This live webinar will discuss performing clinical trials in an ophthalmic practice. Presented in this talk will be a brief overview of the global perspective of clinical trials occurring around the world, the benefits of conducting clinical trials and why you might want to consider doing clinical trials, and a review of what is needed to establish clinical trials in your practice or ophthalmic setting.
Lecturer: Dr. Jason Chin, OD, FAAO, Boston, USA
Initially, I was a little hesitant about presenting this. I didn’t think there would be that much interest. This was pre-COVID. Now that we all have something in common, it doesn’t matter which part of the world we’re in, we’re all dealing with the pandemic and a worldwide situation. In some aspect, COVID has affected all of us in our countries. With that, there is the interest of: Can we find a vaccine? Can we find a successful treatment? And what that involved is clinical trials. So that’s why I decided I think this might be very useful, as we all have that as a topic in our daily activities. Now, we’re not all gonna be directly involved in actual COVID. And finding the vaccine or cure — many of our countries are already successfully underway — this isn’t gonna be part of that talk. But the clinical trials aspect is something that we could all possibly potentially get more involved in, if that’s something that has piqued our interest. The other thing with a lot of these Cybersight talks is looking at ways of how we can treat our patients and benefit our patients. And I think a lot of our thought process is: All right. I’ve got something going on. And I can treat it. They’ve got a refractive error. How do I get it so they can see clearly? They’ve got cataracts. What can I successfully do to remove the cataracts? There’s always a direct correlation. But one of the things I also thought about is: That with clinical trials, we are indirectly improving the lives of our patients. That may not be a face-to-face, but any contributions that we have to the clinical field is something that may help either our patient or one of our colleagues’ patients. So that’s where this talk stems from. So let me bring up my slide. So everybody should be seeing my screen. Let me know if there’s something you can’t see. So the topic today is conducting clinical trials in the ophthalmic setting. I’m a principal investigator for Andover Research Center in Andover, Mass, I’m also a clinical investigator and consultant for ORA, and that’s where the majority of my experience for this talk is stemming from, and I’m also an optometrist in Andover, Massachusetts, based in the US. We do have offices located in the UK, Japan, and China. We are a worldwide company. So any information you may find useful isn’t just local. I usually base it off a US-based audience. And part of this talk was to basically open up a means of revenue stream for the optometrists, where here in the US the third party system is hindering our revenues that we generate. But this talk can basically be structured for anywhere in the United States. There might be certain regulatory differences, there might be some financial differences, but the clinical trial aspect works whether you’re here in the US or anywhere else in the world. So here’s what I’m hoping to accomplish. I hope to show you how to incorporate clinical trials into an ophthalmic practice. Now, again, there’s a lot of aspects and a lot of fine details that I will not have time to go into. And I apologize if I do kind of — for the interests of time — skip over some of these slides. These slides will be available afterwards. So if you have any other questions, or something you want me to discuss more in detail, either in the Q and A session, or even a separate email, I’ll be more than happy to try to see how I can answer any questions more specific to your setting. But for today, it’ll just be kind of a more global general sense of an ophthalmic practice. I hope to show you how bringing clinical trials can benefit your practice, and I want to hopefully show you what you need to think about, if you want to actually incorporate it. So I guess I’m not gonna be going into the nitty-gritty about a specific clinical trial. But if you’re thinking: I want to do a myopia control study, a drug study, a treatment study, it all encompasses the same thing and the same thought process. So why would I want to do clinical trials in my practice? Let’s throw up a poll question first. Lawrence, if you want to throw up question number one… So do you currently do clinical trials in your practice setting? All right. So waiting for the results to show, see how many of us actually do it. All right. So it looks like a fair amount of you do it, but the majority of you either have not or would like to do it. Good. We have a good audience here for what this talk is about. So why would I want to do clinical trials in my practice? So the first thing I wanted was to kind of get a global overview. Since we are in different situations. How would clinical trials go on around the world? So these numbers are pre-COVID. The numbers may have skewed a little more, depending on how aggressive a country or region is, in trying to find a vaccine or a cure, but generally 42% of all clinical trials going on. Now, these are just in general. Not just ophthalmic clinical trials, but overall, 42% are going on in the US, about 20% in Europe, 10% in East Asia, and the rest fall in different regions of the world. So how might this benefit me and my practice? Well, basically, one of the main things — I wanted to introduce clinical trials. As doctors, as clinicians, we all have that in the back of your brain. But I wanted to introduce it more as a possible new revenue source. Again, depending on where you are, your income may be fixed by patient. You may not be able to differentiate one patient from another. But for those of us here in the United States, by doing a clinical trial, we can control a little more of that revenue stream. So we can get income from an outside corporate sponsor. We also can have more control of the patient reimbursement. We can dictate whether we are going to get reimbursed for our chair time, versus third party reimbursement, which may say: You see a patient, doesn’t matter if you spend 10 minutes on it or half an hour. You’ll get the same amount. You have more control of your profit margin and chair utilization. Because this is different, I’m not gonna spend a whole lot of time on that. But in general, it is also a practice builder. This may be a way of doing something in your practice that is going to bring patients that you may not have already seen into the practice. It gives your practice an extra-competitive edge. So if you have a therapy or treatment that is brand-new, you may be able to say… Hey, based on my competition, they cannot offer it. This is something I can offer if you want to come in to do a clinical trial. It might bring new technology into your practice. So you maybe have an opportunity to try a piece of technology, a machine, that would otherwise be unavailable to you, or your region, by doing a clinical trial. That’s another way to contribute to our field. A lot of times as doctors, we’re thinking about patient A, and what do we do for patient A. But in this aspect, you may be generating information that will help your colleagues to cure their patient A, patient B, and patient C. So indirectly, you will be helping more patients by bringing out useful information. And it can take you out of the rut of the normal, everyday routine. For me, this is one of the things — why I like doing clinical trials. Monday through Friday, and even Saturday, sometimes we’re just doing the same thing over and over. Ophthalmologists, where you have a surgery mixed in with it, you do have that kind of break in your week, break in what you’re normally doing. But sometimes for the optometrists, we just do the same thing, in and out. Routine exam. A contact lens fit. Maybe treating something here and there. But it’s the same sometimes mundane situation. So by doing a clinical trial, optometrists — we can’t do the surgery. But we can now do something else that is something totally different than our usual day-to-day routine. So how do I actually get started into doing clinical research? And one of the questions here that I had earlier is actually asking that. Oh, so one of the things I was gonna mention. So one of the particular questions that I had before, that you guys submitted earlier, was: