Incorporating Clinical Trials into Your Practice

Walt: Hi, welcome to Dry Eye Coach podcast. My name is Walt Whitley. Today we’re going to talk about ways for practices to start running dry eye trials. Clinical research is a critical element to improving the options and solutions available for patients. For some practices, there are so many unknowns and question mark they don’t know how to get involved or where to start. Today we will be chatting with George Ousler a Senior Vice President of Anterior Segment at Ora, an ophthalmic CRO about the considerations and benefits of incorporating clinical trials into your practice. Welcome George, and tell us about Ora. 

George: Hi Walt. Thank you so much for having us on your podcast. Ora is a full service global CRO, that’s been dedicated specifically to ophthalmology for more than 40 years. We’re headquartered in the United States, but have offices in Europe, Asia, and Australia. We’ve had the honor to help our clients earn 45 approvals over those years across various indications. We’ve also really specialized in the area of dry eye disease in these past 20 years, and have had the honor to see this syndication, this field evolve over time. Both in our understanding of dry eye, as well as the various products that are being developed. 

We’ve also had the opportunity to work on most of the products that are approved and many of the products that are in the pipeline. We actually have over 100 research members or staff dedicated to just dry eye trials themselves. So it’s been really wonderful to see this area of dry eye research and product development evolve. We’ve had a wonderful opportunity to work with many small startup companies, as well as large global pharma companies. So we’re very excited to share our thoughts today. 

Walt: So glad you’re here. I mean, I love doing dry eye research. We’ve worked with you in the past. I do have some sort of a questions for you. So the first question is in the midst of the challenges we all face with the pandemic, dry eye research seems to be going strong these days. What is your assessment of the current dry landscape? 

George: So you’re absolutely correct Walt, dry research has never been a busier. In fact, we’re calling it the golden era of dry eye research in our learnings about dry eye itself, but also in product development. So in addition to the approved products that we have such as Restasis, Xiidra, Cequal, and others, and more recent approvals, such as the Kala product that has loteprednol for the short treatment of short-term treatment of dry eye signs and symptoms. There’s a very healthy pipeline and a lot of innovation that’s being looked at. 

I would say that beyond anti-inflammatories, there’s also wound healing therapies, there’re hormonal therapies, very interesting devices targeted to treat dry eye. Also, some really interesting and new delivery mechanisms. So we’ve seen novel vehicles that help with delivering medications to the ocular surface, better penetration, better dwell time. But also unique approaches where we deliver medication up the nose. So nasal sprays and even subcutaneous injections. But overall dry eye is very busy. There’s a lot of phase threes that are underway, and also a lot of phase twos. Which suggests a lot of innovation and a lot of future products. 

Walt: I totally agree. People may have heard me say before dry eye is a hot topic and it is. I mean in all facets. Especially when it comes to clinical research and some of the technologies and innovation that’ll be soon on the market. One of the things you just mentioned is drug delivery. That has definitely been changing the way that we treat our patients, the efficacy, the safety, the ability for the drugs to penetrate into the eye and address the signs and symptoms that patients are having. So I couldn’t agree more. So my next question is for practices with have never participated in Dry Eye Clinical trials, why should they consider doing so? 

George: Well, I think first and foremost, we do have products available to treat and address dry eye, but it’s still a considerable unmet medical need. I feel that there are additional improvements to look at faster onset of action of products. Products that are maybe more comfortable with fewer adverse events. Possibly broader acting therapies that hit multiple signs and symptoms. So I think one of the key features here is we need to bring more therapies to market. What a wonderful way for a practice to participate in the latest and greatest science to help their patients. Also, we are seeing this approach where really it’s a poly-pharmacy treatment to dry eye. That dry patients may have more than one Ireland underlying cause or etiology. We see that dry as much more complex than one may believe. Because of that complexity, a patient may be on more than one therapy. So they may be on a longer-term anti-inflammatory combined with a shorter acting treatment for the acute signs and symptoms of dry eyes. 

