The document discusses the key components of a clinical trial monitoring plan for a clinical research associate (CRA). It outlines the CRA assignments and guidelines, the monitoring visit timeline, and types of visits including pre-study visits, site initiation visits, interim monitoring visits, close-out visits, and pre-audit visits. It also covers traditional versus risk-based monitoring and the knowledge required about investigational products, interactive response systems, problems/adverse events, and shipment/inventory. The goal is to explain everything a CRA needs to know to properly conduct monitoring according to regulations and guidelines.

1. Monitoring Plan and Basic Monitoring Visits:
Everything that a CRA
Needs to Know

2. Introduction
A monitor in a clinical trial is also called a CRA - clinical research
associate. This person is a professional who’s responsible for
monitoring the clinical trial and making sure that everything is
according to rules, regulations, and good clinical practice.
Whether you already are a CRA or you’re trying to become one, the most
important thing you should be aware of is the monitoring plan. You, as a
CRA or a future CRA, should know what a monitoring plan is, what it
serves for, and what it consists of. The second most important
information for you are the monitoring visits. Below, we’ll explain all the
components of a monitoring plan, as well as which are the most basic
and important monitoring visits.
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Components of a Monitoring Plan
Part I

4. CRA Assignments
The first thing that happens before the study starts
is the CRA site assignment.
That means that you will be assigned the sites
which you’re going to monitor, and then you’ll be
trained on the protocol for every study.
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5. CRA Guidelines
Another thing that happens before the beginning of
the study is the establishment of guidelines for the
CRA.
These guidelines will entail: your internal
communication chain, the person you should
report to (project manager or team leader), your
communication with the site, your communication
with the sponsor, etc. These are the things that will
be stated in the guidelines even before the study
starts.
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6. Monitor Visit Timeline
The timeline that you’ll be given will contain
information such as the frequency of site visits,
which site to visit when, etc. Usually, in traditional
monitoring, you will visit sites every 4 to 6 weeks,
while in risk-based monitoring the visits will be on
every 6 to 12 weeks. In this timeline, you will also
enter any schedule changes that might occur
throughout the duration of each study. Such
changes in the schedule should always be
reported to the CRO as well as the site. The
communication method of scheduling and
notifying all parties should also be stated and
explained in the timeline.
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Types of Monitor Visits
Pre-Study
Visits (PSVs)
Site
Initiation
Visits (for
your sites)
Site Selection
Visits
Interim
Monitoring
Visits
(Routine
Monitoring
Visits)
Close-Out
Visit
Pre-Audit
Visits
Monitor Visit
Report
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Traditional Monitoring vs Risk-Based Monitoring
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Traditional monitoring is a term
used to describe monitoring based
only on source data verification
(checking the validity of all reported
data by comparing it to originals).
However, it’s known that this way
of monitoring might require
unnecessary resources that could
be better spent elsewhere. For this
reason, the FDA has proposed a
new method of monitoring known
as risk-based monitoring.
Risk-based monitoring entails the
allocation of resources based on risk
profiles and areas of need instead of
spending these resources everywhere
equally. The aim of this monitoring is to
increase the efficiency without causing any
harm to data quality. With risk-based
monitoring, CRAs will be able to focus
toward the more risky areas of different
sites and work more strategically.
Nowadays, more and more people prefer
and use this type of monitoring over the
traditional one. One of the most important
features of risk-based monitoring is the
individual profile for each site.

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Problems and Adverse Events
You, as a CRA, will be given some
sort of a guideline that will help you
and show you how to deal with any
problems that might arise
throughout the study, as well as
how to react and report when any
adverse events occur. Knowing how
and when to react is important for
the safety of patients as well as the
good performance of the site. The
CRA is the person who’s basically
guiding the site and making sure
that it acts in compliance.
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IVRS/IWRS Knowledge
IVRS stands for Interactive Voice Response
System and IWRS for Interactive Web
Response System. These systems are used
to simplify the management of
randomizing, enrolling, and dismissing
subjects, as well as to optimize the supply
and stock of IP (investigational products). As
a CRA who’s responsible for monitoring the
whole drug accountability and
randomization process, you should be
familiar with the way these systems work. In
this way, you’ll be able to better understand
and follow your monitoring tasks and act
when something isn’t done right.
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11. www.trialjoin.com Investigational Product (IP) Knowledge
Knowledge of the investigational product is also important for a CRA. You will be presented with a plan for
each of the areas below which you’ll have to follow and respect throughout the whole duration of the
study (until the end of the close-out visit).
IP preparing and
administering
IP receiving
IP accountabilityIP storage
Return and destruction of
the IP
Subject dosing
compliance
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12. Orders, shipment, and inventory
In this area, you’ll have to monitor and make sure
that the site takes proper actions regarding orders,
shipment, and inventory storage.
An example of such things are equipment, lab kits,
properly regulated storage areas, etc.
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Basic Monitoring Visits
in Clinical Research
Part II

