In the next episode of Clinical Trials Spotlight, host Andrew Pucker, OD, PhD, FAAO, is joined by clinical research experts Kim Williams and Amy Brown to explore the critical role of site selection in ophthalmology and optometric clinical trials. They discuss what sponsors and clinical research organizations (CROs) look for in research sites, common challenges encountered, and best practices for building successful studies from the ground up.
Andrew Pucker, OD, PhD, FAAO:
Welcome to Clinical Trials Spotlight, the podcast where innovation, research, and patient care come into focus. I’m Andrew Pucker, Chief Development Officer at Mintra Health and your host for this series exploring the latest developments in optometry and ophthalmology clinical trials. Each episode, we’ll sit down with leading clinicians, researchers, industry experts, and innovators shaping the future of eye care. From emerging innovations in study design, patient outcomes, and regulatory insights, we’ll take you behind the scenes of the clinical research transforming optometry and ophthalmology.
Whether you’re a clinician, researcher, industry professional, or simply passionate about advancing vision science; this podcast is designed to bring you thoughtful conversations and practical insights from across the ophthalmology and optometry community. Clinical Trials Spotlight is co-produced by Mintra Health and Ophthalmology 360 and Optometry 360. Thank you for joining us. Let’s get started.
In this episode, we’re diving into the site selection, how sponsors and CROs identify the right clinical sites, what makes a site successful, and why these decisions matter so much in ophthalmology research. Our guests today are ophthalmology clinical research veterans, Kim Williams and Amy Brown. Kim, could you please introduce yourself?
Kim Williams:
Hi, I’m Kim Williams. I am a project manager at Mintra Health with many years of ophthalmology experience and have worked quite closely with our other guest, Amy Brown.
Andrew Pucker, OD, PhD, FAAO:
Amy, could you introduce yourself too for the audience?
Amy Brown:
Yes. Hi, I’m Amy Brown. I have a degree in pharmacy with over 20 years of experience in community practice. For the last 8 years or so, I’ve been involved in clinical research, working a lot with Kim, supporting clinical trial activities and research operations with CROs that specifically focus on ophthalmology.
Andrew Pucker, OD, PhD, FAAO:
Awesome. Thanks for being here. I’ve worked with Kim and Amy over the years. Wonderful people, very knowledgeable. We have the perfect guests for today’s topic, which again is site selection. Let’s kind of start from the beginning. What makes an ophthalmology site selection unique in this indication? We know there’s cancer research, ophthalmology research, lots of different things out there. Why is ophthalmology different? Maybe Kim, you want to start.
Kim Williams:
Sure. I think we work with quite a few private sites versus larger universities. We do work with large universities, but I think most of the trials that I’ve worked on have involved private sites and they also seem to focus on certain disease areas. Gene therapy, dry eye disease, some sites will mostly be interested in contact lens studies, if you will, just device studies. I think that is how they differ from other therapeutic areas.
Andrew Pucker, OD, PhD, FAAO:
It seems like you need to have some very specific knowledge in certain aspects and eye care is not necessarily just the eye. It’s like front of the eye, back of the eye, and people have their camps, right, and you need to pick the right people and know the right people to pick from the beginning.
Kim Williams:
Yes, definitely. We’ve found that it’s better if you have an ophthalmology site that has a separate clinical research area so they can have dedicated staff. Not all of your ophthalmology sites are going to have that.
Andrew Pucker, OD, PhD, FAAO:
Building off something you said, Kim, and maybe Amy, you want to answer this. There are private practice sites and university sites, and it sounds like they’re different. Why would a sponsor pick one over the other?
Amy Brown:
Yeah, that’s a good question. It’s much easier to work with privately owned sites, basically because of the red tape with universities. Universities typically have their own regulatory board. A lot of times that comes with getting approval from the university regulatory board for that particular investigator to do a study. That takes a long time. Given that most sponsors have time requirements, it could take the whole study to get an investigator on board to actually do the research study for that sponsor. A privately owned clinic doesn’t have that red tape. They typically will use a regulatory board that’s been chosen by the sponsor or the CRO that they’re working with and that seems to escalate the amount of time it takes to get them up and running to do research.