So again, we need to bring more therapies to have more options for our patients. Beyond that, and I think really just being on the cutting edge. The practices that we work with in the sites really enjoyed letting their patients know that they’re involved in clinical research, that they are contributing to developing medications and providing the latest medical care for their patients. Lastly Walt, even just the concept of alternatives in the additional source of income. Clinical research does provide that stream of income for practice as well. 

Walt: So being involved with the clinical research, people have asked me what do I like about it? It’s a lot of those things that you just mentioned. We have a lot of patients, they love to be a part of the Dry Eye Clinical trials. So they’re in one study and then when it’s done they’re like, “Hey, when can I start the next one?” They do understand how they‘re helping to benefit that science and future patients, and products are going to be able to address the signs and symptoms that they have. For me, it’s just one of these things. It just helps me grow as a clinician. I get to learn about all this, this innovation when it comes into the space and drug development. So it’s been a great part of our practice. So what are the key factors to consider when becoming a site for clinical research in dry eye? 

George: First and foremost, it’s really critical to understand your patient database. So recognizing the different indications and whether it’s dry patients, allergy, patients, glaucoma patients, back of the eye retinal conditions, and really getting a good sense of what is the characterization of those patients. So often what we see in clinical research in specifically in dry eye, we become more and more selective of the patient population to be able to demonstrate efficacy. This is really coming from the fact that again, it’s a multifactorial disease with a number of underlying etiologies. So we narrow down the appropriate patient or what we call the right patient, who has the best chance to respond to an investigational therapy. So it’s very important to be able to say, “This patient has a Schirmer’s score of less than 10 millimeters. This patient has SPK or superficial punctate keratitis to this level. This patient may have symptoms to this level on the following quality of life questionnaire, or scale in general.” 

So, characterizing your patients is very helpful because when you participate in the clinical research, we want to get a good sense of how many patients will actually need qualification for that specific protocol. So I think that’s a very helpful thing to do in a practice setting. Also, whatever can be done to standardize the assessments in a clinical practice and going through medical charts. What I mean by this is maybe there is a scale that evaluates corneal staining that can be incorporated into your practice and collect the information in a very standardized way. Or use scales again, to identify symptoms in a controlled manner. This also helps with characterizing your patients. 

Also, I think having a good dedicated site coordinator is, is essential. This individual can help with working with a CRO or working directly with a sponsor. Also, having principal investigators and sub-investigators that are interested in research that can dedicate some of their time to their clinical research. All of that infrastructure ultimately will make a clinical practice successful in doing research. Lastly, I would mention that it’s really also important to think about how clinical research can be integrated into your practice, into the workflow of your practice. Some sites that we work with decide to do research on the weekends, so that it doesn’t interfere with the day-to-day practice. Other practices really like to integrate research patients into their everyday clinical practice patients. So that’s something to consider so that you don’t interrupt your core business or clinical practice. 

Walt: In our practice we just incorporate it within our clinic itself. We’re fortunate, you mentioned the importance of having a study coordinator and we have a whole team. So we have three people at our practice that help coordinate the various studies that we have. You mentioned, knowing your numbers and knowing your patient base. Just like anything, you have to track it. It’s not going to improve, but if you don’t track it, you won’t be able to deliver the numbers to the various pharmaceutical companies, or the CROs to say, “Hey, I want to be a part of clinical research. I guess a question for you is, when you try to identify a clinical site, are you looking at solo practitioners? Or do they have to be group practices? Or can you comment on that? 

George: Sure. Quite frankly, all of the above Walt, it can be any, any mix. It can be a sole practitioner. It can be a large group. Often its private practices, but we do also work with institutions in hospital settings. A lot of it is driven by what patient population we’re interested in. But at the end of the day, if the practice has sufficient number of patients again that are well-characterized, we can really work with most any group. 

Walt: So next question, what can a practice expect after they agree to participate as a site in a clinical trial? 