14. Site Selection Visitwww.trialjoin.com
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In practice, the site that’s interested in
conducting a certain study will first fill
out a Feasibility Survey which the
sponsor will review. Next, if the sponsor
considers you to be a good option for
their study (based on the feasibility
survey), they’ll send a CRA to come for a
site selection visit. On this visit, it’s the
CRA’s task to confirm that the site
actually exists and that everything that
they’ve stated in their feasibility survey
matches the real situation.
A site selection visit means that a CRA goes to
visit a certain site before it can be awarded a
study.
Apart from this, the CRA will
also make sure that the site has
enough experience to conduct
the study and that they’re able
to enroll the required number
of patients. This type of visits is
normally pretty straightforward
and easy for CRAs because they
don’t require a lot of in-depth
knowledge. However, the CRA
still has to be familiar with the
study requirements in order to
be a good judge in this
scenario.
CRA Knowledge Level

15. Site Initiation Visitwww.trialjoin.com
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This visit happens after the site has been
selected, the terms and budget have
been negotiated, and all the documents
have been signed. Basically, the site
cannot start screening patients until the
site initiation visit happens. Contrary to
the first type, these visits do require that
the CRA has more knowledge and
understands the protocol in-depth. The
site initiation visit entails that the CRA
confirms that all the regulatory
documents are accurate and present, all
the IRB reviews are in place, the contract
and budget are present, the non-
disclosure agreement is signed and
present, and basically that all other
important documents are accurate.
Apart from all of these things, the
CRA will also have to make sure that
the coordinator and the PI are both
up-to-date with everything and that
they’re properly trained and have a
good understanding of the protocol.
Next, the CRA will have to make sure
that the site has all the login details
for the EDC system as well as all the
other systems that the site uses,
make sure that all the laboratory kits
are present and accounted for, etc.
These are some of the basic tasks of
a CRA during a site initiation visit,
although, in practice, there are many
more details that the CRA will be
responsible for.
CRA Knowledge Level

16. Regular Monitoring Visitswww.trialjoin.com
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These are the visits that require the most in terms of CRA experience and
knowledge of the protocol. However, almost all monitors (CRAs) are only
given one study at a time - which means only one protocol to learn and
understand. Even though a CRA could be given multiple sites to handle, most
of them will be doing the same study, which makes this job a bit easier.
Since we’ve started explaining about regular monitoring visits, CRAs should
know that there are two types of regular visits - traditional and risk-based. In
any case, every CRA will have a monitoring plan which will explain what type
of monitoring visits are required. Depending on the type of monitoring visits,
the CRA will know what he/she is supposed to do on these regular visits. So, if
it’s traditional monitoring, the CRA will have to do a complete source data
verification (checking if all the reported data matches the originals). However,
if it’s a risk-based monitoring, then the CRA will only focus on the areas which
the sponsor considers to be risky for that site and study.
CRA Knowledge Level

17. Site Close-Out Visitwww.trialjoin.com
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The close-out visit takes place when the study has already finished. A study can end for various reasons, either
because it has been successfully completed or the sponsor dropped the study or even when the sponsor dropped the
site because he/she decided that this particular site isn’t a good fit for their study. No matter what’s the case, the
close-out visit is always the same for the CRA, whose job would be to:
Ship the IP back
to the sponsor -
both used and
unused IP;
Make sure that the
lab kits are
destroyed;
Make sure that the
site has a plan and
an arrangement
for keeping all the
medical records;
Check if the site
has notified the
IRB that all the
research for that
site and study is
finished;
Check that all the
safety reports are
signed and filed
appropriately, as
well as all the other
documentation;
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18. Pre-Audit Visitwww.trialjoin.com
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The fifth and last type of visit we’re going to explain to
you is the pre-audit visit. As the name itself entails, the
pre-audit visit is when the monitor (CRA) comes at the
site to prepare it or make sure that it’s prepared for an
upcoming audit. This audit can be the FDA, the sponsor,
etc. In this case, the CRA will look for any protocol
deviations, check IP accountability, PI oversight, and
basically check all the documentation and make sure
that there aren’t any mistakes. In short, the CRA has to
make sure that everything is in perfect order, there
aren’t any mistakes, and that the site is completely
prepared for an audit.

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CONCLUSION
All of these things that we explained above are part of a monitoring plan. As we said before, CRAs will receive
guidelines and plans for each item above which they’ll use to properly conduct their monitoring visits. Even though
CRAs are monitors and they’re only there to supervise, they’ll have to be equipped with all this knowledge in order
to be able to point their sites to the right direction. A huge part of the monitoring plan are the monitoring visits. In
the second part of this short guide, we’ve given you all the details regarding each of these 5 monitoring visits.
Hopefully, we’ve managed to help all present and future CRAs out there to better understand their roles in clinical
research.
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