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Mhm. Yeah, that's what you know, just like I'm not sure of that report. Ok. That yes, sir. So hi everyone. Um lots of Clinical Electron for Nigeria. I'll be talking about the overview of clinical trials and um this is just a short by myself and uh I have no conflict of interest to declare concerning this presentation uh as a form of introduction. Uh we're talking about the clinical trials but we need to know the clinical research is the broad arm. Uh that's the branch of medical science that determine safety and effectiveness of medications, medical devices, diagnostic products, nutrition, behavioral changes treatment regimen that anything that is intended for use in medical practice for humans. The that's the branch that takes care of it. And when we talk about clinical trials, this is a subset of medical research, but it's a set of procedures that uh is used mainly when you want to do drug development. When you want to introduce new instrument, new surgical techniques and um various uh behavioral changes and that are conducted. This is to allow for safety for efficacy, data of uh data to be collected for health. So the overall proposal we talk about clinical trials really is for you to see you in have your insurance find new hopes, find new treatment regimen. Mhm. Ok. Mm. Mm. Mhm. So we obtain some things to our group of uh patients and I when we talk about clinical trials, one of the things that comes to mind are the faces of clinical trials and um face of clinical trials become imperative because uh if you remember what have happened in the 19th, 18 twenties, centuries where people have done different studies uh on humans, which are on a and so the phases of clinical trial helps to bring some science to how uh trials are being conducted. And when we talk about the preclinical study phase, we are talking about the homa study. And what happens in this stage is that uh you are not yet transmitting to humans. Uh You are using Homans to test where the new innovation that you have in mind. So if I in the lab, I make a compound that I feel that this can help to cure breast cancer. I'm not going to start using it on breast cancer patients. My first patient or first set of people, I'm going to use it that will be on animals uh to see. Oh, this cancer cells are introduced to animals. When we introduce this drug. Did it make it better? Did it make it worse and all that? And uh it's not surprising to know that majority of preclinical studies phase never makes it beyond that level. When I talk about phase one trials, uh phase one trials, major intention as its way is to test uh safety. I want to know whether this my new intervention is safe. Is this something we can use for people? Is this something we can go ahead? So when it has passed the preclinical phase, the fourth phase deals with limited number of people. Very small number 20 to 80 people, usually LD. People are the people that brought together any informed consent. And uh you are trying to study the safety profile of whatever new intervention you are talking about. When we talk about phase two trial in phase two, that means that uh for it start to proceed from phase one to phase two, the phase one must have being such that the patients already have uh the safety profile of the drug has already been established. So, baseline, oh, this medication is safe has already been established. So in phase two, you are trying to say this thing that safe, is it effective or the efficacy like, so that's what happened in phase two trial. So phase two trial is to know, is it going to really, really do something new? Is it really, really going to help the patient or it's just an exercise in fertility? So when we're talking about phase two trial, that's the mission and you should know that in phase two, the number of participants in phase two is small but not as small as this one. So you can get up to a dozens to 300 patients. Safety profile is being watched and efficacy. If a, a an intervention, uh after phase two was successful was found to be safe, was found to be effective, it moves on to phase three. What happened in phase three is that you have more people in phase three, it's a larger trial. Uh Now you can generalize more what you have your findings because you have a a more bigger group, hurry of people, you can have up to 10,000 participants in this phase. And you are trying to see is this still effective? What kind of side effect are people coming to bring at this stage? And that's what happens in phase three trials. Uh When we talk about phase four, this is usually the post market in phase that is uh we have already uh got an approval and usually uh in Nigeria, we talk about things like dark in us, they talk about FDA. So when approval has already been gotten, this is the post approval face post marketing phase, we want to send it to as many people, but you are still on the lookout of what are the complaints that can come at this stage. And it's very important because something that you didn't find at phase three might be coming up at phase four trial. So when we talk about clinical trials, other thing that comes to mind is that what are the steps? Do? I just wake up and jump and say, I'm going to start the clinical trial. What are the things that will interest me? And if I'm talking, I know majority of the audience this is for medical students, but at least for people that are posted to everything