Selecting a Site for Your Clinical Trial

In this episode, we discuss how to select a site for a medical device clinical trial. 

Joining us for the conversation is Isabella Schmitt, MBA, RAC, the Vice President of Life Science Solutions at Proxima Clinical Research. Isabella brings a wealth of knowledge and experience in the intricacies of clinical study site selection, shedding light on the critical role it plays in MedTech product development.

In addition, we're joined by Samantha Pickett, an Associate Director at Proxima Clinical Research. Samantha dives deep into the key considerations for site selection, emphasizing the significance of patient demographics, regulatory compliance, and technological access.

This was a fun conversation as we discussed how to navigate the complexities of regulatory landscapes, explore collaboration strategies, share best practices, and draw insights from real-world case studies.

Listen now:

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Some of the highlights of this episode include:

• Why Site Selection Matters

  • In the realm of MedTech product development, site selection is the linchpin. It can make or break the trajectory of your innovation.

  • Selecting the right geographic location and clinical trial site sets the stage for successful outcomes and paves the way for future success.

• Key Considerations for Site Selection

  • Let's dig into the key considerations when selecting a site for your clinical study. Patient demographics, regulatory environment, and investigator expertise are vital factors.

  • Infrastructure, access to cutting-edge technology, and the patient population at the site are equally critical aspects to consider.

• Navigating Regulatory Landscape

  • Regulatory challenges can be formidable obstacles in the site selection process. We'll explore the complexities and implications these challenges can have.

  • Tune in to learn about strategies that can help you navigate these hurdles, ensuring compliance and successful site selection.

• Collaboration and Partnerships

  • Collaborating with research institutions, hospitals, and academic centers can be a game-changer. We'll discuss the numerous benefits this collaboration can bring to your site selection process.

  • Moreover, we'll provide insights into strategies for establishing fruitful partnerships that enhance your site selection efforts.

• Best Practices and Case Studies:

  • Let's delve into real-world examples from the MedTech industry. We'll share success stories and case studies that illuminate the art and science of site selection.

  • By extracting actionable insights and best practices from these examples, we aim to empower you in your own site selection endeavors.

Links:

• Samantha Pickett
• Isabella Schmidt
• GG Academy
• Greenlight Guru
• Etienne Nichols LinkedIn

Memorable quote:

"Your aim should be to ensure everything aligns with expectations. The IRB's primary focus is patient protection, ensuring they comprehend the trial's details, risks, and benefits while safeguarding their privacy." - Samantha Pickett

Transcript:

Etienne Nichols: Hey everyone. Welcome back to the Global Medical Advice Podcast. My name is Etien Nichols. I am the host of today's podcast, and I hope I got my name right because this is not take one.

That's okay. We hit me up sometime if you want to want to talk about take one. Today with me is Samantha Pickett, who is the Associate director at Clin Proxima Clinical Research as well to help support the conversation is Isabella Schmidt, who is the Vice President of Life Science Solutions at Proxima Clin Research.

Today we're going to be talking a little bit about site selection and diversity planning for your clinical investigations.

But maybe before we get into the conversation, we can give a give a little bit of background on where you're coming, maybe an origin story. Samantha, would you want to kick us off?

Samantha Pickett: Sure. I started in clinical research about seven years ago.

I started entry level as a CTA, and I was a CTA for a few years.

I was promoted to in house CRA at that same institution and we went under an acquisition.

So, I changed institutions at that point to a site startup specialist. And then I moved into a management position of the CTA team and after that is when I moved to Proxima as manager of study startup.

And just recently I was promoted to associate director of study startup.

Etienne Nichols: All right.

Samantha Pickett: Held a few different positions.

Etienne Nichols: Well, congratulations. That I'm sure that sounds like you have a pretty a great experience all the way through from the beginning to. To managing. So that sounds really good. Maybe we can get into some of that.

But pass the mic to Isabella if you want to talk a little bit about where you are and maybe where you're going.

Isabella Schmidt: Yeah. So, I will try to make this brief. I think a lot of people know me from the regulatory affairs side, so was Director of Regulatory affairs at Proxima, as you may have heard, Etienne said, a different title.

So, what a lot of people don't know is that I actually started off in clinical.

So, when I started in industry, I was also a CTA and then I was CRA and then I did regulatory clinical and then I worked on a bunch of biotech NDA stuff and then I moved into regulatory quality and clinical strategy for med devices.

And then I landed at Proxima where I was actually in clinical first and then I built up the regulatory department at Proxima and so now I have an expanded scope to include all of Proxima services.

Etienne Nichols: Fantastic.

And we were kind of joking about this before we started recording, but just how you have to step jump in your career to really have a, you know, expand what you're doing.

I'm always impressed when people are able to do that. It's like unlocking parts of your brain. So maybe after you're in the role for a few months, just be intentional and thoughtful as you go through this and you can give me a little bit of advice on how you're going through that because it's always interesting to see how people grow.

Isabella Schmidt: The biggest thing for me is to build the people underneath you.

So, underneath being a relative term. I don't like, like the hierarchy talk, but you build up the team and then they take on responsibilities, and you empower them and then they grow and then you're able to level up too.

So, it's a bunch of different leveling up.

Etienne Nichols: Okay. No, that's a really good answer and unprompted too. So that's very cool. I love that you've already been thinking about this.

Okay, so let's talk a little bit about site selection.

