT: investigator files are
archived properly and collect unused material,
documents
11. Tasks
Verify resources remain adequate throughout trial
period
investigator receives the current Investigator's
Brochure, documents, and all trial supplies needed for
proper conduct of study
the receipt, use, and return of the investigational
product(s) are controlled and documented adequately.
…
the disposition of unused investigational
product(s)complies with applicable regulatory
requirement(s)
12. That the investigator is enrolling only eligible subjects
that written informed consent was obtained before each
subject's participation in the trial
Verify that source documents and other trial records are
accurate, complete
Verify CRFs match with the corresponding source
documents
13. Verify CRFs are completed only by authorised persons
Corrections made to CRFs are signed, dated and backed
by source documents
Report the subject recruitment rate
…
Trial progress
Problems/ needs at site
14. Monitoring activity
CRA should have a plan for what will be monitored at
each site visit
CRA should send the monitoring visit confirmation
report and a follow up report
This report is a standard document that CRA will use
for all monitoring visits
Serves as a checklist for the CRA and as a
documentation of the visit
15. Important to know what you need to monitor at each
site
How much time and attention to be given to each
activity
Helps the CRA to pinpoint areas where problems are
most likely to arise
16. Aspects of monitoring
According to the U.S. Food and Drug Administration's
Center of Drug Evaluation and Research, the top five
deficiency categories for site inspections caught by clinical
monitors as reported in the 2001 Report to the Nation[4] are:
Failure to follow investigation protocol (the procedures and
treatment subjects must undergo, as well as the schedule of
assessments)
Failure to keep adequate and accurate records
Problems with the informed consent form
Failure to report adverse events
Failure to account for the disposition of study drugs
17. Therefore, the primary goal of clinical trial monitoring
is to observe each trial site to ensure that the
standardized operation procedures for the trial are
being followed, reporting and managing any
deviations from the investigation plan as they occur.
18. The overall monitoring plan should remain fairly
consistent, but the strategy for individual sites may
change considerably during the course of the study
depending on study conditions and site performance.