that comes to mind is that for me to say I'm doing a trial, I need to know what exactly do I want? So usually the first thing is that what am I doing? What am I studying? What is my hypothesis? So you, you always have to generate an idea. This is just like every other research. You need to know why do I want to challenge this Pasco? So if I say uh I think this drug will be better for people that have triple-negative breast cancer. I need to write it down and I need to know how visible is the study my my objective. Is it feasible? Is this something that can be done? How do I intend to do it? Those are the things that comes to. So you need to have a research question and an hypothesis and how for you to do a trial, you need to have to design a study protocol, you need to know which phases of the clinical trial to my study fits into. So if I'm the kind of uh researcher that does transitional research and I'm trying to transit to clinical, it's probably going to be a phase one trial. That's good for me. Uh But if I'm a clinician and I want to do a phase three office for office two trial, I need to know who are my w what is my protocol like? So in your protocol things that should be there is uh you have, identify a problem. So usually you don't solve a problem that's not there. So I most identify a problem and that's why developing a clinical research question or hypothesis is very important because you need to have done an extensive search, check your uh your literatures notes so that you don't waste your effort to be sure that it's not that somebody somewhere who is doing the same thing. And there are some clinical trials dot org where trials have been registered, you should have checked and be sure that what you have in mind, you know what somebody is already doing somewhere and you'll be duplicating effort. So it's very important to know that. And when you are writing your protocol, one of the good thing about protocols is that if you write it and you publish your protocol, people can help to the researchers, uh the reviewers, some other people might be able to help you put in some stuff to this protocol to make it better or you, you know, writing the protocol out that will give you an idea to know where there might be his use. So protocol is the standard thing to write out when you are thinking of clinical research, like you do write your introduction, you write your hims your objective. Who do you intend to recruit into the study? What are they, how are they going to impact the other group of people in the society? And what do you intend to study? What is your sample size? How do you intend to reach these people? Who are you going to include, who are you going not to include? On what basis? So that's what the protocol is all about. And it has to be well talked about about the kind of another thing is that now we have a protocol. Now we have a study. Now we have an idea of the kind of patient you want to use. So let's say um I want to do a study on a particular drug trying to find which drug is better for triple negative breast cancer patients. Uh And I've already cause I know my study participant are triple negative breast cancer patient. I want to use Nigerian patient. And the next thing is I won't just grab everybody that comes to my clinic with treating negative breast cancer. I need to have informed consent. What are the people, how they have to consent to this study? So those are the problems that happened in the past that people's consents were not just by using stuff for them. And when we talk about informed consents, we talk about the fact that the patient understands everything. One, the patient, the the consent is written in language that patients understand and they are passed to them in the words that they can, that they can make decisions from. And sometimes the informed consent uh not, sometimes every time informed consents must have uh ability to tell patient that you can withdraw any time. If you don't feel like doing again. If you feel it's not com you, you feel where you feel about the study at any point in time, you can opt out and out of the study should not mean that the patient should not get the best of care. So those are the very important nos when you talk about informed consent and apart from getting informed consent alone, we must know that all is medical institutions like ex that does research. I expected to have institutional review board. There is institutional review board in our hospitals in Nigeria, there's a national uh institutional review board and their work is to make sure that where you are doing is ethically acceptable uh for the patient. And the next phase will be for you to collect your data, analyze your data and uh your report and of paper is found, but I need to know that there are different types of clinical trials uh because usually when people have clinical trials, what comes to their mind is usually the drugrelated clinical trials. That's the treatment trials. But you need to know that even on the treatment trials is the only drug that can be a trial. A form of psychotherapy might be a track uh instrument use might be a trial. So like when people start using laparoscopy, that's a treatment and that was randomized against uh open surgeries. So that's a try um doing uh some endoscopic procedures and all that. It's a trial when they first started. So those are treatments, they are trying to cure something. But there could be other trials