And I maybe have a good place to start. Would be the protocol or is that a good place to start? Maybe I'll just, just ask that question. What is. If I'm a, if I'm a medical device company who's thinking about selecting a site, what is the right place to start?

Samantha Pickett: No, that's the perfect place to start. Is, is the protocol, because that's the foundation, that's the source of information for the sites and the rule book for how the clinical trial is run.

Isabella Schmidt: Right.

Samantha Pickett: So, you want to make sure that you have a well written and complete protocol when you start out. That's the first impression that you're giving to the clinical investigators when they look at your trial, when they decide, do I want to participate in this, or do I not want to participate in this?

If you're protocol isn't done, they're probably not going to be interested. We send out feasibility surveys all the time to sites and you know, we can, we send a little blurb about what the protocol is about and you know, it can take a really long time for them to complete a feasibility questionnaire because they don't want to do that until they've seen a full protocol or they can just immediately say they're not interested because, you know, they, they don't know immediately what they're getting into. And it's not the first thing on their mind.

So that's, that is a great place to start.

Etienne Nichols: Okay, so. And we'll, we'll talk a little bit about what it means to, to have a well written protocol. But I'm curious, I want to ask one layer deeper, what you just said, did you call it a feasibility or.

It sounded almost like an executive summary that you would send out. What. Can you go a little more detail?

Samantha Pickett: Yeah, so a feasibility questionnaire.

You know, once we start working with a sponsor, that's part of our process of how we select the sites is we kind of send a questionnaire to see if they're, you know, generally suited for the study before they have a qualification visit, just to gauge their interest.

Are they remotely interested? Are they seeing, you know, the patient population?

Do they have the general equipment? It takes, you know, kinds of things like that to see if, you know, like I said in general if they would be a good candidate to run the trial at their institution.

Etienne Nichols: Okay, so this, this question that we're talking about, it's kind of a two-way questionnaire. It sounds like you're evaluating them based on the answers, but they're also evaluating you. I would.

Is that same?

Samantha Pickett: Absolutely.

Etienne Nichols: Yeah.

Samantha Pickett: Yeah, absolutely.

You know, we want to make sure we're working with someone that has experience in the trial, but we also want to make sure that our trials are a good fit for their institution.

If, you know, if we've got a device trial that's a diagnostic or this one thing, we don't want to be at another institution that's running a device trial for the same thing because it's competing, and we'd be competing for patients and things like that. So, it's got to be a good fit both ways.

Like every relationship, like the relationship with the sponsor and the CRO and the relationship with the site and vice versa.

Etienne Nichols: That makes sense. And I usually, I tend, well, I tend to latch onto something that I think, hey, that's a great idea and I love this, this thought, but maybe I, we're getting a little ahead of ourselves because, and of course, correct me if I'm wrong, is this an output of the actual protocol? Does it make sense to. I mean, I'm just going to go, go through this and you tell me where I'm right or wrong. It seems like it would make sense to write the protocol, and this questionnaire would come later based on the content of the protocol.

Is that accurate?

Samantha Pickett: Yes, absolutely. So, we develop that questionnaire essentially from the pieces of the protocol that we need the patient population, you know, are they able to run this trial at their institution? And we, we can't ask them those questions if the protocol is not complete.

And we know what we need to run the trial.

So having that complete protocol is the very first step in site selection is. So, we have the rules of the game, basically.

Isabella Schmidt: Well, and if we don't have a protocol, we kind of don't even know what types to reach out to. Right. So, we would need to know, hey, this is an indication.

This is what the indication is. This is kind of what we're doing. So, we would need a protocol. And I guess like you're saying, Sam, if we don't have a protocol, it's also hard for us to know when to begin to reach out to the sites, because we don't want to reach out to them a year before the study is actually going to happen, because then it's just a waste of our time, a waste of the site's time.

So having that protocol at least is a first step to being serious about the trial. Right. And not just saying, oh, I'm going to do this trial at some point and some indication.

Samantha Pickett: Yeah, that makes sense. Exactly.

Etienne Nichols: Okay, so I'm sure some listeners are saying, okay, Etienne, just get to the actual question of what we need to know. So, the actual protocol, what.

When you see, you've probably seen a lot of these different protocols. When you say a well written complete protocol, what's the difference in that? And what you might say is that one's not well written.

What are the differences or common pitfalls you see people getting into with this.

Isabella Schmidt: Regulatory.

Samantha Pickett: Would you like to take that question?

Isabella Schmidt: That's a really big question, Etienne.

So, let's talk about it.

One is, you really want to design your protocol to address the patient population and the intended use that you're trying to get a labeling claim for. Right. So, you need to be intentional about who is going to be using the device, how it's going to be used in that patient population, what your study objectives are, what your endpoints are going to be, and then you also want to make sure that you have comprehensive schedule of assessments.

So even at the very early stages, sometimes we'll do what's called a protocol synopsis, where you're basically outlining the high-level things, how many patients there are, what are your objectives, how many sites you think you're going to need.

Sometimes maybe you have ideas of some sites.

You're obviously a title in the protocol and some of the analysis that's going to be planned. Another good thing is to do the schedule of events or the schedule of assessments, which is basically all of the activities that are going to happen during that clinical trial.

And that's really important for like, Sam, to know kind of what facilities does the site need, but also for like budgeting of the clinical trial, because depending on how many assessments there are, that could, you know, tend itself to more what we call case report forms, which is probably the data management discussion that we talked about earlier, which would also be indicative of how much monitoring, which is another discussion in and of itself is necessary. So, it also has a lot to do with the budget, but and then also the site.