What exactly is clinical trials? Sorry about that, but clinical trials is basically the means of conducting a test or research with patients to gather more information on a treatment, a therapy, a procedure, something like that. So to answer the person who asked about that, that’s what clinical trials are. So there are a couple of things that we need to look at, before we know whether clinical trials are going to be appropriate in our situation. So the first thing we want to consider is: We are gonna do a clinical trial. What kind of clinical trial do you want to perform? So there are various different types. There’s gonna be a comparative trial, marketing trials, and even new product/technique/treatment trials. One of the questions I got earlier was: What might be the best way to get into clinical trials? That would be looking at the type of study. And usually what I find is a comparative or marketing study is gonna be probably the easiest way to kind of get your feet wet. Again, my specialty is contact lenses. So a comparator trial might be: I’m gonna take contact lens A and I’m gonna take contact lens B, and I’m going to measure five aspects of it, and see if one of them works a little bit easier. Or a marketing trial. I want to take a product, contact lens A, and I’m going to poll 50 patients and find out what their interests are, or what they like about this. Was the vision good? Was the comfort good? So in clinical trials like that, it tends to be relatively easier to get into, because at least on the administrative side, there’s a little bit less that you need to worry about. One of the things I’ll talk about later are possible adverse events, some of the unknowns with the product. Usually with a comparative marketing trial, we know a lot about the information. We want to get more information to either present to our colleagues or to present to our patients so they can make more of an educated decision as to whether to use it. But this product is already available. When it’s not available, sometimes it can get a little bit dicey or a little bit more difficult, because now let’s say you’re trying to recruit a patient. Some patients may be reluctant to use something that is brand-new. If you can say… Oh, this has already been out on the market, plenty of people use it, again, they’re just gonna be one of those people that use it. But if it’s something new, they might be more reluctant. There are certain variables or findings that we may not expect to get. That’s part of the trial. We’re looking to see if we have outliers. Does this treatment cause certain side effects? That’s how we get the information. You will have to deal with that a little more. And again, being new at clinical trials sometimes can be a little more intimidating, but as you do it more, it becomes second nature and easier to say this makes sense, this doesn’t make sense. So how big a study do you want to conduct? You need to know how many patients to enroll to demonstrate clinically significant results, does your practice have the patient base to accomplish your goals? And do you currently have an easy database to recruit subjects from? How do we determine what that number is? Sometimes you don’t have to determine that number. If you’re working with a corporate sponsor or as part of a study group, you’re one of many sites. Sometimes you don’t even have to figure that out. It just may be… We want you to do it. We need you to bring in 50 patients. The rationale behind that might be a statistical significance, but it might not be something you need to determine. If this is a self-study that you’re doing, then yeah, maybe you might have to come up with a rationale of why you want to do it. Another question was: Do I need to have a statistician? Not necessarily. Again, if you’re working with a CRO, which I’ll go into detail what that is, or a group, they may already be crunching numbers for you, so you don’t have to worry about that. But again, if this is a study that you’re self-funding, or you’re starting up from scratch in your own… Yeah, the help of a statistician might be useful if you are trying to show statistical significance. If you’re just trying to show: Oh, I’ve got a product here, and 9 out of 10 patients were successful with it, which is maybe — you’re doing this study as a precursor to lead into a much bigger one, to show statistical significance, the importance of a statistician may not be as important. So… Do I have the proper equipment? Do I have the proper space? Do I have the proper timing and funding? So all these are little things that you need to think about, because you will be doing something different. So if you normally have your practice setting, if you only have two lanes, do you have an extra lane to bring in extra patients to do it on a study visit? Do you have enough staffing to actually work up these patients, to get them through? Do you have enough time? You might be in a busy clinic, and Monday through Friday, 9 to 5, you’re seeing patients. You may already be maximizing your schedule already. You might not have the time to do this in addition. So it might involve maybe working on the weekends, or adding extra hours at the end. Do you have personal time to sacrifice that? Does the practice have time to sacrifice that? I won’t say sacrifice, but to add that into the general routine. Equipment. So there might be some aspects that we need to look at things. I know I had another question here, regarding doing clinical trials in a mobile setting, so that you can use different… I guess villages or tribes is maybe what the person was alluding to. So you can increase your patient base, or if you’re in a more remote area, yes, you might have to go to them. So do you have the equipment that allows you to do that? And do you have the funding? You know, there is gonna be extra cost, initially, to do this. Now, again, when I initially developed this talk, the whole purpose of this was to say: Yes, you can do this to generate extra revenue or profit. But just like any investment, there is gonna be a little bit of funding that you need at the startup, to either generate advertisement, perhaps get a new piece of equipment to run the study, you do have to reimburse patients before you get paid for by your sponsor. So all these little things, you just need to make sure you have that available to you. Will you be the investigator, or will you be the co- or subinvestigator? The investigator is the lead doctors who are in charge of the study. And as a subinvestigator, you do not have quite the same responsibilities. You might have all the same tasks as the principal investigator, but ultimately thinking of the whole system as the orchestra, the principal investigator is the conductor, and you may be one of the players that are watching or listening, and might have an important role in this team to investigate everything. Are there any obstacles that you might encounter? In particular, when I’m talking to a very global population, we all live in different countries. We all have different government regulations. Is there anything that is going to prevent us on a federal, government level, from doing clinical trials? Is this something where the government has to control what it is? Or just something where you can do whatever you want. You just need to make sure you follow the proper checks and balances and report to proper government regulations. Are there location issues? The person I referred to earlier. If they might be in a more remote location. Can you be stationary and bring the patients in? Or might you have to consider going to different regions, to different sites, to get the population that you need. Are there any cultural diversities of population? Is there something about the culture in your country that might make doing clinical trials something that is not highly looked upon? It is taboo or not a good thing to be testing something on your eyes? Or to be using a product that has not been used on other people. So finding the population might make it — you might want to do the clinical trial, but if you can’t find the population to do it, it might make things a little difficult. Sociodiversity. Are there certain aspects of your region that might make things a little more difficult? Where I find that doing clinical research in lower economic — places where there’s a lower status of economics, sometimes doing the clinical trials are a little bit more abundant or a little bit easier, because you do have that population