George: Great question. So typically a site would be working directly with a CRO on a research project. Sometimes they’ll work directly with the sponsor, but more often than not, it’s directly with the CRO. Some of the initial steps are that the CRO will lay out the expectations, the goals of the research program. As you indicated Walt, the expected number of patients, overall timelines, get through the contractual phase. Then it turns from there into a whole series of evaluations. So typically the CRO would send out a team that would do a site evaluation. That really includes things like just making sure there’re sufficient instruments and proper areas for patients to be seen, and all the right licenses and these things. Then beyond that, we go through initiation visits. So to train the sites on the specific study protocol, and evaluations, and the medication that’s being studied. So quite a bit of extensive training. 

Then, we get into the actual study itself. Through that process and the study conduct the site will work with monitors. Monitors will come out, and they’re the individuals that will review all the study data. And just to make sure that the data is clear, that we’re capturing what we were hoping to capture. And just make sure that all the information is being put into the system according to timelines. Again, just maintain the quality of the program. After that, we get typically towards the end of the study, where we’ll start to clean up the database. So the information across many sites, and some programs will have two or three sites involved. Others may have a hundred sites involved. 

So that can be a very large undertaking. But it’s critical to make sure all the clinical data that we collected both objective and subjective is clean in the database, so we can have a good understanding of the results. After that, hopefully the study’s successful. If it is then sites may undergo audits by sponsors and possibly even the FDA, if that drug looks like it has a good chance of being approved. So many different levels, but this is something that an experienced CRO would certainly work with the site, and share their experience, and hold their hands through the whole process. 

Walt: Well, you pretty much answered my next question that I had for you is, what are the benefits in partnering with a CRO audit clinical on a dry eye trial? Is there anything else that comes to mind on that? 

George: Well, I guess I could say a few words around Ora as a CRO, especially in the area of dry eye. So working with someone like us, we’ve got an extensive history in dry eye, and if that is the indication of interest. So we often partner and collaborate with sites. Something that we do that’s unique is we can help to provide resources to sites. So some sites that may be interested in research but don’t have the appropriate infrastructure quite yet, we have certain situations where Ora can help to provide coordinators for sites. Often we can help with recruiting patients and running advertisements for that site. We also have a unique model where we may clinical staff to help see the patients for the research study. Of course that would be under the delegation of the principal investigator at that location. But that really helps sites get involved in clinical research and it makes it very efficient. So you can see larger number of patients in shorter periods of time and have some really dedicated resources. 

Beyond that I think just establishing long-term relationships with sites and CROs is also key. That ultimately leads to a pipeline of studies. As you indicated, Walt, not only are your sites excited about next studies but also patients. So that’s something we’ve certainly seen. A final comment is there’s also a lot of innovation that’s happening in quantum research beyond the actual study drugs themselves. This is an area that ORA shines quite a bit, where we have different technologies to help with patient enrichment and helping with really trying to standardize end points, and try to minimize what we call the background noise. So there’re different technologies that Ora may use with the clinical research that we bring to a site to help them conduct that research. So we have some mobile laboratories that pull up to your practice and contain some of these technologies, which is fun and exciting for the sites and the patients. But I think it’s important to be involved with a CRO that can really help us site develop. 

Walt: Yeah, I’ve been involved with that mobile truck before and it’s very interesting. It’s exciting for the patients and us as well. We know how trials positively impact the industry, but how do these dry trials positively impact the practices involved? 

George: Again, I think it’s really to help these practices bring additional therapies to market, being part of that cutting edge. We work with sites that will put out a lot of material that they are involved in clinical research that they’ve contributed to the latest approval. That goes a long way with their patient database, and really just expanding these treatment options. I would say too that again, it is a bit of an additional source of income for a practice as well. 

Walt: Mm-hmm. One of the things you hit on is it’s a differentiator for your practice. It’s offerings that you’re able to give our patients and your patients. Many patients, I mentioned that love to be part of the trials. But then there’s also some patients that we give them all their options, “Hey, we can prescribe this or we can provide that. But you’re going to be a great candidate, we’re doing this clinical research trial. Are you interested?” “Yeah, I’m interested in tell me more.” If it works out for them, it’s great for the patient and great for us as well. So let’s talk about publishing the clinical trial results in peer review publication. Can a practice or an investigator be involved with this? 