Andrew Pucker, OD, PhD, FAAO:
It sounds like a private practice site might start up in like 2, 3 months, whereas a university, which I used to work at, could take 6 to 9 months in some cases.
Amy Brown:
Or longer. Yes, absolutely. Absolutely.
Andrew Pucker, OD, PhD, FAAO:
Timelines are a huge, huge factor, but what are maybe some reasons you would pick these university sites? They do have some value and we like working with them, right? But why would you pick them for a study?
Amy Brown:
Yeah, there could be a couple of reasons. Some of the reasons could be that investigator, maybe a KOL, somebody who actually knows that particular therapeutic area where the sponsor is looking to do the research. The other thing is that universities typically have access to labs and equipment, things that may be necessary for their study versus a privately owned clinic who may not have all the equipment needed or access to a lab for their study.
Andrew Pucker, OD, PhD, FAAO:
I think that makes a lot of sense. You have people at an academic center, they’re probably doing research full-time, 4 days a week. They’re reading papers, and they may have a little additional knowledge on a topic than say your everyday private practice doctor who’s seeing patients most of the time. That sounds like an important thing to consider. Going along those lines, we’ve talked about a couple of factors sponsors might consider in site selection. What do you think are the most important factors the sponsor should consider when picking sites for their trial? If you want, you can even pick an example of dry eye or retinal disease. You can take this however you want it.
Amy Brown:
Yeah, there are several things to look at when they want to pick a trial site. Specifically, I think they want to look at subject population and retention, keeping those patients in the study and not having them drop out. I think research experience of the investigator is very important and geographic location. I think you just kind of touched on that. You don’t want to do a dry eye study in Texas during allergy season when subjects might be taking antihistamines. That may exclude a big part of your subject. I think that’s something to look at.
Even age, whether it be a pediatric population or a senior population. There again, I don’t think you really want to do a study in Florida with senior citizens who may be spending 6 months in Florida and 6 months back home and up north. Geographic location, subject population, and retention, and I think research experience for sure is very important when considering a trial site.
Andrew Pucker, OD, PhD, FAAO:
Yes. I think research experience is absolutely huge. We want to, of course, have some new researchers in the mix too, but I like to always, when I’m talking to sites, you want to be honest with us. If you think you can get 10 subjects, we need you to back that up. If you can’t do that, please say no because we may not be able to use you in the future if you kind of fall through. Have you kind of seen that too?
Amy Brown:
Oh, yes. Kim probably has seen it a little bit more than I have lately in some of her studies. Yes, I think subject retention is looking to see if that subject population for that particular site, like you said, if they don’t have the subjects, there’s no point in going through the process of getting involved in the research without having that subject population there.
Kim Williams:
Yes, knowing that very early on is ideal so that you don’t waste the site’s time and the PI’s time going through potentially local IRB all that document collection if they don’t actually have the population identified and willing to come in for a long study.
Andrew Pucker, OD, PhD, FAAO:
Yeah. I think we’ve all been on studies where a site’s like, “I can get 5,” and at the end, they can’t get any. Then everyone’s just kind of mad. Kim, kind of following up on that, when do you start thinking about site selection? You get a new protocol that sponsor signs in the contract dotted line saying, “We’re going to do this.” What do you do? Do you wait until you see how things shape up or when do you start looking at different sites?