that is saying… Oh, you’re doing a clinical trial. You mean if I volunteer, I can make money for it? Then they may be more willing to volunteer. Versus there are some places where we want to do clinical trials, but because of the… Status and maybe there’s more of a wealth, it may be more difficult, because now you have that population going… Well, I don’t need this extra discretionary funds. I don’t need to volunteer. They may be less likely to be willing to do that. Something you need to take into consideration. And the general environment. Is there anything that might make things a little more confounding? One of the things we do are a lot of dry eye studies. And there are certain means of protocol. So we would think that… If we were doing a dry eye study, we might find more dry eye patients in a drier situation. Which very well could be true. But sometimes based on what the sponsor is looking for in the protocol, you might actually not be able to use too dry of a patient. So if your environment is causing everybody to come in as dry eye but they’re not meeting inclusion criteria, that might make it more difficult, where we want run-of-the-mill, the normal patients, in a normal environment, that do have dry eyes. So you have to look at stuff like that. So we’ll talk about the aspects of… If I want to do it, what do I need to consider? We also discussed — there’s a little bit of monetary incentive to it. So if I am going to be making money off it, who is paying for this? Usually in the bigger clinical trials, when we list it on the news, we hear about the COVID-19 vaccine trials, and we have some volunteers, there’s probably gonna be — someone has to back it. In this particular case in the United States, we have Pfizer and we have Moderna, who have the bigger names of a vaccine that’s in the United States. So they were the big ones that are supporting the clinical trials, the funding for, the staffing, and all that. But sometimes you may decide — hm. There’s a piece of information I want to find out. I’ve got a unique patient base, and there’s something interesting I want to present out there. Well, then, you might have to sponsor yourself. You might have to say… Well, I want to test this contact lens. I think it has a unique property that maybe it helps more for dry eyes. So I want to gather this information. Well, I want to do a small study. Let me do it on a 15-patient base. You might have to fund it. I might have to see this on my regular time. For the contact lens that’s been provided, I might have to purchase those and give them to patients. I might have to give a minor stipend, a little bit of monetary fund to take care of the time. That might be something to start getting the ball rolling. You might have a grant. It could be a private grant not necessarily through a corporate sponsor, but it could be like an entity — some kind of society that says… Well, we are looking at a certain type of macular degeneration, so we have a society, a private grant, that we want to give a researcher, to try to get more information about it. You could apply for that. Or it could be government funded. COVID-19. We’ve got — we need a vaccine. So the government is going to put some money into it, so that we can speed up the process or help those who can get this out sooner do what they need to do. I was talking earlier about a CRO, contract research organization. This is a company that is contracted by a bigger entity, like a company, corporate sponsor, and will be the ones reimbursing or paying for it. So the company or corporate sponsor pays the contract research organization, and the contract research organization pays the investigator. And we act kind of like that middleman or another type of conductor. We may have a particular study, but we might need 10 sites around the United States, 10 sites around the world, so we would be the ones, instead of the corporate sponsor dealing with it, we would be the ones that find those sites and bring them together, as a unit, to get the information for the clinical study. And then on a smaller unit there, there might be a site management organization, or SMO. They basically take maybe some of these global sites, and then they manage it more on a local site. So all these entities may be providing funding for your clinical trial. All right. So what else do we need to do, to get started? Well, one of the main things is… In any clinical trial, we need to know: What are we trying to accomplish? So we need a protocol to follow. So the first thing we need to do is design a study. So what we want to figure out is: What are your goals, purposes, or hypotheses for this trial? And what references do I have behind it, to say: This might work, or maybe this may not work. We need a little bit of backing, to make it relevant of what you’re doing. Do I want to try to show this contact lens works better than another contact lens? Do I want to try if this therapy is more successful than this other therapy? Now, again, if you are developing this clinical trial on your own, this question might be something you have to look into. But if you are starting off by working with either company, this question may already be answered. They’re gonna be presenting it to you. This is the question we want. We need you to help find it. That’s why you’re doing the clinical trials. You develop a protocol that will prove or disprove the theory and figure out what phase of a clinical trial. I’ll go over that in a minute. Whether you want it to be masked or unmasked, whether you want it to be crossover or non-crossover, and whether you want it to be randomized or nonrandomized. So on these other ones, masked or unmasked — do you know what the treatment is? Or are you gonna be as an investigator blinded to what the treatment is? Are you gonna have a cross over? Are you gonna — is the subject gonna have one treatment and that’s the only treatment that they’re randomized to? Or if there’s two or three treatments, will they be doing one, and then at some point switching over to the other one? So they will have both, and you can compare how that treatment was working in that same patient? And randomized or nonrandomized. Are they gonna be randomly chosen, or is there gonna be a means of criteria that will dictate what treatment they get? Therefore it’s not gonna be a total randomization. So there are different clinical phases. The first phase is the earlier stages, which more likely than not, you’re not gonna be involved in as much. Usually it’s gonna be more in a lab setting. Phase 2, phase 3, and phase 4, those are more likely as optometrists and ophthalmologists where you can be involved. Because these are gonna be testing on subjects in a much larger base. So phase 2 — the drug or treatment is given to a large group of subjects to see if it’s effective, and to further evaluate its safety. Phase 3, drug or treatment given to a large group of subjects to confirm its effectiveness. Monitoring the side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. So the phase 2 and 3 are, again, fairly easy to conduct. There’s a little more involved in the unknowns. There are gonna be some variables that you might come upon, that you have to address. But the phase 4, we’ve already got it out on the market. It’s already been approved to be used — either by our governmental regulations, or whoever controls that in your country. That’s conducted after a drug or treatment has been marketed to gather information on the drug’s effect in various populations, and any side effects associated with long-term use. Again, one of the easier ones to start off with, because there are more knowns, less likely of extra complications with the treatment or whatever you’re testing. All right. So again, I went over these. The masked versus unmasked, crossover versus non-crossover. One of the questions I did get was: About clinical trials, and is it okay to do a placebo controlled, if there is a known treatment? Well, basically what it all comes down to is: The ethics. So if there is a known treatment to treat something, and it’s 100% effective, then putting this other patient into something that is definitely less effective may not necessarily be in the best interests of the company, or ethically. However, if there’s a possibility that it may work better, may work with less side effects, then yes. You could do it for that. And in terms of placebo, sometimes that’s where you can sometimes avoid that as… You use a crossover. So yes, they may be getting