Monitoring Plan and Basic Monitoring Visits: Everything that a CRA

Needs to Know

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

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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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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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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Traditional

Monitoring

Risk-

Based

Monitoring

4 to 6 weeks

6 to 12 weeks

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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. 9

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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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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 administeringIP receiving

IP accountabilityIP storage

Return and destruction of the IP

Subject dosing compliance

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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

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

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

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

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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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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CONCLUSIONAll 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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