So how much time does the site need to allocate to this study, which also has to do with site selection? So, I'll pass it back to you, Sam.

Samantha Pickett: Yeah, the budgeting piece for the sites is really important.

That negotiation can take a long time. There can be a lot of back and forth if things aren't clear what standard of care, what is required for the protocol, what kind of information are we just going to obtain if you happen to have it as an institution, but we're not going to make you run this test as part of the protocol.

So having that well written protocol, again, having that schedule of assessments of all those activities is a really important piece of how quickly things can move with a site when, when you're getting them started because of, because of those different types of discussions.

Etienne Nichols: Okay.

Isabella Schmidt: I think one thing that she said right there was like what we're going to make you do versus what you're just going to maybe do anyway, and can we collect that or can we not?

We're not going to make you do it. I think understanding the level of importance of those things is important because you need to understand the analysis and what data elements are important for you because you do want to enforce those things are collected.

Right. So even if it's not part of what they would routinely do, you probably, if it's really important to get to your endpoint and your study objectives, you really want to be able to collect that data.

And so, when we talk about selecting sites, we want to make sure that we're selecting sites who are willing to do that or capable of doing.

Etienne Nichols: Yeah. Okay, that makes sense. And I appreciate you all letting me kind of anchor to this. You know, the protocol, when I know if we zoom out the, the, the broader discussion about selecting a site is, you know, maybe a little bit different, but it starts somewhere. So, I like to, I like to start maybe where A company would start.

Okay, so now that we've, let's say we've got our well written protocol, what's the next step in selecting a site?

Is it the questionnaire? Is it, is it evaluating sites? What's next?

Samantha Pickett: Yeah, so we, we always want to come together with a sponsor if they already have relationships with sites that, you know, they've had in mind or we as a CRO kind of evaluate our bank of sites that we worked with to see if any of those would be a good fit and recommend them.

But either way, whether we have to find new sites or use an existing relationship, we send out feasibility questionnaires to see who's able and who is a good fit for the site.

Well, first let me back up. We negotiate non-disclosure agreements, that is clinical trials 101.

Negotiate that and then we can do the feasibility questionnaire, send them the final protocol. And the final protocol allows them to give us the most accurate information because they have those details of what needs to go on in the trial so they can reply to the feasibility questionnaire more accurately.

And then if a site, if it seems like it'll be a good fit, then they'll move on to a site qualification visit, which is kind of what we're, kind of what we're doing here. It's just like a monitoring visit to see if, to, to be more detailed about the things to talk with the principal, principal investigator and see, you know, do they have enough staff to run the trial, which is extremely important.

If they don't, you know, if they don't have a study coordinator at the time, that trial is not going to move very fast because a PI can't do everything on their own.

They need a study coordinator helping them, you know, screen for patients and things like this.

And also, you know, see if that site is going to provide enough patient diversity, which I think Isabella wants to talk a little bit more about that because it's becoming, it's becoming more and more important in clinical trials.

Isabella Schmidt: Yeah, yeah.

So, I can add about the diversity, but also just to note, NDAs are important in clinical trials, but they're important in everything. Don't talk to anybody without having an NDA.

Don't share any information.

So, the diversity, okay, so diversity in clinical trials is important and this is, you know, tying into the site selection conversation too, and the protocol conversation because you need to understand what the diversity is expected for your product and for your patient population.

Right. So, you can kind of do that in different ways.

The best way to go about it is if you can get epidemiologic information about the disease state and the different minority groups, you know, whether it's race, sex, gender, socioeconomic status, all of that about that particular indication, particular space, that's the best-case scenario. Now, a lot of the times that information is not available.

And so, then what you typically default to is what's the representation of the general population of the United States, if you're in the United States or wherever it is that you may be, and kind of making sure that you're able to have representative numbers of the patient population, whether that's the disease state or the United States within your study.

Obviously, this is because historically, a lot of clinical trials were not tested in a representative patient population.

Mostly white men were in clinical trials. And so, the tests were not necessarily applicable to women, to Americans, Hispanics, et cetera. And so now we want to make sure that any devices and drugs are truly able to be efficacious and safe in the real, you know, the full patient population.

And so, when we think about site selection for that, we want to make sure that we're going to sites that either have a good socioeconomic, racial, ethnic distribution, so they may be in, you know, cultural hotspots like Houston or Chicago Place, Los Angeles, big cities like that, or you're going to locations where you have large numbers of certain minority groups to kind of balance it out within the entire study.

And there are lots of different, you know, besides psych selection, there's things that you can do during the management of a clinical trial to kind of maintain that you're actually getting that good distribution within the patient population that's very deep and detailed.

And we probably don't want to go into the nitty gritty of that, but it's, you know, stratification and paying attention to the enrollment and all of that within the sites and just keeping a close eye on that. And so, what you want to do is kind of plan what your diversity needs to look like at the front end of the clinical trial and how you're going to ensure that that diversity, the diversity. What's the word I'm looking for? Requirement is met, and then how you're going to monitor that throughout the trial and any sort of risk mitigations that you're going to be putting in place to ensure that you're able to get a truly representative.

Etienne Nichols: That makes sense. And I know the FDA put out a guidance on enhancing the diversity of clinical trial populations. I think it was 2020. I feel like there was Something more recent.