placebo. But at some point, you are also giving them the treatment. So it’s a question that… You know, it really depends on the situation. The disease that we’re trying to treat or monitor, and ethical standards. So… Talking about ethics, we’re gonna go into ethics of conducting trials. So before we can do a trial that needs to be improved by an ethics board or a committee — these are sometimes known as an IRB, an Institutional Review Board, Independent Ethics Committee, IEC, or Research Ethics Board. REB. These are fairly common, no matter where we practice. There’s some entity. What it’s called might be something totally different, but overall, it has to be independent of your study, totally unbiased, looking at this to see: Is this going to be something that is in the best interests of humanity? Is it in the best interests of your subjects? Is it in the best interests of safety to actually conduct this study? In addition to that, oh, sorry. A little too close. There’s the ethics of conducting the study, of the trial. These are just some things that the ethics boards will do. They’re gonna review the protocol, they’re going to review the procedures that they’re going to be doing. They also review the informed consent and any questionnaires. Another question that I had was: Does it have to be all approved? Generally in a clinical trial, anything that could be questioned or asked does need to be reviewed by an IRB or an ethics committee, to make sure we’re not asking it in a way that might bias the answer. That’s a very general, noncommittal — that’s gonna influence the patient to answer one way or another. Okay. So in addition to the ethical boards, we also have certain regulatory bodies that we’re gonna be having to report to in our country. And these are usually gonna be the ones who make the decision, whether the treatment or therapy can be utilized in your country. So for us in the US, it’s the FDA. The Food and Drug Administration. In the UK, it’s the Medicine and Health Care Products Regulatory Agency. And I’ve got the other ones kind of listed — again, each country is gonna have a little bit of a different situation. So this is something you need to be familiar with, before you do clinical trials. How much are they going to be in control of anything? How much — what information are we going to need to provide them, for them to do their job, to say: Yes, you have done a clinical trial. You have done it successfully. Now we can actually use this information to make a decision on whether to put out this treatment or to use this, or whatever the case may be. Once you have all that, once all administrative details are completed and the trial is approved by all parties involved, you can finally start working with the subject. So you have the oversight saying you are good to start. So can I finally actually see the patients now? And do the clinical trials? Well, not quite. Almost there. So the first thing that we have to do is: We need to make sure that we actually have patients to do this. Now, hopefully, before we did the trial, or before we got this all done, we made sure that this was underway. Now, sometimes we can be presented with a clinical trial that says: Hey, we’ve got this new treatment. And it could be totally unrelated to your practice. Or your large patient base. Meaning: I do a lot of clinical trials. If a company comes up to me and says: We want you to do a contact lens clinical study, not a problem for me. I already know, based on my normal patient load, I will have that base. But if for me, as a sole entity, Dr. Chin, yeah, we have a retinal study that we want you to do… Maybe not quite as easy for me alone to do it. Because my patient base is not gonna be as much of the posterior segment as it is the anterior segment. Now, I work in a group practice, I have a retinal specialist available to me, so finding those patients may be still — we may still have that patient population in the practice. But if I were the investigator, and me directly working with these patients, or that interaction — may not be quite as easy as if I, again, I was calling my own contact lens patients that I have seen in the past. And this recruitment that I’ve seen is gonna be one of the major failures or one of the sticking points, of where a clinical trial may be successful, or not successful. So when you are recruiting, you want to see what you have from your patient database. Now, if you are starting something from scratch, on your own, you might — this might already be kind of intuitive. Again, if I were to start a contact lens study, one of the things I might be saying to myself is: Oh, I’ve got this new lens. I think it works very uniquely, to something different. I want to start trying it out. Again, I’m working in that environment. I probably already have those patients that I need to… To get. But if you were trying something — new technology — maybe you don’t quite have to do that. So you might have to look more in your patient database. And maybe look for certain findings in your EMR to say: Oh, this patient might be appropriate for me to contact, to see if they want to do the study. You might have to ask local practices… Local practitioners for a little bit of help. You may not have the sole concentration that you need. Now, sometimes this can be a little bit of a sticky situation, depending on how the dynamics are set up in your community. You may ask a local practice or practitioner if it’s a very competitive situation — they may be reluctant on sending you this patient, because they may feel you might be stealing some of their business. If I’m an optometrist, but the only competition is ophthalmologists, they may be more open to sending you that patient. But that’s just something we have to kind of be open to looking at for finding patients. You might have to do patient referrals. You may need to then ask your patients: All right. We’re doing this study. But if you know anyone else who might be interested, please let them know, introduce them to our practice, and see if they want to do the clinical trial. That’s why I mentioned in the beginning this might be a practice builder, bringing in new patients. You might have to do some media advertising. Some us in larger metropolitan cities, we may have access to a radio ad or TV ad, so we can use that. Those of us that are in a little bit more of a rural area, where the media may not be as big, that might be a little bit harder. But again, another source of where these patients will be coming from, for these clinical trials. All right. So now we’re also gonna be thinking about how we’re going to be conducting the clinical trials. How will you schedule the patients? One of the questions that someone sent to me earlier was: What is block enrollment? Well, block enrollment is just a term that we use, to how are we going to see these patients? Now, with a rolling enrollment, basically what you do is: When I see the patient that’s appropriate, I will get them into the study. So you’re doing your daily routine, seeing your daily patients. Oh, you’re appropriate. Would you like to be in the study? I’m going to bring you in to do the study. Versus with the block enrollment, we might first say: All right. I’m going to find a subset of 20 patients that I need for this clinical trial. And recruit them. But I’m also gonna try to bring them all in on the same day. So I’m seeing all 20 of those patients on the day. And then enrolling whichever I can at that point and getting them through. It’s just a means of how you’re doing it. Each one has an advantage and each one has disadvantages. Without getting too much into it, a block enrollment sometimes allows you to predict your numbers a little bit more, because you know you have this patient coming in. With the rolling, you might have one patient come in now, but you might not have another patient coming for another two to three weeks that satisfies that need. So this would be determined based on your clinical situation, your timing, maybe even sometimes have to do with the protocol. Do you or your trial team members need to learn any new procedures? Whether it be some kind of new testing, needing to learn the new technology, so you can use it on the patients, is there something that you might need some — some specimen you might need to collect or preserve, a technique you don’t normally do in your practice that you might need to learn? You need to make sure that once the clinical trial starts, everything you need to do