Monitoring Visits: An Overview of the Different Types of CRA Visits

CRA Training and Certification Renewal Credits

Monitoring Visits: An Overview of the Different Types of CRA Visits

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Monitoring visits are an essential component of any clinical research project.  They help the sponsor and the Clinical Research Associate (CRA) confirm the integrity of the study data as well as ensuring the safety of the study subjects/participants.  During these visits the CRA will confirm if the study sites are following the protocol, ICH/GCP guidelines, regulatory requirements, and if the data collected is accurate and reliable.

In this article and episode of the "Let's Get Clinical" podcast, we will discuss the different types of monitoring visits that a CRA can perform during a clinical trial.

Pre-Study Visits (PSV) Explained:

Pre-Study Visits (PSVs) or Site Selection Visits (SSVs) are the first type of monitoring visit and are usually completed before the study begins. In addition to confirming the qualifications and experience of an investigator, a PSV/SSV is performed in order to assess the adequacy of a site (including assessment of facilities and equipment), potential patient population, and the training/experience/availability of site staff as well.

Site Initiation Visits (SIV) Explained:

After a site is selected, the next type of monitoring visit that a CRA will perform are Site Initiation Visits (SIVs). The purpose of this visit is for the CRA to thoroughly train the site regarding every aspect of the study, including the protocol, investigator responsibilities, safety reporting, IP, vendors used, all procedures, CRF completion, monitoring, etc.  Another purpose of the SIV is to confirm if the site is ready for activation and if able to start enrolling subjects (does site staff have access to study systems, all supplies received, etc).

Interim Monitoring Visits (IMV) Explained:

Interim Monitoring Visits (IMVs) are conducted during the course of the study.  Per GCPs, the purpose of monitoring visits is to ensure that the rights and well-being of human subjects are protected, and that study data is accurate, complete, and verifiable from source documentation. Monitoring visits are also performed to ensure that the study is being conducted in compliance with the protocol, GCPs, and regulatory requirements.

Close-Out Visits (COV) Explained:

The final type of monitoring visit is a Close-Out Visit (COV).  The purpose of a COV, is like the name, ensuring the site is ready for 'closure'. The monitor will perform final reconciliation of study documents, study supplies, and ensure that the PI is aware of all regulatory obligations after closure, etc.

Each monitoring visit is an integral part of the clinical research process.

In conclusion, the different types of monitoring visits, PSVs, SIVs, IMVs, and COVs, are designed to ensure that the study is being conducted in a way that the subjects are safe and the data is valid.  The CRA must ensure that sites are performing the study in compliance with the protocol, ICH/GCPs, and regulatory requirements as well as confirming that all study data is complete, accurate, and verifiable.  

A well-executed Clinical Monitoring Plan (CMP), with appropriate visits and critical variables to be reviewed, ultimately leads to a successful and reliable clinical study.

 Listen to the Podcast Episode

Enjoy the transcript from today's episode!

Hi, and welcome to Let's Get Clinical. Tips from the CRA Helper. Here is your host, Elizabeth Waddell. Hi, Elizabeth here, and welcome to Episode 20, where I will address questions regarding monitoring visits.

A little bit of a different format today, where I will start with some questions and jump in with the answers.

Let's see.

Understanding Different Types of Monitoring Visits

What are the most common monitoring visits performed, and what is your favorite type of monitoring visit? The best way to answer these would be to run through the types of visits first, especially for those that are research naive and if this is new to you. Now remember, I'm only going to touch on the type of visits as my new course, CRA Foundation Training goes into detail regarding this, reviewing every visit type, why they are required and what specifically is to be performed at each.

But to answer these questions, I will need to touch on the types of visits and their purpose.

Pre-Study Visits (PSV) Explained

To start off, in order for a sponsor or CRO to confirm if a site will be used for a study or not, a CRA will need to perform what's called a pre study visit, a PSV. This is also known as a site selection visit.

depending on what company you work for. And this visit is performed in order to determine if an investigator has the experience, the qualifications, the resources, the staff, the time, the facilities to properly conduct the study as well as having the appropriate patient population. Will they have the required subjects needed for the study?

Now this visit consists of a tour and lots of things to confirm. It's a lot like an interview. again, I will review all of the details, all of the information that's to be confirmed in my course, but I at least wanted to give an overview of the purpose of this visit. And then, after the monitor reports all the findings from the visit and if the site would be recommended or not, the sites must actually be approved or selected by the sponsor in order to participate in the clinical trial.

Site Initiation Visits (SIV) Explained

Now, once all the sites have been selected and they get to the SIV phase of the trial, the CRA will be notified when to schedule a site initiation visit, an SIV with the site. Now, these typically occur after the site receives that initial IRB approval and the contract has been executed. Sometimes there may be exceptions to this, and sometimes they're not, as CRAs sometimes are all packed up ready to go out the door heading to the airport and they may receive a call that the visit needs to be rescheduled because maybe there's a hiccup with the IRB approval or maybe an issue with the contract and then they have to reschedule that SIV.

So sometimes that happens, but the visit is like the name to initiate or to begin. So this visit will set a standard as you are training the site on all the intricacies of the study from the protocol, investigator responsibilities, safety reporting, IP. The vendors that are going to be used all study procedures, CRF completion and monitoring of the study.