George: Definitely Walt. In fact, sponsors are very excited and often request sites to be co-authors on publications. They tend to publish early stage studies, so phase two studies, as well as the later stage phase three registration programs. Clearly it’s the principal investigators, the sub-investigators at clinical sites that are conducting the research, and it’s most appropriate to have them present that research. So that is very common. I know a lot of sites get excited about this. In fact, we’re talking about demonstrating to your patients in your local community that you’re involved in cutting-edge science. This is something that’s been nice to share with patients in the community is published papers by investigators in that trial. So, yeah I think it’s wonderful. We’ve actually seen that also practitioners are asked to give presentations locally and also at national and international meetings as well. Having again, conducted the research and sharing their experience in that process. 

Walt: So are there some recent completed trials that you can talk about? 

George: Wow! We can talk about a lot of things, Walt- 

Walt: Which one? Is that what youre saying? 

George: Well, like I was saying earlier Ora, is heavily involved in dry eye and we’re running the majority of phase two, phase two programs out there. We’ve had the honor to do this over many, many years. So we could talk way into the evening about this. But what I would say is that there’s a lot of phase threes underway. Which means that this is going to turn into a number of approvals. We’re hopeful that within the next, I’d say two to three years, we’ll see more therapies and options being brought to market. But additionally, phase two programs are also very nice to see. That basically is planting the seed for the future, for next generation dry eye therapies. What’s so exciting about this is as we talked about in the beginning, there’s a lot of different therapeutic approaches. There’s novel delivery mechanisms, there’s very novel APIs. A lot of very out of the box, really interesting approaches to treating dry eye. So, we see a very healthy pipeline in the long term. 

But what I would mention Walt is, as far as a more recently completed program is a company called Oyster Point. They have a very interesting therapeutic approach to treating dry eye. This is the company that has implemented a nasal spray that delivers an inactive treatment up the nostril, basically to interact with the trigeminal nerves. That ultimately results in tear production. So it increases tear production quite significantly and also, reduces the symptomatology of dry eye. What was so interesting about this program is they’ve run just a couple of studies and they’ve been able to demonstrate… and they’ve met pre-specified primary end points. So it’s probably been one of the fastest dry eye programs that we’ve ever seen. If you look through the press releases, they’ve indicated that we’ll be submitting an NDA by the end of this year. Which is very exciting. So that’s probably the latest and greatest Walt, and a very effective therapy with the unique and interesting delivery mechanism. 

Walt: Yeah. Targeted therapy. Whether it’s going to be through the nasal cavity, whether it’s the drops. Kind of like MIGS technology. When it comes to glaucoma, there’s a various devices that can target the various… Whether it’s going to be the production, whether it’s going to be the drainage to the trabecular meshwork, or subcutaneous space. But now we’re doing this with dry eye with various target therapy. So it’s definitely is exciting. So my last question for you is you’ve shared all this great information, so how does someone get started? Who do they need to reach out to? 

George: Great question. So certainly reach out to Ora. We have our website oraclinical.com. There’s actually a site on [inaudible] on our site for investigators to express interest. Certainly you can give us a call at the organization as well. There’s also emailing contact information on the website. But we’re always happy to speak to sites and explore opportunities. Like I said, there’s no shortage of dry eye studies, which means that there’s a huge need for additional investigators and sites to get involved. As mentioned before, Ora really likes to establish long-term relationships with our sites. Possibly start with dry eye, but get into ocular allergy, glaucoma therapies, retinal disease, medical devices, so on and so forth. So yeah, we absolutely look forward to hearing from everyone but be happy to engage in some exciting discussions. 

Walt: George, you said there’s no shortage in dry eye studies. There’s no shortage in dry eye patients either because we know that there definitely is the need for patients. But I do want to thank you so much for taking the time. It was great to have you. George Ousleronce again, senior vice president of Anterior Segment from Ora. So thank you all for attending this podcast and we look forward for you to listen to our next one coming up. So thank you all very much and have a good one. 

George: Excellent. Thank you. 

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