is second nature or a little bit smoother, as opposed to learning it right then and there. You just need to figure out what type of documentations you’re gonna need. Does your sponsor or the person running the trial want you to do it all electronically? Can you do it on paper? You need to consider what potential problems you might run into, and develop a strategy around them. So this is kind of more just an active thing. I’ve got these patients coming in. Do I expect any adverse responses, do I expect any possibilities, and think of things like that. One of the things we ran into with studies recently is that COVID hit. It’s something we could not have predicted. But you might want to think: Are there things that may not happen, but if it does happen, I have to know how I’m gonna address it, when that comes about. And you need to make sure you delegate the tasks to know who’s gonna be doing what, and their responsibilities. Again, you just want to make sure your office and staff is prepared properly. So you just want to make sure you have all the proper equipment, make sure you know how the patient flow is going, especially if you’re going to be integrating it into your daily routine, or like a rolling study. Now you’re going to be possibly interrupting your general flow. Do you have the means of not making it a major impediment during your day? Can we incorporate that fairly easily? And then again, making sure all your staff knows what they’re doing and making sure they’re trained properly. Another thing that I find is a big thing with clinical trials and why they might fail is just that the protocol is not adhered to, and because of these protocol deviations, the data was ultimately — may have been valid, but was invalidated, because somewhere down the line, something may not have been — even directly involved with it — was not done properly. You just need to make sure that you know the roles of a principal investigator. So the investigator is the one who is actually conducting the trial. He’s gonna be the leader of the entire team. He’s the one that reports directly to the sponsor, the subjects, regulatory and ethical boards, and the research facility. So here are just a few more other things about the roles of a principal investigator. Just for time. Since I’m running out. Now I’m gonna go through it. But again, you are the conductor of the study. You are gonna be the one that has to protect the subject’s best interest. You are the one who is going to be reporting to your IRB, and your FDA standards. You’re also going to be reporting to your sponsors. You’re gonna be responsible for the controlling of the drug and the device that might be under investigation. And you also need to make sure that the informed consent that’s provided is done properly. All right. Another thing is you have to make sure that any records for the study are properly maintained. And you have to be responsible if there are any issues after the study comes about. If there’s a severe adverse reaction or severe adverse event that requires follow-up after a year. Take, for example, a common outcome, which we try to avoid, but sometimes happens, is a subject does become pregnant during the study. At least in the US, it requires the investigator to follow up with the pregnancy and even with the child through the age of 18 to see if there is any adverse response to the child from accidentally participating in that study. So now that we’ve talked about everything, now we’ve got all the administrative stuff done. Now we can finally start the trial. Now, again, I’m not gonna go into a whole lot of details with trials, because a lot of stuff is gonna be protocol-specific. But just generally, if you’re gonna be involved in a clinical trial and you’re an ophthalmologist or optometrist, more likely than not you’re gonna be involved in something that’s gonna be dealing with the eyes. Majority of the testing, majority of the stuff you’re gonna be doing is stuff you do on a daily basis anyway. So it’s not something totally new. It’s not like you’ve been asked as an investigator: We want you to become a clinical site for a COVID-19 vaccine. Which means now you’re bringing in more patients, doing a lot more injections, dealing with a totally different subset. Usually you don’t have to worry about that. But what I want to go over is just how to be successful once you are doing your clinical trials. So as I alluded to earlier, one of the things is basically just: Follow your protocol. That’s one of the things that makes clinical research to a certain degree easy. In a daily routine of optometry, ophthalmology, yes. You’re going to be doing certain things. But you’re not necessarily following a set flow. Your patient may be telling you something, or doing something that was gonna dictate that you have to go with the flow, do something different. But with a clinical trial, it’s a set protocol. Yes, there are gonna be some hiccups in the way, but you know: This patient has to do this step. Then it’s going to be this step. Then it’s going to be this step. These steps may take a certain time. It’s a very predictable — to a certain degree — predictable flow of what you need to do. And as long as you follow the protocol, follow the instructions, there should not be a whole lot of difficulty. Because everything should be dictated along the way. Again, as I mentioned earlier, properly recruit and screen your potential study subjects. One of the sites that does our allergy studies — if I’m doing a study and I need to complete 60 patients with allergic responses, it doesn’t matter if I bring a thousand patients to the screening. If 1000/1000 don’t have allergies, you’re not gonna get that 60 patients. You might bring in 10,000, but you’re not gonna get enough patients to complete it. That’s why you need to find the patients, recruit them initially, to know that yes, I am getting the right subset to make my life easier to complete the study, and they’re gonna provide me with the data that I need for the study. Another thing about it is: Treat this like your normal practice. Although, yes, we’re talking about this separately, when I talk about this in the United States, sometimes I refer to it as a subspecialty of your clinic. Meaning that in the US, some people might have dry eye clinics on top of their regular private practice. They may have: Oh, we do a lot of co-managing of surgeries on top of the regular routine exams. So they treat that maybe a little bit differently. Try to treat this just like you would treat any normal practice. Meaning that you would want to treat your patients the exact same way. You don’t want to treat them as a study subject. You don’t want to make them feel like they’re doing anything necessarily different, in a negative way. You can definitely treat them better, and you can treat them in a positive way, but don’t do it in a negative way. Because stressed patients equal unhappy patients. Part of why I was talking about everything at the beginning is that that will lead to a good flow and a good system. You have a good flow and good system. You’ll be able to treat these patients properly, because these are the lifeblood of your clinical trials, not only currently but in the future. You have this patient. You want to be able to build off of this. You want to be able to possibly bring this patient in for another clinical trial. So now that the 60 you completed this time — maybe it leads to another study that I can complete 80. And next time I’m bringing those 80 back, but now I can complete 100. So you want to make sure you’re treating your patients properly. Because again, stressed patients are unhappy patients. Unhappy patients may not want to return to complete the study or participate in future studies. So this talk, I’m not only just talking about conducting the studies, but also how do we build upon that, to make it a major entity in our practice? Some potential issues. So the patient does not complete all the required study visits. So that sometimes can happen. COVID was one of the things that made it so that a patient didn’t want to come back. Whether it was forced upon them that they couldn’t come back or they didn’t want to put themselves in that environment. Things like that can happen. Adverse events and serious adverse events. I did a study — not totally unusual, but the patient was a little on the older side and suffered a stroke during the study. Probably totally unrelated to the study, but this is something that sometimes