Kim Williams:
I think if you can look during the bid defense that is ideal, you can present that as part of your bid defense. We have identified this number of sites who we’ve worked with in the past or they’ve been recommended by a monitor or even another site. They enroll quite well, their subject retention is at a certain percentage. If you can present that early, that may help with your bid defense. You may need additional sites, of course, a bit later as you’re going through startup. I would say making sure that your feasibility questionnaire is robust and asking all the right questions and ensuring that they have the equipment they’ll need if that’s a big purchase, maybe a -80 freezer, that this may not be the site for you, that can be quite expensive. You just want to make sure that as early as possible, you’re picking the right sites.
You’re always quite often, I would say, going to have to add sites later in a study and then you want to use your experience with your first sites to determine the next 5 sites that you need to add, ask the right questions.
Andrew Pucker, OD, PhD, FAAO:
That is something that most people probably don’t know, right? We’re thinking about sites before we even get the project. We’re doing what we call feasibility, seeing if they have the right things we need for them to have at their site to include them. I guess it’s good to always network and be on the top of mind even before things happen, right?
Kim Williams:
Yes. Keeping in mind, if an investigator always goes to Greece in the summer, you’ll have that documented someplace so that you know maybe that’s not the right site to reach out to if you have a summer project.
Andrew Pucker, OD, PhD, FAAO:
Is that something you would capture in site feasibility? Go through that process because that’s where a lot of sites initially come into the study, right?
Kim Williams:
Yes. We would put together a feasibility questionnaire using the protocol. If you just have a synopsis, you’re using that to put together your feasibility questionnaire and you’re asking some basic questions about your location and site staff, how many sub-investigators you may have. We do like to ask if the investigators have some extended out of office, if that timeline will work for them. During the feasibility, we also ask if they have any other investigators they’d like to recommend.
I will say, Amy, and I’ve been on studies where we’ve used that information to select additional sites that maybe we weren’t aware that they were interested in clinical research. The feasibility questionnaire is very important in making sure that you’re checking off the equipment. And again, the correct site staff, they may be overloaded with other studies, and you don’t want them to end up short-staffed during your trial.
Andrew Pucker, OD, PhD, FAAO:
That kind of comes back to can you get these 10 subjects? You also have to think about I have another study that’s very similar to this, right? I don’t want to overlap too much.
Kim Williams:
Yes, we do want to know that.
Andrew Pucker, OD, PhD, FAAO:
Amy, do you think it’s important to have more than 1 PI at a site? When would you care about that? Maybe a PI and a sub-investigator under them, or how do you consider that when you’re looking at sites?
Amy Brown:
I think having sub-investigators are very important, specifically going back to something Kim said, and if an investigator has some out-of-office time, it would be nice to have a sub-investigator who is well qualified for the study and trained under the PI to step into that role. It’s not necessary, but it certainly does help. That’s something that in the feasibility that we make sure that we note that there are a sub-investigator or other sub-investigators as well as study coordinators. That’s something we also want to know, is there a backup study coordinator? If the primary study coordinator is also going to be out or sick, is there somebody else to step into that role?
All these questions that we ask during feasibility play a factor into how we as a CRO will identify a site and present it to the sponsor but also get the sponsor’s approval. I think sponsors do like having other people who are qualified to run a study if the primary investigator or primary study coordinator needs to be out for any reason.
Andrew Pucker, OD, PhD, FAAO:
It probably is also important, say you have a masked study, and you need to have a masked and unmasked investigator. I think you’re saying, having more than 1 clinician at the site is beneficial if you can make it work.
Amy Brown:
Oh, absolutely. That’s a very good point. Anytime you have a mass study, you do need another person, another set of eyes, so to speak, to be there in order to make sure that everything stays confidential and taken care of by the people doing that particular role.
Andrew Pucker, OD, PhD, FAAO:
You have a finite number of sites, and it sounds like people eventually retire, which is why we want to have more than 1 doctor at a site. How do you get in as a new site? Say you’ve never done an FDA trial, would you ever consider a site like that or what would you look for to get them over the line into the mix?