Is there, has there been something more recent or am I mistaken?

Isabella Schmidt: Draft guidance that came out recently. It's very short, honest, and it's just kind of basically further talking about how to enhance diversification and, and that they're putting more of an effort to this. And, and so they're really looking more into the diversity planning to kind of address what the historic challenges were with seeing equal representation.

Etienne Nichols: Okay, I know there's a lot of different aspects. I do want to ask one little, one more question around the diversity and choosing your site.

So, you mentioned Houston, a few other geographical, diverse places within the United States. What are your thoughts about.

Maybe I'm a US Company, but I want to go maybe for economical reasons. Maybe I'll go somewhere else. I know historically people might have tried to release or do first in human.

Overseas and in Europe.

A lot of companies now are talking about maybe Latin America. What are the pros and cons of some of the site selection on a more broad global.

Looking at it globally, what are your thoughts?

Samantha Pickett: Things can definitely get a little more hairy because, you know, Europe has different regulations to follow. So, if you're kind of running dual in the US And Europe, it can get a little more difficult, you know, because the European sites are held to different standards than the American sites are.

So, we try, you know, our, our best to, to get the diversity within America. That is part of the very beginning of study startup is that's one of the things we look at is we are trying, like Isabella said, to address the diversity up front.

So, we, we've got the epidemiology of, you know, the United States for the disease, and then we also have kind of where the minority groups are more, you know, concentrated and mapped out. So, we definitely try to hit, you know, Florida and Texas for Hispanic population, Southern California, you know, the Pacific Northwest, New York, and then, you know, just different hotspots around the country that have those pockets of more diverse populations.

Etienne Nichols: Okay, okay, now that makes sense.

Um, so if, if we go back to the conversation about. We're, we're interviewing the, the, the, the site and we're talking to them about different things. One of the things you mentioned was that clinical manager.

So, I'm curious a little bit about what this actually happens on a, a tactical level. You said you go to the site, have that interview with these different people. How do you, how do you ascertain whether or not they have the bandwidth, the correct equipment, so forth competing studies even I know you mentioned, how do you go through and ensure that all of that is going to work out.

Samantha Pickett: That's all part of that site qualification visit process. We're talking to the PI, the person that's going to be responsible for all the things on the trial, who's signing their name, saying, you know, these things are accurate.

So, you know, we talk to them like, are they, does this institution have other competing trials? Like do they specifically have, you know, do they have a coordinator? Do they have a backup coordinator in case that person gets sick, or you know, are they having a lot of staff turnover?

Do they specifically have X, Y and Z? From the protocol we have a study we're running right now, they specifically needed a negative 80-degree freezer. So, we, you know, when we're talking to the site, do you have one?

If you don't have one, do you like, are you open to one being rented for you? Do you have space to put it? Do you, you know, all of these things, you try to take as much into account upfront as possible.

Once you get past that feasibility like, oh, are you interested? Could this potentially be a good fit that these, that site qualification visit is really getting down to the nitty gritty of are we serious, you know, are we serious about this?

Are we going to move forward?

Do you have all the things that you need to run this trial successfully? If you don't have them, how can we get them to you?

Or do you not have enough of the things that we should just stop here and move on to another site?

Isabella Schmidt: I want to add something just the site selection process is really important and what I'll see a lot of the time is startup companies will want.

Samantha Pickett: It foreign.

Etienne Nichols: If you can hear me, I'm going to pause the recording because I'm.

It cut out for a moment. So, hold on just a moment.

Hey guys. I may have had some Internet issues, so apologies for that. We're back on though and Isabella had just started talking a little bit more about site selection. So, I'll let you, if you remember your train of thought, I'll let you go.

Isabella Schmidt: I will try to recreate it. Okay. So, I was saying that site selection is a critically important part of the clinical trial, and I think that it may not be emphasized enough.

A lot of times what we'll see with startups is that they will have sites that they have pre-existing relationships with and want to use those sites in their clinical trials.

And sometimes that works and sometimes it doesn't.

It's really good for these sites to have these relationships with these docs or these kols.

But that relationship doesn't necessarily mean that they're a good fit for the particular clinical trial.

So, what happens is because they have these relationships, they want to lean on the relationship a whole lot to get the trial to run smoothly.

But there are a number of different factors that go into site selection for a clinical trial that Sam has been mentioning. And sometimes the sites don't have the support that they need.

So maybe they have the research staff that's trained in that area, or maybe they don't have research staff at all. And maybe they don't have the patient population. Right. So, they may have some patients, but they may not have enough to really hit the enrollment criteria for the trial.

And so, it's really great to have those relationships. But I wouldn't default, say, just because you have the relationship, that that necessarily means that that physician is a good fit for a PI for a clinical trial, or that that site is a good fit for the clinical trial.

And so just speak. You know, I think going through the site selection process and not just defaulting to having sites that you already know be a part of your study is important.

And in addition, on that, I think folks need to remember that when you select sites, the sites are working for you. You're paying the sites to do the study. Right.

So that means the sites are going to need to be managed. Right? Just like you would with any employee, any team you want to manage, make sure that they're doing things correctly, that you're interviewing them.

They're like, that's what the site qualification visit and the feasibility questionnaire and everything is. You can think of it like an application process, right? Like, do they like going through your application process?

Do you like what their application says? Are you going to take along an interview? Right. And so that's what the site qualification visit is.