Now another purpose though of the SIV is to confirm if the site is ready for activation and ready to start enrolling subjects. Now depending on the study as well, the CRA may also perform. Initial review of the regulatory binder, study drug, and confirming study supplies received and they also want to make sure that the site is ready for activation in order to enroll subjects So we need to also confirm does that site staff have access to IVRS, the study systems, EDC?  Making sure they're ready for activation.

Routine Monitoring Visits (RMV) Explained

And next are the routine monitoring visits, RMVs, or some companies may call these interim monitoring visits, IMVs, again, just depends on the company, but your clinical monitoring plan, your CMP will specify when that first RMV is to occur. So for example, once you're notified of that first subject screened, it may say that you have to perform that first monitoring visit within 10 days.

but prior to randomization. So this first visit is usually a tight window, which is understandable as this is the site's first subject and you want to ensure they are truly eligible meeting all of the inclusion criteria and no exclusion criteria. So it's very important that these visits are on time and per the CMP.

And there have been times where upon review, I've been out there for that first monitoring visit, and I've realized that subject is not truly eligible, and then they had to be screen failed. So that is why it is very understandable of that tight turnaround time where you have to get out there and monitor that first subject.

Now all the subsequent visits will be specified in the CMP as well. So for example, after that first monitoring visit, then maybe every subsequent visit thereafter may have to be performed say every six to eight weeks. And these are called monitoring visit intervals. Now, per GCPs, the purpose of monitoring visits is to ensure the rights and well being of human subjects are protected, remember subject safety, data integrity is the most important, and that study data is accurate, complete, and verifiable from source documents.

And we also must verify that the study is being conducted. In compliance with the protocol, GCPs, and regulatory requirements. So there are so many tasks that CRAs must perform at these visits in order to confirm this information, which again, I review in detail during CRA Foundation training. These visits include so much from consent and HIPAA review, source review, CRF review, which includes SDR, SDV, review of study drug, the reg binder, study supplies, continued assessment of the adequacy of the site, and so much more.

And your CMP will specify all that is to be performed as well.

Closeout Visits (COV) Explained

Now, lastly, the closeout visits, the COVs. These typically occur when study conduct is no longer being conducted and the database is locked. However, there are times when a site may be closed due to no subject enrollment, for example. But the purpose of this one is like the name.

You want to ensure the site is ready for closure. So the CRA will perform that final reconciliation of study documents and ensure that the PI is aware of regulatory obligations after closure and more. In a nutshell, each site will have one PSV, one SIV, and one COV, but the RMV, those routine monitoring visits can go in the double digits, depending on the length of the study and the monitoring intervals.

So for example, I have my site that has their PSV, then they'll have their SIV when they're initiated. And then for that maintenance phase of the trial, I'll be performing all these routine monitoring visits. And again, I could perform, for example, say 15 RMVs for that particular site, for that particular study.

And then. At the end, I'll perform one COV to close them.

Comparing Different Types of Visits

So to answer the question, the most visits I have conducted are those routine monitoring visits because you perform so many more for each site during the trial.

Personal Preferences and Experiences with Different Visits

Now my favorite would have to be And this is hard because I like different things about all of them, but I would first probably pick PSVs, the pre study visits, because with my experience with CNS studies, most sites I would visit were private practice or research facilities.

So most of my pre study visits would average about three hours. So I would be prepared with my checklist. I knew everything that I needed to do. every area I needed to visit and I would just go to the site and I would knock the visit out. So again, about three hours on average. So when I compare that with a routine monitoring visit, that could be one full day or multiple days, depending on your CMP design.

And there's so much to review and so little time when you compare these two, I would definitely probably pick a PSV. And I like SIVs too, because remember, site initiation visits, that involves training, and you know I love to train, so I do like SIVs as well. And those on average for my CNS studies could be anywhere from four to six hours.

So again, it wasn't a full day, again, involved lots of training, which I love to do, so I do love SIVs as well. And then when it comes to COVs, those closeout visits. If you have a low enrolling site, for example, and you are so caught up, including all that ISF and TMF reconciliation, like you are so far ahead.

If you have to return study drug, you have all that completed already. Then you go to conduct your COV, your closeout visit. Then because you're so far ahead, this prepares you when it comes time to your closeout visit. So when you get to your COV, it goes a whole lot smoother, so much easier. And sometimes those are even shorter because you prepared so much in advance. So sometimes these aren't as bad either.

And there are things I like about RMVs too. I like monitoring, but when you're traveling like 14 years nonstop, I do tend to like the shorter visits. And it was funny with PSVs and SIVs. I used to think, man, I wish they had CRAs dedicated to initiating sites, or maybe they would be with study startup and perform PSVs, pre study visits, site selection visits, for studies.

Job Opportunities in Clinical Research

And I actually have seen some job opportunities at some companies where they do have CRAs that are dedicated to performing initiation visits. So I thought that was so cool.

Conclusion and Course Promotion

So wow, I have been going on and on and I've only gotten through two questions for the time I have allotted on this episode. So I do hope that these examples and running through the types of visits have been helpful.

And if you like what you hear, hit subscribe and also. Like I mentioned, my new course CRA Foundation Training will cover all the types of visits in detail, the purposes for each and the monitoring tasks required at each. And I also have checklist templates for each type of visit for you to use, and will teach you step by step how to perform the different monitoring procedures.

So check it out on my website. You can learn more at thecrahelper. com. I pray you guys are safe out there and I look forward to our time together during the next episode. Until next time.