occurs that we need to follow up on and take care of. Time restrictions. I’ve had studies where take, for example, a rolling enrollment, doing well at the beginning, then it kind of slowed down, and all of a sudden, next thing you know, we’re in the holidays and it’s a lot harder to bring in those patients. Sometimes you have to take that into consideration. Any unforeseen issues. Again, as I mentioned, COVID-19 is an unforeseen issue that did wreak havoc on our clinical trials. One of the questions I did receive was: Is there anything different in terms of how you conduct clinical trials for the COVID? Broad answer for that, at least in the United States: No. There’s no major changes there. Our clinical trials theoretically are still going as scheduled. Any precautions or requirements that we would normally take in our clinical practice is something that you would do in the… For your clinical trials during COVID. So normally when we would block enroll on a particular day, we might see 60 to 100 patients and block enroll them on that schedule. With COVID, we had to just it, so instead of block enrolling that, we can only do maybe 30 patients during that day. We have to separate it. We have to kind of keep that flow a little more. Nothing specific. But it would just be more… To the same guidelines of how you would control and mitigate it in your practice. So I finally gathered all the results. I did the study. Now what do I do with it? So I’m just gonna briefly touch on what we do with that information. So you have all this information. You’re looking at it. Now what you can do is: If you’re being sponsored by a company, more likely than not, you’re gonna be giving them the data for them to analyze. Because if you’re the only site, they’ll be analyzing it. But if they have a group of sites, they want to take it and put it all together. So again, this is where the statistician is not necessarily involved in it. You won’t have to worry about it. Or you can take the data. You can analyze it yourself. And whether you need statistical analysis to it, that’s where a statistician might be involved. It might be simple enough that you can learn how to do it yourself. So that all just depends. But once you analyze that data, then you can take that and you can present this data. So now this is where you can help your colleagues. I’m taking this data. I might be presenting it as a poster presentation, at a major meeting. Do a paper presentation at a major meeting. I might take it and write it as a journal article, or I could be taking it and presenting it as a marketing campaign for a sponsoring company too. So you can do whatever you want with it. Based on any agreements or stuff like that too. But you’ve collected this data. What you want to do is: It’s for the purpose of helping the optometry and ophthalmology world, so just make sure it gets out there in some way. You want to definitely continue building your database for future trials. So like I said, one trial isn’t all you may want to do. You may want to do more after that. So you may want to build off of that. I did one successful trial. I want to do another one, but on a larger scale, or I’ve done this trial, but it led me to think of something else I want to test. I’ll do that as a trial. And then you can just continue to develop or bid for trials in the future. If it is a corporate sponsor, you just might want to make sure you show that: All right. I have the means of doing other clinical trials. All right. So just to wrap up, before I get to the Q and A session, so in general, clinical trials may not be suitable for every practice or every practice setting. But for those that are, and again, what I mean by that is: You know, as we’re talking about this, some of you are gonna go — oh, a lot of this does fit my need. I want to come in a clinical trial. And some of you might go: Oh, okay. I don’t have X. I don’t have Y. I don’t have Z. Maybe clinical trials may not be best suited for me. That possibly could be the case. But it just may mean that we need to look at it with different means. But basically it’s not… I wouldn’t say it is for everybody. Very small practices, it may not be suitable to make it cost effective. But for those that can do it, it is something that, again, at least as a US-based doctor, it can increase revenue to your practice, in some way or another. Whether it’s directly through the funding coming in, being paid for doing the clinical study, or it could just be the fact that I’ve gotten — I’m building my practice. So the building the practice means more revenue for another doctor or something like that. Again, that practice builder. When it comes down to it, we’re all here because we want to figure out what we can do to better suit our patients. So by bringing this information in, or by bringing in clinical trials, we may be able to serve more of our community. Gives an extra edge over your competition. And it’s a potential way to try and offer new technology, advancements, techniques, and devices before your competition. And again, it’s a way to contribute to your industry and the field. And it can take you out of the rut of normal everyday routines. And lastly, what I want to kind of point out is: In my opinion, the most difficult part of the whole process is the initiation and the setting up of the trial. Cost and time investments at the beginning are gonna be more involved. But one thing I can tell you, based on experience, is that it will pay dividends several times over in the long run, if you continue to stick with it. Basically, whether it’s financial dividends, whether it’s… That satisfaction of contributing, it will pay off in some way. You will get — there will be — there is always gonna be benefits to doing the clinical trials. The more you do, the easier it gets each time. And generally the steps that you will be performing in protocol during the study are the same procedures you do in everyday patient care. So you may not need to learn something new. So again, as much as this may seem that it might be daunting, it may not be as daunting as one looks at it. And bringing clinical trials to your practice not only benefits you. It also benefits your patients, your colleagues, and your industries. Again, that was my main take-home thing about this clinical trial talk. This may not be a direct solution for a patient, but by gaining that information, we are helping not only your colleagues locally, but colleagues around the world, which is the key of, I believe, what Cybersight is. So I want to thank everyone for participating and listening to this. Again, just a brief picture of where I am in the United States, only this would be covered in snow for today. I do want to take — quickly thank Cybersight for giving me the opportunity to allow me to present this information to you. I hope it was beneficial. Here’s my information. I will try to generally answer the questions I have there, but like I said, some were a lot more specific to certain things. If you do want answers to that, by all means, you can definitely email me and I would be more than happy to help you out. Like I said, I do work for a company that’s international, so anyone who might want to try to get into clinical research, we are always looking for sites around the world. I would be more than happy to try to talk to you about that, seeing if it would be something that would be feasible, and then to get you connected with the right people. So I believe I need to go over to my Q and A questions now. Let’s see. It’s there. I totally forgot about the other polling questions. Actually, while I’m pulling up the other stuff, can you pull up another question? Let’s give number two. And then maybe just do three and four, Lawrence, while I get the questions up? All right. It looks like the vast majority have not had any clinical trial experience. Okay. And let’s see what the results are on this one. All right. So at least based on this survey, I think what I wanted to accomplish in terms of inspiring us to just think more about clinical trials, I was successful at that. So let me go to some of my questions that I have here. One question I have here: Do you have problems in recruiting patients in this time of COVID? I would definitely say yes. It hasn’t totally stopped us. But actually, it’s interesting. And I’ll say that COVID is definitely changing things around, and making it harder to find patients, but also from an economical toll — and I can only speak for how we do things