You want to make sure that it's a good fit and that they are a good fit for the study. A good. And that they continue to be a good fit throughout the trial.

So, it's not we selected them and then we're, we're done monitoring them. That's all the clinical monitoring stuff. That's, you know, keeping track of how everything's going, really reassessing the site as the study progresses and, you know, making changes or addressing things as it goes along.

But the first step is really making sure that you got that good fit in the door the same way you would with, like, any hiring process. Right? Because if you got a good fit in the door, then hopefully you don't have a whole Bunch of issues later down the line that you need to address.

Etienne Nichols: And what does that look like, the reassessment? Do. Do you actually have an employee go out and look at that, or do you recommend during the study.

Isabella Schmidt: Samantha?

Samantha Pickett: Yeah, we do, you know, injury monitoring visit. So going on site, they can, you know, make sure that they're keeping their equipment up to date and making sure, you know, they. That's what an IMB is, is for the CRAs to double check things and make sure that the site is running things, per protocol, the way it's supposed to be run.

And if they're not, then, you know, if an offense is serious enough, then they can be closed down. And like Isabella said, you know, finding sites that are working properly, that are enrolling patients, that's a huge deal.

I've seen so many sites just closed because they're not enrolling the patients that they said they would or they thought they would, because the sponsor, they're still paying them money to search for these patients.

But if they're not producing patients and the sponsor is essentially just wasting money, so, you know, they'll close down a site for low enrollment as well.

And to piggyback on what Isabella was saying about, you know, sponsors assuming or defaulting to using those relationships they already have, I mean, I'm sure we've both seen it, you know, go south.

You're.

When you choose a site, like, you're going on a journey with this site, and if they're being, you know, difficult in the beginning, if they're not giving you things on time like they said they would, you know, do you. Do you want to deal with that for the entire rest of your study?

Because, you know, it's. The protocol is the site's first impression of the sponsor. But then, you know, the sponsor and the CRO also take their first impressions to account as well.

If a site's difficult upfront, you can just assume they're going to be difficult the entire time. And do you want to take that on?

Etienne Nichols: Yeah.

Isabella Schmidt: Yeah. And I would add to that.

Samantha mentioned the competition earlier, too, as a big factor when you're selecting sites, because.

Well, first of all, you want to know, not only do they have competitive studies, but how many studies are they assigned? Like, is the coordinator assigned or how many studies does the site have?

Samantha Pickett: Do they have time to run your study?

Isabella Schmidt: Yeah, because the resourcing is restraining for sites as it is for everything now. Right. So, we've had a lot of, um. We've seen strains in resourcing across industry across FDA, across site, across everything. Right. So, the great resignation happened. Now we're having a lot of people getting laid off all over the place.

So, there's just resourcing issues across the board, I think. And that also impacts sites. And so, you want to make sure that they don't have too many studies for the staff to support them, that they do have the time, like Samantha said, because of a lot of the, you know, not only for your study, but for the staff as well. Right. Because they'll get overwhelmed with having too much to do.

And so, you'll see that. That they have so many studies that they're overwhelmed. And if they're overwhelmed, that's not a good situation for anybody. Well, even if they're trying to give you the time.

Right. Even if they're going for giving you the time, that's a recipe for mistakes to be made for oversight.

So, you really want to take a look at how many sites, my site, how many studies does the site have?

Are they competitive?

Because that's also a place where you'd have enrollment potential issues. If they're competing for one, you know, that's, you know, multiple studies that they're trying to target the same education, but also a place where they could, if they're overwhelmed, be making mistakes, confusing things between the similar studies.

So, you just want to be mindful of all of those things when you're selecting a site. And that again, goes to the fact that you might have this Kol, but you may have competing studies.

So, you don't necessarily always just go to the site that, you know, that's.

Etienne Nichols: A, that's a good point that you made. I mean, even if it's not competing, if it's a similar study, you're dealing with human beings who may make this. Well, this is the same thing as I'm doing over there. So, this is probably what they want. And I can see the.

That human cognitive error taking place at times.

So, if I were to shift gears a little bit earlier this year, we did a survey of, I think it was 613 MedTech professionals to talk about challenges with the industry and things that people are facing for 2023, and maybe I'll put that a link in the show notes to that study, if anyone's interested in looking a little bit more closely at that. But one of the things that was mentioned was the disparity between what we think or how long we think it will take to get to market and how long it actually takes and timelines.

We are so bad in this industry at estimating our timeline. So, I'll get to the point on the question I want to ask and that is what is, what is what are one of the biggest impactors of timelines?

Because I know as a project manager, I remember the study was one of the things that felt like was completely out of my control. And so, I was guessing or taking a stab in the dark.

What are some things that impact timelines when it comes to these clinical investigations?

Samantha Pickett: Oh, timelines.

The ever changing. Right.

It's, there's so many moving pieces in a trial and timelines are, they're targets, right?

They're. Nothing is written in stone. Anything can happen.

Sometimes anything that can go wrong does go wrong.

And we're like you said, we're all human beings, right. So, we are kind of, there's room for error and we're kind of at the mercy of, you know, process and guidelines and things like that.

I think it's really, really important for sponsors to go into it with realistic expectations of timelines.

Sometimes, you know, we get sponsors and they're like, you know, we want first patient in by March and it's January and we're just like where, where'd you come up with that? You know, oh, we, we just want first patient by March.