like prevention trials. And what happens in prevention trials if uh we have seen over the past people have linked uh cigarette smoking through so many, many classes. But one of the things to do is to randomize people that smoke and that does not smoke and see what happens and observ them. So that's a form of trial. They are trying to see what happens. Screening is and that try like uh most studies shows that mammogram can help uh detect breast cancer and uh reduce the uh risk of mortality going forward. But that's because it has been compared with people that did not screen. So that's a screening trial. So I can notice that oh this certain kind of patients come with, this will make a difference. If we start screening them, you can have a diagnostic trial, you can have a supportive care trial. So you know that clinical trials are a range of trials uh that you go for patient treatment and the patient care general, I talked about head to con consideration, but I'm picking it again for you to know how important it is. We as researchers, as clinical researchers should not be too enthusiastic to forget that the number one rule is do no harm. You don't want to harm the patients, you don't want to do anything. So before you start any form of trial, please, um please submit your protocol for institutional review board approval. And when you get that, make sure you get the informed consent to give full information about the study. It should be very unfair not to let patient anymore. So let me give you an example. If I have a study that has two harms, maybe one har is possible. Placebo means that I'm not giving anything thoracic and the other uh group is going to have a therapeutic treatment. If I don't hear from patients from this past, that it can be in either the placebo, do not place part by part that might be a problem for them and the patients might find it very difficult that oh, I'm not saying placebo uh uh and when they know that they are being given placebo, that might be a problem. And of course, some patient, I said, if I'm not going to get any intervention, why am I to be in this study, which is totally reasonable. So please don't hide anything from your participants. They need to, they need to have the full information so that from the beginning they know what they are getting into so that when they are randomized. So I doubt they, they don't feel bad adverse effects. It is very important for us to be clear about how adverse effects, one and it's very important for us to know how, how we're going to take care of adverse effects. What cascade are we going to put up to make sure that when there's adverse effect, how do we expect people to report it? Because it's very important, especially when you are doing any physis trial, you need to know how you need to set in motion, how you are going to deal with adverse effects when they call, how are you going to report it? What are you going to escalate to? Are you going to stop the patient at that point? Are you going to continue just ask to be? Well, li fact and the patient too should be high compensation still has been a very dicey part because people believe that if I give compensation, am I trying to bribe patients from being in the study? But sometimes you need to know that in my be a little bit difficult for, you know, to compensate patients for some, some studies? But let me give you an example of a study where you need a patient to come in every 22 days uh which is not part of their normal routine of treatment. So you might need to be compensated for their transport pay just for them to be able to come because they are making them incur extra costs, which should not be, I should not be incurring extra cost because I'm doing a study. So that might be something you are compensating for. But it's just that nobody, it's not advisable to, for me to say, oh, I'm starting a study and everybody that comes is going to get the $1000 and I'm sure everybody will want want to be part of the study and that might be cloud their judgment. Compensation should not be the first thing you tell patients when you are trying to uh recruit them into this study, that should be the last but sometimes you compensate for procedures for other things. But you need to know difference between the consent conde uh compensation and difference between inducement of uh research part participant, uh recruitment of participant uh can be from different places. So I'll talk about where do you get patients from? For most medical researchers, we get patients, especially those in regards to the hospital based research patients are got from hospital. They are most likely from a convenience place. Uh You put in a poster in your hospital that oh you are looking for this kind of patients that need this and you can call this number if you are interested. But some bigger uh researches that is in the community might be that you are going to go to the radio houses, newspaper houses or if you are doing study on the rare cases, it might be that you are going to look for physicians that study those rare cases and that and send them messages that if you have patients that have this. And another thing about participants is that if I have the group that I want, and that is representative. Another thing is that, did they meet the inclusion criteria or not? So for every three in the protocol, like I said, that you should have uh factors that make them to be included and factor that will exclude