Kim Williams:
Yes. We would want to get new sites on board. I think that’s when your monitor will go on site during site qualification visits. That’s when we’re looking at sites to care, you would want to make sure that that monitor is well-trained. They know exactly what to look for as far as site staff, you want to make sure they have the equipment as we mentioned and dedicated spaces for study drug or the device and also a dedicated space for the monitor. When they go on site to visit, they want to make sure they’re not just put in the break room while everyone’s eating lunch and need space to review all those records. I think that’s where monitor training and site training come in. There are cases where you may have a remote visit. I think we wouldn’t want to choose that for a brand-new site.
If that site then gets selected, your site initiation visit also needs to be quite robust, a great tour of the facility to see where all of the assessments will take place and again, very robust training and you may want to consider sending your monitor back more frequently than you would for sites that you’ve worked with for years or on many trials, just to be sure that we’re keeping up with any additional questions the site staff may have and ensuring that they are comfortable with all of the assessments and the protocol.
Andrew Pucker, OD, PhD, FAAO:
We know there’s different trial phases, right? There’s the phase 1, which is first-in-human and sometimes even the phase 2 is first-in-human, depending upon the drug. We’re working on our device as our own kind of categories, but then there’s also phase 3. If I’m a new site, do you think I’m going to be more likely on a phase 3 pivotal trial or like on the ground floor new study phase 1 sort of thing?
Amy Brown:
That’s a difficult question. I think I would have them more on a phase 1 than a phase 3, only because a phase 1 is typically a smaller study. A lot of times, when you get into phase 3, you’re getting into a large study, but that’s my opinion. I don’t know. I’m not sure we do get a lot of new sites through word of mouth as I think Kim mentioned earlier from monitors who may be visiting sites and I think we would probably listen to the monitor’s feedback on that to see where that new investigator may fit in best. Maybe it would be a phase 3.
Andrew Pucker, OD, PhD, FAAO:
I think that’s interesting. I think it can maybe go either way, it sounds like. When I asked that question, I was thinking you might say phase 3 because there’s potentially say 30 sites on a dry eye trial and if 1 doesn’t go well, well, you got 29 more, but maybe you want to have a less complex study of phase 1 for these newer sites. I guess it really depends, huh?
Amy Brown:
Yes, I think so. I mean, I think that could be a trick question too.
Andrew Pucker, OD, PhD, FAAO:
Yeah. Yeah.
Amy Brown:
It’s hard to know, but I do think feedback from other, like I said, monitors or people who’ve worked or know of these new investigators could help us in making that determination.
Andrew Pucker, OD, PhD, FAAO:
It kind of sounds like it maybe comes down to the sponsor, right? I don’t think we’ve made a clear distinction in today’s episode about where we’re at. We’re at a contract research organization and we’re working for companies that want to do studies, and I think it really comes down to the sponsor at the end decides who the sites are. Maybe Kim, you want to talk about how that interaction works?
Kim Williams:
Sure. We here at the CRO would come up with a site list again, sites we’ve worked with, sites who’ve been referred and some of those sites are referred by the sponsor. If they’ve worked with those sites in the past, they will put them on the list. We would go through the list, send out feasibility to everyone and determine who may be the best fit. We would present that site list to the sponsor and get approval to do the site qualification visits. That’s when our monitor would go on site and determine, again, staff, equipment, space just to ensure that the site meets all of those requirements. At that point we send our recommendations back to the sponsor. Now it’s possible to approve all sites and we may not need them all. Then we have to come down to who can enroll the most in the time that we’re expecting.
We like to keep a good site relationship. Sometimes that can be hard when you’re only selecting some of the sites that you’ve evaluated and at that point we would move on to the site initiation visit and that’s where the training comes in.
Andrew Pucker, OD, PhD, FAAO:
I think it’s sometimes really hard at the CRO. We have these great sites, we want to include them and maybe there’s only 100 subjects to recruit, so we can only select say 5 sites and that’s good, bad. We get done fast, but at the same time, we don’t get to include some of the sites we’d love to include. Amy, I have a question for you. We have this list of sites. What are some red flags that would prevent you from even bringing these people to a sponsor?