Well, like there's processes we have to, you know, follow. There's. The sites have their processes that they have to follow.

It's always, you know, nice and you know, you get the clout for having this large, big-name institution participating in your study. But with that large, big-name institution, they are large, big-name institution because they're a well-oiled machine. They have their processes that they go by. They probably have a local IRB that they use, and they probably have separate budget and contract committees and they, you know, things just take more time. It could be a linear process instead of a parallel process and it can just take longer and longer to get things started at that institution.

Etienne Nichols: And there have been a few acronyms. I, I apologize for not getting this clarified earlier. But. So, IRB, Internal Review Board. I know there was another one. IMB or IMA. I may be misremembering that.

It doesn't matter. We'll, we'll look at it later. But anyway, I'll try to, I'll try to catch the, the acronym. So, the local IRB that you mentioned. So, what are some different options when it comes to selecting a site and utilizing an IRB?

Kind of enlighten me there if you could.

Samantha Pickett: Yeah, so there's local IRBs and central IRBs.

Central IRB is typically faster.

A local IRB can be, you know, this one institution has their own IRB, or this group of institutions have their own, you know, review board that they.

Etienne Nichols: Go through, which would be essential for that group. Is that right?

Samantha Pickett: Or, or no, sort of.

The language can get a little confusing. A central IRB would be for like a multi center study.

And then each site can some groups or sites have agreements with the central IRB. Yes, we'll use you, you guys, you know, if somebody, the trial wants to use you, we'll use you.

Or yes, we'll use a central IRB if X, Y and Z criteria are met or no, we just use our own local IRB. So, we make sure that everything is going the way we want it to.

And the purpose of the IRB is, you know, protecting patients to make sure that everything is, patients are aware of what's going on in the trial, what, you know, risks and benefits and just to protect their privacy.

And everything about the IRB is patient focused.

So, the IRBs, like they kind of all have the same standards. Local IRBs can have a little more stricter standard. They can have specific language that they want used that's presented to patients and all those things can kind of take a little more time.

The central IRB, if a site uses them when just say you have six sites on a trial that are using the central IRB and there's a protocol amendment, you submit that protocol amendment with any other additional updates to the central IRB and when it's approved, it just gets approved automatically for those six sites.

So, it's much faster than those six sites having to submit to their own local IRBs and then we have to wait for six different time points to get approval for the central IRB.

It's kind of all approved in, in one go and then we can just move forward a lot faster.

Etienne Nichols: Okay, that makes sense. And so how do you. Well, what kind of recommendations do you have for a medical device company who's trying to select their site and they're weighing the options between these different things.

And maybe the specific pain that I'm thinking about is I created a protocol, I'm going to send it to this.

Maybe it's a local IRB and a central, because I have, they're outside the scope. And so, I'm doing multiple, I'm assuming that's maybe a situation that you run into.

What if I have a situation where I need to change the protocol? What are, you know, how during, halfway through the study, how does, how do those changes get disseminated across multiple sites? And I don't know if you could just kind of elaborate on, on how to overcome certain specific challenges with a multi-site study.

Yeah, so that long question policy that.

Samantha Pickett: Happens, that happens all the time.

I prefer to utilize central IRB whenever possible. That's going to be. The sites are going to get up and running usually faster.

We kind of use a two-tier approach. Like these are the sites that are going to get up and running fast. But then we also want these, you know, academic sites that, you know, have this really big patient population and they're going to boost, you know, enrollment and things that might take a little longer. So, we get the ones up running faster that might be a little slower to recruit.

And in the meantime, we're getting the ones that take longer started up and then you'll get a bolus of enrollment later.

So, we kind of take that two prong approach.

And then when it comes to protocol amendments and things like that changing in the middle of the study, like I said, you just submit to the central IRB and those sites, get it done.

And then we have site startup specialists and our CRAs also, if the site's already active, just going through and helping the sites with the local IRBs, making sure that they submit and get the new information, you know, approved and up to date.

Etienne Nichols: Okay. Anything else about timelines and things like that that you would maybe recommend or not? It looked like you were going to say something. Isabella.

Isabella Schmidt: So, one thing about the academic sites and KOLs too is sometimes you have the situation where they have this large patient population.

You also sometimes have a situation where they're slow enrollers. Right. So, you may spend a year trying to get this site up running and then a year getting two patients and all the other sites are like, oh, I've got so many patients and they're kind of like hitting enrollment and then they may only have like a handful of patients, but you still want that site because you have a KOL at that site.

Kol still wants it because he runs up on the.

And so, there's this sort of symbiotic relationship there. So, it still benefits you to have it because you want that KOL and he wants the publication. And so, you know, just be mindful that the site may be a slow enroller that, you know, just because it's a KOL doesn't mean that the sites can enroll a whole bunch of patients.

Sometimes they do, sometimes they don't.

And so you really want Like Sam was saying and kind of you were hinting at that you really want a balance of, okay, I have these KOLs whom, whose sites might take a really long time to get up and running because I got local IRB and all this bureaucracy getting contracting and all of this stuff in place.

And maybe they're a slow enroller or maybe they have a really great large patient population. But I also have these other sites that are not necessarily the KOL is not necessarily the academic institutions.

They can go run through the central IRB and I can get them going really fast.

And if you really want to have patients that come from the sites that, you know, have these KOLs, just being mindful of, not like exploding the patient population in one site.