in the US — when we do a clinical trial, at least for the clinical trials we do, we are paying the subjects or reimbursing them for their time. So you’ve got those patients that say: No, I don’t want to be anywhere near a clinical facility while COVID is going on. Yet we also have on the flip side saying: Oh, you’ve got a clinical study. Yes, this COVID is impacting me financially. I don’t mind coming in. I would be willing to take the risk for the financial benefit. So more yes than no, but not nearly as much as I would have expected with everything going on. Let’s see. I had a question here. About… When considering a locally produced solution like riboflavin solution for corneal collagen crosslinking, is it necessary to conduct animal model trials? For you as a doctor? I would probably say not necessarily. But I would hope that you would be able to find information that was done on the animal model, and maybe even… Human models, for you to make the decision of whether you would want to use that or not. What is the importance of clinical trials? I think I kind of went over that. The main thing is to try to disseminate and gain information that is gonna help all of us as doctors become better doctors and to treat our patients a little bit better. Let’s see. How to obtain IRB for my studies? Well, that really all depends on where you are. I guess the first thing would be to determine: Is there a particular IRB you need to deal with? Meaning that if you are in a university or institutional setting, a lot of times they already have an IRB set up, in which case you have to go through them. But if you are a private practitioner, there are private IRB companies that you can just look up. For our clinical facility, we have I know two or three IRBs that we can go to. Generally use the same one. Because we’re familiarized with their timing, good turnaround time, easy to work with. But it’s like any company that you work with. Just finding what is appropriate for you. But there should definitely be plenty. I would think even on a very local setting, in a country, there’s still gonna be something that you’re gonna be accessible to. As a student, what first steps should I take to start clinical trials? I would say that if you are early in your career, my best suggestion would be… To find someone in your area and the area that you’re practicing, and get affiliated with them. Perhaps maybe even ask… If they’re doing clinical trials, to see if you can be a subinvestigator. So that you’re not necessarily starting off with the full responsibility, but you can actually learn from them. Basically how I became where I am now is I actually started off as working at the low end of the clinical site, and that was 20-some-odd years ago. I started off at the very beginning, and I actually worked up in the company, worked — eventually became a coordinator, got my optometry degree, so I kind of looked at all the different systems. So probably not the most feasible way, depending on what it is, but just getting yourself into the door, talking to someone who is currently doing clinical trials, so you can work off their coattails, and I would say most people doing clinical trials were doing it for more of the educational aspect of it. And for the gaining information. So they’re gonna be more than happy to help you out, if you wanted to. If you were looking to go that route. How do you decide the sample size of your study? If it’s something you’re working with, someone specifically, a company, they’ll determine it for you. If it’s a smaller study, something you want to do, if you want to get a statistician involved, you can. But it may just be easier for you to say… I just want to get some data out to show that… Yes, there’s a correlation. And if there’s a correlation, this may lead to a larger study, in which case then I can show that there is statistical significance to it. If all the patients do not complete all the study visits, how do we do the final stats? Do we decrease the sample size or calculate with decreasing sample size per visit? That’s a good question. That really all depends. It depends on what the circumstance is. If it’s because they’re not coming back or something to do with the treatment, especially if this is a corporate sponsored study, they probably have to make the call whether we need to go back to the drawing board, and rethink this, based on the data. Or it could be a decision… We’ll do whatever we have and then reanalyze it. It depends on the situation. What is the difference between research and clinical trials? They’re both very similar, but I think in a sense, when we think of clinical trials, we’re thinking more along the lines of… There is actual human entity in most aspects involved. When we talk about benchwork and we do animal work, some people might say it’s clinical trials, some people might not. So there’s kind of that gray area. And when we talk about research, we’re talking about more of the laboratory work. Where we may be working on cells and that type of thing. It’s essentially — clinical trials is research. But it’s just semantics. It doesn’t matter how you’re picking apart what you’re actually doing. Thank you for enjoying it. Where can we find out if the international company is looking for trial sites in Africa? I guess the best way I would start first is… Assume you’re looking in Africa, and I’m assuming that you are allowed to do clinical research in your country. So that would be the first thing. Is seeing if there’s any regulations or limitations of who can come into your country. Then if there is something specific that you are looking to, I would just contact the company themselves. So perhaps is it a treatment that you’re not allowed — that you don’t have available in your country? And you want to make it available? Well, I’m pretty sure if you call a company and say: Hey, we’ve got — I want to bring this to make it available to my patients, but we don’t have it here yet. Can we do a clinical trial to make it available? I’m sure they’re gonna be more than happy to talk to you about it. Because if you can do a clinical trial, in your country, and you can bring that technology that’s not available to the country, for them, yes, again, they’re gonna be investing something in this, but for them, this is a larger population that now they can bring that is gonna essentially help drive up their revenue. So that’s how I would suggest trying to find out — what company, if you want to do something specific, to get it into your country. Can you help with how to convince people for trials? Because I’m a beginner. Okay. Well, I would say that is a little bit of an art form. So if that is something that you’re probably starting off with clinical trials, and may need a little more assistance with, I would be more than happy to try to help you one on one with that. Again, it’s just a little bit… Like I said, it’s a little bit of an art form, in the sense that… It’s almost kind of like talking to patients. To a certain degree, as doctors, we can go in and we can say… All right. I’m doing your exam. This is what I’m finding. Answer any questions. Done and done. But I think we all agree that to be successful in being the doctors we are, we have to work around it. We have to… We’ve developed a skill to learn how to read the patients. Listen to the patients. And adapt our interaction with that patient. So it’s kind of the same thing. You have to learn to adapt to it, and kind of maybe… Without coercing, because that’s the fine point. You don’t want to coerce them. But at least make it look like it might be in their best interests. And if there’s something that you have a treatment for, that they’re having problems finding, they’re more than likely to say: Yeah, I would be willing to do that. I’ve seen every doctor and no one has been willing to help me. But you might have this treatment? I’m willing to do that. It may be just as simple as that. If it’s something that may be more common but maybe you might have to do the financial aspect, saying… Okay. We’ve got this clinical trial. You know, one aspect — sometimes what works for me is: Oh, at the end of the year — it’s the holiday season coming up. If you’re looking for some extra cash, we have this clinical trial. If you want to incorporate, talk about it, you can always ask my staff. So it’s kind of that… Yes, I’m trying to make them interested, but I’m kind of taking the passive-aggressive, by saying… It’s there. You might think about it by looking at