Amy Brown:
I think Kim alluded to some of this a little earlier. We want to make sure they have dedicated staff and not only dedicated but qualified and consistent. We want to make sure that the staff that’s there has been there a while and understand research. That would be a red flag if you didn’t have a consistent study coordinator. We also want to make sure that we have a dedicated research space, especially for study specific assessments and also a secure area for your study product. We want to make sure that it’s in lockdown, people aren’t just going to be able to open up a refrigerator and mess with any of the study product that may be in there. We also want to make sure that the investigator is making time for the study. I think that was alluded to back with feasibility. If they have other studies that are ongoing, are they going to be able to dedicate time to this particular sponsor study?
If they’re not making time, that’s a red flag. Sometimes not having the equipment could be a red flag. It depends on the sponsor and whether they’re willing to help that site acquire the equipment and pay for it. There are certain things that we are looking for to make sure of, but I think having a very consistent, qualified, dedicated research staff is pretty important.
Andrew Pucker, OD, PhD, FAAO:
Yeah. The people are the backbone, right?
Amy Brown:
Yes. Yes.
Andrew Pucker, OD, PhD, FAAO:
Okay. Kim, I know you’ve been involved with developing some new technology at Mintra. What have you seen in ophthalmology trials that are as new related to technology that you think could make things more efficient?
Kim Williams:
We have tried to implement in our studies more of an electronic source document. I think most ophthalmology sites that we’ve worked with in the past are still quite paper-based. That has been new for ophthalmology and there’s been a little pushback on the adoption of the electronic source, but I think as more sites get accustomed to using it and find that it’s actually saving them time, I think more and more sites are going to be willing to adopt that. They’ll find that, of course, it’ll save a lot of space in their practice and it’s much more of a real-time entry versus going back and having to sign source documents.
I think that has been something that we are implementing here at Mintra, and site’s willingness to use e-binders as well. That’s something that, again, a lot of ophthalmology practices may be compared to some therapeutic areas, they’re still very paper-based, but we’re trying to get them more accustomed to using electronic binders. Things go out of date, you get a new protocol, which can be 170 pages. The site needs to print a new protocol for their binder versus having an electronic version of that. I think those are the things that sites are realizing they can go in and grab the most recent log electronically versus being at risk of picking the wrong paper log that you’ve printed a template in your binder. Those are things I think that they are adopting as they see that they’re much more useful for their daily practice.
Andrew Pucker, OD, PhD, FAAO:
I really love the idea of getting rid of paper. If we think of some of our sites, they’ve done over 300 trials, right? Can you imagine having 300 plus study binders plus all the stuff that goes along with the study just hanging out in a, I don’t know, a storage unit.
Kim Williams:
Right. It’s a lot of paper and it goes offsite and then when you need that document 5 years later in its offsite facility, someone has to go and collect that. It would be much easier and faster if it were just electronic.
Andrew Pucker, OD, PhD, FAAO:
I always think of my master’s thesis. I had a stack of about 200 peer-reviewed articles printed off. This is back 15-plus years ago and I had to find a specific paper and dig through that stack sucked. After I finished my master’s, I just recycled all that, went 100% electronic and I basically don’t even use a pen anymore. Amy, a while ago, you mentioned that geographic area matters a lot. Some studies we work on are international. What would you consider if you wanted to bring your study to multiple countries versus just in the United States?
Amy Brown:
Actually, I’m going to let Kim take this because she’s actually working on doing that, and I think she probably has expertise way more so than I do.
Kim Williams:
Yeah. We are looking at opening a site in Latin America working on a rare disease right now. Those patients are harder to find. You want to make sure that you’re working with a good CRO in the country that you’re trying to open a site in and make sure you meet all of those regulatory requirements for that country. You also want to make sure that your sponsor is ready and willing to pay for any travel. Traveling either from another country to a site in the US that can get quite expensive. But again, if you have a rare disease, it is worth it in the end for your study.