And that's part of that sort of diversity planning too, right? You don't want to have one site that it is so, so good at enrolling that they enroll the entire study.

And you don't have diversification throughout the United States and the study, the sites and everything because you don't want it to. If it's a multi center study, you don't want it just at that one site.

And FDA is not going to want to see that if they agree to a multi center study.

Make sure that you're balancing it.

Etienne Nichols: Okay, sorry to interrupt.

You bring up a really good point. And that is kind of like diversifying your portfolio of trials or investigations. Because ordinarily I might think just as a, maybe I'm a project manager or something, I might think, well, we just have to get through this investigation so we can get to the next one so that we can get to market.

When in reality it sounds like there's a little bit more of a bureaucracy, political side, from the business side, the business standpoint, we've been util. We've been utilizing these key opinion leaders, we've been utilizing these, these specific sites for other relationships. And so, you want to maintain that and maybe that's going to help you even post market when, when you're actually trying to get into the hospital.

And so, for like that. Is that accurate?

Isabella Schmidt: That's accurate, yeah. Having KOL advocates is always beneficial. I mean, you want to have the disposition advocates out there for you at the sites and just like in the industry in general.

So yes, so. So, you want to balance that out. Some of it is like I was saying earlier, even if you're not going to use them in your study, you still want to maintain that relationship.

Maybe use them in some other type of study, maybe use them in a post-market setting, study where it's a better fit. You really want to make sure that you have the good fit for the study.

And sometimes you go into that knowing, okay, this site's going to be a slow enroller, that's okay, I know that.

But you really want to still make sure that they have all the other things that they need to be able to conduct a study. Right. They have adequate research staff; they have the facilities that they need.

It's not going to be this, you know, major headache bringing them into the study.

And then you had asked about timeline, and I don't know if you just hinted on it now or thought you were going to, to Sam's point, there's all these moving parts into getting the study started up.

I think there are so many different factors that go into the timelines that the companies are thinking about.

There's on their end, funding, right. So, they're like, I've got this protocol, but they don't have the funds to kick off the study.

So that's one thing. So, the timeline of funding and that's really hard for them to predict. Right. They may think that they're about to get the investor to sign, maybe they signed an LOI, but then, nope, the investor pulls out. You just don't know. Right. So funding is a hard thing to anticipate. So, we usually what they'll do is think about the timelines outside of that.

But you need to get all of your dots in a row up to the point of the clinical trial.

If you have an, if you have to file an IDE with FDA, you need to make sure that you're getting rolling on that, that you got everything that you need, that you file that IDE with the FDA.

Most cases you probably want to anticipate a little bit longer than that 30-day timeline.

However, we've had it approved within 30 days.

But. So that's one part. But then all of the things that Sam was talking about, it depends on how many sites that you have that you need to start up to get the study readily rolling.

Right. The types of sites that you're getting started up, how quickly they're able to enroll, how eager the sites are to be on the study, and then the enrollment process throughout the trial too. So, there's that startup chunk that we've been talking about that takes, I don't know, Sam, like three to six months on average, probably, right?

Samantha Pickett: Yeah. For central IRB sites, you know, 812 weeks, three to six months.

But for larger, you know, institutions, especially academic ones, it could take, it could take six, eight months, sometimes even a year to get started, just to get through all the processes.

Isabella Schmidt: And that's, that's, you know, and what we're hinting at too is like that's largely a part of picking the sites as well, right? So, like you need to understand those timelines because that's not something that we can necessarily control.

It's within the site too. So, it's a balance of us engaging with the site. So, if we were just like chilling and not doing anything, of course it's going to take longer, but, but it's also some things that are just outside of the sponsor's control, outside of the CRO's control, it's site.

So that's one thing. But then as you move through the study, you, like we were talking about, you got to pay attention to enrollment, you got to pay attention to what the sites are doing.

Because if you're not hitting your enrollment numbers, then your study is going to be dragged on for longer. So, what Samantha was talking about before was if you close down a site because they're not enrolling and so you're paying them to keep the site open.

But so, but they're not enrolling, so you're just paying them to keep doing it. But you're not hitting any of those milestones that you need to hit.

So, then you might need to start spin off another site, right? So, then you have to go through the site selection if you haven't already selected those sites and the study startup, not study startup, site startup process, again.

So, you just are kind of viewing these things throughout the entire clinical trial.

So that can also impact the timeline. If you have slow enrolling sites, if all of your sites are slow enrolling, or if you were banking on this one site's going to be my top enroller and they're just not hitting it, that can slow down your trial overall. Contrarily, if you have awesome sites that are all enrolling like crazy, your trial may finish earlier than you originally anticipated.

So, it's a lot of the, the CRO working with the sites to manage how quickly they're enrolling and to manage all of the sites collectively for the study's enrollment overall. So, so managing like we're saying, if the site's a slow enroller, do we close this site?

Do we need to add a new site? Do we need to help them with enrollment? Right. Do we need to get marketing out there? Do we need to reinvigorate their interest in this trial?

Cause sometimes what you'll see is a site's doing really great and they're enrolling, enrolling, and then all of a sudden, they kind of like dip, right? Or they start to dip and it's.

Maybe they're distracted with a competitive trial or something, or something bright and shiny is distracting them. Now particularly, you see that with trials that have really long periods of time that they're ongoing.

So, stuff like that, you're always managing. I mean, that kind of goes in more to like the entire clinical trial management, but it, it impacts when you're starting up and maybe spinning off new sites or closing them down.