them. So that is very important for them to know I'm going to talk briefly on try designs and um which I know that this is not a compass, but just to give you an idea of the common trial designs that you see, especially when we are talking about the clinical trials. Uh So we have what we call paragra group designs and we have the crossover design and we're going to talk briefly about these groups. And when we talk about this parallel group of design, I'm talking about things going per person that is the commonest. One is uh I'm studying, I'm giving people. Uh I found that there's this drug that can lower risk of a colon cancer. And I'm giving people are at risk for colon cancer, this drug and I know that set of people that are at risk, I'm not giving them. That's just what the commonest kind of uh parallel group is. Just a group of people. I randomize is one set to give a random mice and that said to don't give. But because of so many issues that have been happening with placebo, there are some other things that can come in. I can have more than two groups. I can have a group where I don't give anything. I have a group where I'm giving what they have before. So let's say that the uh we all know that amLODIPine can be used in hypertension and I'm looking for a new drug uh for hypertension, I can say, oh, this group of people that have hypertension, I'm going to give them amLODIPine. And this second group, I'm going to give them new drug. And this third group, I'm going to give them amLODIPine plus the new drug. So they are all parallel. So I, one thing about parallel group design is that number one, they are very easy, they're straightforward. There's nothing clumsy and it can be used for all group of trials. So when we talk about superiority trial, noninferiority trial or Ellence trial, those are just the nuances of the kind of trial you are doing. Super means that I feel that this new drug is better than what we are doing before. But I'm talking, when I talk about noninferiority trial, I'm talking that I don't think there is a difference using this new one, but probably this new drug that I'm going to, uh, talk about is cheaper. Or maybe this new one has a better side effect profile, uh, than the other ones. So, those are the things that happen when you talk about, uh, the, um and you can use to, to achieve this. So private design are easy. They are straightforward. Yeah, it could be costly. You need a long term follow up. So one of the major but uh like a side effect to the fact that uh people, BP rate might be higher because you need to follow people for quite a number of time. So like I said before, you can have intervention against placebo, you can have an intervention against active agents. You can have a multi group designed to many people in one place. I know very amazing uh path out of design that is using in triads is when you have a bacteria design. And what happened in factorial design is that um oh we have oh two to test and uh you can put them into different arms. One of the good thing about bacterial design is that the you can't get use one bid to kill uh one stone to kill double beds because you are using the same trier to get more results. And er, if the result and what you do in the fact, design you to come out, maybe I, I am trying, like the very common example that I have seen in the past was the study that was done using process. And what they did was that the uh nurses of child B in H you gave, you divided them into like four groups. Uh One group was not given anything and that group was given aspirin, another group was given Bet Carotin and another group was given aspirin and Betta Carrot and all that to see what the intervention looks like. So, uh but the thing is that one major fallback of bacterial design is that there must be no interactions in the interactions. That's where the problem comes. What do I mean by interaction if I'm giving two drugs that can interact or that can have addictive side effects that is going to make things work and to make my study to have. So that works. And another kind of trial design that you can have it all cost the crossover design. And what do we do in crossover design? Uh crossover design basically just mean that uh I'm using the same impressions as my uh as my control and that the patient is in my intervention. And this is usually done for when you are studying some rare disease or when you are studying a chronic disease. Uh So let's say I'm studying a chronic back pain and I can't find so many people with chronic back pain. And I'm trying to see whether this intervention is better in chronic back pain. So I might give the patients this drug for a period of time. And, you know, we all believe that pain is subjective pain is what I call it. So sometimes it's difficult to study pain. Right? So, if a patient has chronic pain, I might say, OK, I'm giving you this particular drug for the next six months to tell us how you feel. And we we, we collect data from there. And after six months, we switch to another thing. One of the major drawback of a carryover uh crossover design is the carryover effect. What do I mean by carryover? So if I give somebody drug initially and the drug, uh maybe the half-life is longer and uh I started a new drug, it might be that we are still seeing the effect of the previous drug before the new one as well. Number two, uh there's a way people might not comply. And what do I mean if you start the patient