They also, especially in ophthalmology, they’re likely going to need a caregiver. You want to make sure you’re covering the cost of caregiver as well and for extended stays. Some of these subjects, if they’re coming from another country to the US for some of the visits, they are not going to travel back home between day seven and day 14.
They’re going to stay for that extended amount of time. Then you’re possibly going to transfer them back to their home country and for all of those subsequent visits. You just want to make sure that you have a way to track their progress and their visits and images that you want transferred over for the study, put into certain portals, if you will. I think being able to go into another country where these subjects may be interested in trials that they’ve not been able to participate in the past, I think that can really help your study if the funds are available to open a site in another country. We understand that’s not how it always is, but yeah.
Andrew Pucker, OD, PhD, FAAO:
There’s a couple of ways you could go about this. You have a rare condition potentially and they’re just scattered around the world, but there’s only like 1 or 2 in each country, as an example, just an example. Then you might fly them to your main site in the United States, right? It’s one option, or you might actually run a full onsite in another country, right?
Kim Williams:
Yes. I think all those options are great. You want to consider any option that will help you find the patients that you need. I mean, you’re helping those patients who, again, if there are only 2 subjects with a rare condition in one country, not all sponsors are going to open a site for that. Being willing to pay for their transportation to the main site, I think is huge.
Andrew Pucker, OD, PhD, FAAO:
It sounds like it’s a lot cheaper to fly one subject to the United States for a visit rather than open a whole site for 1 subject in another country.
Kim Williams:
Yes. If you have a population in that country, then you want to look into opening a site in that country, but you still may only get 4 subjects, something to consider. But those 4, if it’s a rare disease, they’re important to the study.
Andrew Pucker, OD, PhD, FAAO:
Yeah. Some studies might only need 10 total subjects, right? That could be 40% of your cohort. Kim, if you had to give 1 piece of advice to a sponsor starting up an ophthalmology clinical trial, what would you give as that advice?
Kim Williams:
I think being realistic and reasonable with your expectations, whether that’s timing, enrollment, or just site’s willingness to focus only on your study. Sites often have many studies, and they can’t necessarily dedicate someone to your study 100%. Being realistic and reasonable, maintaining site relationships is, I think, the biggest thing that we focus on here at the CRO. It’s great if the sponsor is backing us to maintain a site relationship. We work with these sites and they help us, we help them. What we don’t want is to push them too hard and then they think, “This is too much hassle. I don’t want to do this again.” I think site relationships and being reasonable with your expectations is my number one takeaway.
Andrew Pucker, OD, PhD, FAAO:
That’s great. Amy, do you have any other tidbits to add, take away?
Amy Brown:
I completely agree with Kim on that, treating the sites fairly and maintaining great relationships with those sites because you never know, they may want to do another study, and you may want that site back in your study. I also think that if you treat them well, they’re going to do good work for you. I think that you could expect good results from a site if you treat them fairly and put forth those reasonable expectations on the sites and staff like Kim just said.
Andrew Pucker, OD, PhD, FAAO:
That’s great. With that, I’d like to thank our guests, Kim and Amy, for joining us on the podcast today.
Amy Brown:
Great. Thank you for having me. It was lots of fun. It was a good conversation, and I hope listeners get a lot of value from this.
Kim Williams:
Yes. I’m always excited to reunite with Amy and be on an exciting podcast.
Amy Brown:
That was fun.
Andrew Pucker, OD, PhD, FAAO:
That’s great. I would like to also thank you for joining us today on Clinical Trials Spotlight. If you enjoyed today’s episode, be sure to subscribe and share the podcast with colleagues and others passionate about advancing ophthalmology, research, and patient care. Thanks again for listening. We’ll see you next time.
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