another perspective, financial need, but let’s get it going in your brain. If you want to talk about it, talk to someone else. You might have a recruiter or someone who is better at interacting with the patients. In our experience, we sometimes find that the patient sometimes works better associating with the doctor, and not so much a tech. And sometimes where the patient works a lot better with the tech than they do with the doctor. It’s that art of maybe just finding the right person, in your system, to talk to them about it. How do I convince subjects to try out a new treatment. Kind of the same thing. Depending on how severe their aspect is, that might be the factor of whether… Oh yeah. It definitely is worthwhile trying. Or… Yeah, may not be… You may not notice a major improvement. Is it better to start on one’s own or first work under someone? I would probably say it’s probably better if you have the opportunity to work with someone, to work with someone. Because again, I think one of the major things starting off is… I think we are all very intelligent. I think we all probably can handle things very well, but why put ourselves in that situation if we don’t? So if you can at least say — hey, I’m gonna get my feet wet by working with someone — when we think about it, that’s how we all got to this position. Whether we’re optometrists or ophthalmologists, we went through our learning system, and at some point, before we became our own, we had to work with somebody. And I think making those decision makings, when we’re not quite comfortable with — because we had our mentor, our residency director, our fellowship director, whatever the case may be, we had to work with them, it made it a little bit easier and a little bit better that way. Along the same lines, I would encourage you, if you can get your foot in the door that way, go that route. How do we know what is appropriate sample size for a randomized controlled trial? Again, I went through that already. All depends. And if you want — if it needs to be statistical, you use a statistician. Can you go over the phases of a clinical trial? I’m assuming you mean like… Phase one, two, three, four? I had those definitions in it. So if you want, you can review it there. Again, if you have any more specific questions about each phase, or maybe subtleties, I would be definitely happy to answer that in a private email. Just because there’s a lot of different details. And a lot of sometimes — a protocol can dictate whether a study falls on one or the other. What should I do if during my residency I did all the work but at the end the data are published without my name? That I do not have an answer for. I think that is something between you and your residency director. In a certain aspect, I would think that… Yes, you do need to get credit for it. But to a certain degree, sometimes you will be in that situation. What I mean by that is… As a clinical investigator, I would say a lot of the studies I might be doing are… For a corporate sponsor. And theoretically, I’m working for that corporate sponsor. And because I’m working for them, technically the data does belong to them. So sometimes when it comes down to it, I might be… Yes, the investigator and doing all the work. But when it gets published, it’s being published under the name of that company or that head researcher, and then yes, you did all the work, but you might be lower on the totem pole, to not warrant that information there too. So… On a personal note, I might… You know, if it’s already been published… I don’t think there’s anything you can do about it. But if it’s something that’s being worked on, you might talk to your residency director and say: I might not be first author, but at least second or third author, having been put on it. Take, for example… You may or may not be familiar with the CLEK study, which is a group collaboration of the research of keratoconus in contact lenses. So when you look at their research, there is a lot of investigators there. So they are… They do at least mention it there. So… It’s still possible. But again, it’s gonna be more of… A personal thing. One on one thing, how you work that out. But with that being said, if you are interested in clinical research, when you work up that contract, you might want to make sure that… There is an agreement that… Oh yeah. I get to have some kind of recognition, whether it’s… I have an option to present the paper or I get my name on the poster. When you go further in other clinical trials. Another webinar on GP lenses? I can definitely try to work on that. What is the clinical benefit of carrying out trials in the practice vis-a-vis the COVID-19 era? I wouldn’t say there’s any benefits, per se. Again, with COVID, it’s a totally separate entity. Unless for some reason you’re doing a clinical trial of COVID-19 conjunctivitis in patients… Yeah. You’re probably not gonna… Whether it’s COVID or not COVID you’re not gonna gain any extra information. What I will put out there is… Looking at it from a perspective of a private practitioner. One of the things that I have found, that COVID has forced me to do, and I think a lot of doctors will agree with it, is that it’s forced us to look at how we do things in a different way. I think the way I practice is totally different. As much as — as a doctor, I want to go in there and talk to my patients, standard of care and precautions might make it so I can’t spend as much time in the room with them. I do a lot more of the analyzing of data outside the room before I go in there. So that when I go in there, I can talk to them about what it is, and try to be as precise as possible, trying to minimize that 20 minutes in less than 6 feet proximity, that risk factor. So the moral of what I’m trying to say is… We’re taught to think about it differently. With clinical trials, I sometimes present it as: We’re changing our mode of practice. Maybe if I’m thinking about clinical practices now, I’m already in the mindset of changing how I want to do things. It might make it easier like — if we didn’t have COVID and I’m set in my ways, coming in at 9:00, trying to do the — let’s do a clinical trial. Trying to see how to incorporate it might not seem as apparent or easy. But now you’re trying to change things around. I don’t know if that quite answers the question. But how clinical trials might be able to make your thought process different. Do I have to contact a sponsor company myself in order to gather funds for the trial? Not necessarily. That’s within a CRO or SMO can come in handy for you. If that’s something you’re interested in, a particular clinical trial you’re thinking of, outreach to me. I can definitely put you in the right hands, of talking about that. You can definitely go to the companies directly. And say: Hey, I’m practicing in this country. I have this expertise. I would like to do a clinical trial and pitch it right there. It but there might be a lot more hoops for you to get to that person and actually make the decision. As a CRO, typically we deal with a lot of companies. But when we deal with the companies, we know who we want to deal with. It’s the R and D department. Usually they come to us and we pitch it. Sometimes we go back to the country and it’s like… We want to pitch this idea. Would you consider it? And we put you in touch with them or if you’re new to clinical studies, there’s a way that you got yourself in the door, but we’ll be here to help you to conduct the study. That’s just the fell of the American academy of optometry. An extra certification you get in the United States. If you’re in research, optometry, you get that. Will the vaccine be safe to use after phase 3 clinical trials? I don’t have an answer to that. I don’t know enough about the clinical trials of the vaccine itself. Difference between clinical trial and clinical study? Pretty much the same thing. Trial and study are synonymous. Thank you so much. All right. So that looks like that answered all the questions on the Q and A. So again, any other separate questions, something we want to touch one on one, by all means, let me know. I’ll be more than happy to answer it. For any of you who have used me as a mentor for Cybersight for the GP, you know, I’m more than happy to help out any way that I can. Increase the knowledge of anyone out there. Increase the way of treating patients. So again, thank you very much. And I hope wherever you are, you have a good rest of the day or good rest of your evening.
January 27, 2021