on something that is working for them, now you are switching to another thing that is not working, the chances that they will comply might be very low and all that. So we should know the side effect that comes to that. I'm just going to touch briefly on what randomization means because there is no way we could talk about clinical trials and we're not going to talk about randomization. And like we know, we know that randomized clinical trial is set to be the gold standard of any clinical research. And uh not really, the gold standard is the highest level of evidence that we get. And when we talk about um randomization and uh uh C car uh uh randomized clinical trias, it becomes important for you to randomize people because uh you want to get the results that can be represented, want to get the result that is good enough, you want to get the results that is not biased. And so randomization basically helps to reduce selection bias. So there are different type of randomization and uh I'm going to just talk on the simple ones. So when we talk about simple randomization and these are the commonest one for some of you that would have participated in this study before, in the, in the coding these people to a coin and, and the and just put to whichever one you fall into. But now these are the made better. So now you can have gene uh computer generated data for you. Very simple randomization. What simple randomization of just is that patient come will click. Where should we put this patient? That's just it. So every patient called is to every patient comes you generate from your side. It is a good thing but it has its own drawback. The meaning is that if I'm just randomizing people that let's just breast cancer, breast cancer has been shown that stages or presentation and stages a diagnosis impact treatment uh impact of. So if I want to do a study on breast cancer patients, and I want to divide them into group A and group B and I'm randomizing them using simple randomization without the other nuances. It's possible for me to randomize so many patients with stage three and four in one group, I put so many patients with stage two and three in one group. And by the time I give whatever I want to give the one is stage A that has more of a people with stage one and two, my end up having better. It doesn't mean that the drug is better you random and that's why I I was able to do that. So when you are doing randomization, what is needed for each stage number. So simple randomization is not particularly good for small sample size because it's going to skew your app one way. So you have co that are not accounted for. So it's very important that you know what you are dealing with. So simple randomization are easily achieve, but they might cause imbalance in grouping and that might affect the outcome when we talk about block randomization, what block randomization they want, want to help achieve balance and it wants to be better than once to have simple randomization. So when in block randomization, you have a block of like four block of six and then you randomize people based on that this can be done using complex generation. So, but one thing about block is that still of take into Congress and they cover it and at the same time, block random my station sometimes you can guess. So if I know it's a block of four and um the, the we are randomizing people into a intervention drug, a the normal drug. And I know that they've already somebody has, there is a group of four, right? Somebody has been uh into the intervention drug. So other people have been to the no intervention drug. I can't guess that the next patient between intervention and if as a researcher, we are how humans, if the patient is your friend or something and you know that the intervention drug has not been performing well, you might, you might switch the person over and wait for another person to do, which is very wrong. But it is possible because we are human. So those are the things that can happen with block randomization. So uh it's not without genes own by us. But if it is done properly, it can help you reduce the imbalance in the numbers. We talk about five random. I just try to like a view on what happens with simple random is to give you a better clue. So what do I mean? Like I said, in the beginning, I want when this presentation, what affects my outcome. So what I can do is that I'll stratify how I randomize them. So people that comes with an early breast cancer, uh I stratify them in such that is in one group, late is in one group. So when I'm randomizing people in I randomizing them to either A or B and people in late randomizing them to that A or B. So that helps me to uh cover for my cover. And it might be something else. It might be maybe I, I want to, maybe it, I know that age of patients can affect the outcome. So I might divide people by their age. There are people less than 40 will be randomized to A or B people, less than a people between 40 65 will be randomized to you. B people less than 65. So that's what happens. Uh When we talk about a randomization is a form of that play into the mind of uh we look at the previous person that has been randomized where they randomized to that group. I followed that part. That's why. And I minimization randomization does move the computer generate stuff uh to, to minimize um the fact that move to where she should be and randomization when we talk about blinding blain in the chemical trans