Okay, all balance.

Etienne Nichols: So, we kind of talked a little bit strategy. I want to get one last tactical question in because I like focusing on the things that I can control. But, um, and a lot of times I look at this, you know, we, we've done protocols on paper before, and I know there's other options now.

What is the most technological way to do this, to have the most efficient process? Is there, are there any tools you recommend or things that you use to handle this, especially with multi. Multi sites?

Samantha Pickett: My favorite tool is having a 21 CFR compliant e-signature system.

And you would not believe how many people I just have, like, I get the blank stare, like, what's that?

So that's one red flag that we're going to have a little bit of trouble with the site. But after, you know, after the pandemic, we were forced to do so many things remotely and it's just so much faster to be able to, you know, get a PI signature.

You just send it through your system, it's signed, and then you email it right back to the CRO and instead of having to physically take it to the PI's desk and then we have to wait for them to rifle through all the papers and sign that one and then give it back to us.

And then we have to fax it or, you know, scan it in and email it. It's just so much faster. The E signature keeps things moving so fast that it's been amazing how much faster that is.

And some sites, you know, they still. That that's a question we ask in feasibility. You know, do they have these systems in place, or do they still use paper forms or paper medical records?

Being able to do remote site visits, having electronic medical record, those kind of things are revolutionizing the clinical trial world because it can be not hands off in the sense that, you know, just letting things go, but, you know, it's saving the sponsor money for the CRA, not have to travel to a site and you know, and we, they can get a lot more done, you know, online for eight straight hours sitting, you know, at their desk. If we can do a remote site visit every now and then instead of, of having, you know, take a whole day to travel to and from a site.

So electronic systems are fabulous.

Etienne Nichols: So basically, what you're saying, if I could sum up is a post if in your site selection part of the criteria is a post-pandemic 21st century software that you're using.

Something like that.

Samantha Pickett: Yes.

Isabella Schmidt: Tech savvy is the question.

Samantha Pickett: Yes. It accelerates the timelines is what I'm saying.

Isabella Schmidt: I don't know what the e-signature is.

Samantha Pickett: Yes.

Etienne Nichols: Excellent questions for that question that we're talking at the very beginning.

Okay. Anything we missed. I know it's we, we need to wrap up, but I really appreciate you joining the conversation or carrying this conversation, presenting it for us and anything we missed or you want to last.

Last little words you want to throw out there.

Isabella Schmidt: I do have one.

Back to your question about the OUS trials.

So usually what we'll see is sponsors do that as a first in human study.

It's less expensive, et cetera.

First in human. Sometimes that's okay because it's not your pivotal trial and your criteria for selection may be somewhat different. You’re probably doing that more for investors than for regulatory.

Sometimes you might be able to use it for regulatory.

I would say never plan on doing that for your pivotal trial. Only OUS.

At least if you want to do a global trial, that's okay, but only OUS.

What typically happens is FDA wants to see US Population and particularly if you're going to a location that is not diverse ethnically.

So, if you're going to somewhere where regardless of whether it's, you know, all Caucasians or it's all Asian or whatever it might be, they won't typically accept that data. And it's really just a challenge to get them to agree that whatever that the racial differences and the ethnic differences and not really gender, but those differences when you're moving OUS don't impact the use of the device.

It's a lot easier to say no than it does say yes.

So, I would just make it as easy for or as hard for them to say no as possible. And it's easy for them to say yes as possible.

So just plan once you're getting into pivotal territory and maybe even pilot that you're. You're at least having some and a good number of US sites of US is your rule.

Etienne Nichols: I think that's good advice. Samantha, any. Any last piece of advice?

Isabella Schmidt: Oh, no. Tina lost her sound.

Etienne Nichols: Not again.

Isabella Schmidt: Yeah, I can't hear you either. Oh.

Etienne Nichols: You can't hear me. Okay, hold on.

Isabella Schmidt: You were thanking us for such a wonderful podcast.

Etienne Nichols: I was thanking you so much. Can you hear me now?

Isabella Schmidt: There you are.

Etienne Nichols: Ah. Okay. We're going on record for having the most issues with sound on this one. So, you did break some records. Thank you so much. Samantha, I was going to ask any last piece of advice that you had.

Samantha Pickett: Yes, I read this somewhere. I don't remember where, but it's profound in its simplicity. You know, for a study startup, you really.

You really like. Isabella was saying before, as much stuff in front as possible.

So, you know, try to do it right so you don't have to do it again.

It's kind of the takeaway. We really tried to strive to, you know, get all our ducks in a row and select the best sites, you know, for all of the different reasons, you know, so we're not closing and reopening, wasting time, wasting money, wasting effort.

So, we really try to do it right, so we don't have to do it again.

Etienne Nichols: Fantastic. Well, thank you both. We'll put links to their LinkedIn as well as other ways to get ahold of them. However, they would like that in the show notes. So definitely check out the show notes after Samantha.

Isabella, thank you so much for being on the show. We'll let you get back to the rest of your day. Thank you so much. Take care.

Isabella Schmidt: Thank you.

Etienne Nichols: Thanks for tuning in to the Global Medical Device Podcast. If you found value in today's conversation, please take a moment to rate Ruth review and subscribe on your favorite podcast platform. If you've got thoughts or questions, we'd love to hear from you.

Email us at podcast@greenlight.guru.

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