So in this series of videos and exercises, we're really going to be looking at putting it all together. We learned a lot of generalized concepts so far about planning for data collection and management, as well as. Potential things that we might consider as we're setting up an electronic data capture system for a study. Here we're going to take a, a look at a, at, at a specific study. We're going to take one from the literature, it's a fairly simple study, but it's, it's an interesting one. And it will give us the sort of real-world use case to, to put all of this together, the thinking and then the doing. Once we review the study we'll brainstorm about data collection. Then we'll do some exercises and And, after those exercises we'll come back and we'll sort of review and, and, sort of circle back and make sure that we're applying. We, we have applied some of those best practice principles when putting together a sample study. So, this is an actual study. It was done at another university some time ago. And I was involved with the, with the team. And it sort of revolved around an interesting principle, or an interesting concept. I was working with an oncologist, and this oncologist was worried about the fact that uh,he had a number of patients. And he had noticed that pain management, particularly in the later stages of cancer, was a difficult thing for him to manage. And I believe one of the quotes he, he gave to me at one point was that you know. I could give half the morphine in the state to some of my patients and it just does not adequately deal with, with the pain manag, pain that they're undergoing. And so, you know, this, this investigator he really wanted to come up with maybe some different ideas in, in treating pain, particularly in these. In these advanced, in, in difficult cases. So he, he did some thinking about it and, and, you know again, the, the problem is that, that the morphine is effective in some patients but, but not all the patients. So he did some thinking about it and I think he was doing some reviewing of the literature. And you kind of notice that THC, the, one of the active ingredients in marijuana, medical marijuana. was also used in pain management. And he, he sort of noticed that, you know, maybe the mechanisms for those are are a bit different. And he had this hypothesis that, well maybe if we combined the two, morphine and marijuana, maybe there would be a synergistic or an additive effect. From the combination of those drugs to be able to, to, to better effectively treat pain. Particularly in those patients where morphine alone was not, not proving effective. So, when we started, he, started thinking about, I, I, got involved in this project from the data management side of it. But he started thinking about, you know, ways that, that you could sort of put a study together and, and test that hypothesis. So, you know, one of the things in, in, in, in, in research is you always need to have controls. And, you know, when we're dealing with either giving a medication or not giving a medication. There's this concept of being able to, if you're not giving them the medication, giving them something that looks and feels like the medication. Something, something called a placebo. So, you know we, we can do testing of drugs by either giving morphine. Or placebo you can give testing of the, the THC by even, either giving a pill. That, that is the active THC you know, ingredient medication or something that looks like it, a placebo. And then we could sort of combine those up, to do the testing for this, synergistic effect. study. Testing pain though is a, is a little trickier. You know how, how do you test for pain? And you know one person may have a difficult, a different pain threshold than others. He may have different stimulus and different sort of, sort of ways of, of sort of Having pain applied to individuals. So there're a lot of confounding factors there in, in the you know, the last thing that we want to do as, as a research study. Is have variability unknown variability in, in the in the way that we put studies together to test hypotheses. And so, you know, the sticking people with pins, or hitting people over the head with hammers. This is sort of considered bad form for a number of different reasons. One of which is the research subjects don't really care for it. So if we're going to do this in a systematic way, and we're going to do it in a way that, the research subject and volunteer community would be comfortable with it. Then, then we needed to, to go in and look at the literature a bit. You know, what, what's been done there before? Let's not re-invent the wheel, let's not try to to come up with a whole new method of applying and standardizing pain. Because if we did that, you know as we said in a previous lecture. That then basically what we have to do is two studies. First we have to go do that process, prove that we can, we can effectively take out the variation in pain, pain administration and, and and measurement. And then we go and do the study with the drugs. So, the investigator went back to the literature and he found you know some good references. Good methodology around applying pain in sort of a laboratory way. In, in this case, one, one of the ways you can do that is through really thermal stimulus. So, the idea being that if you heated a, an iron bar. Up to a certain temperature, and then you apply that to an individuals forearm, you can, you can get enough sort of discomfort there to actually cause real pain. But the discomfort is, is where it stops. You know, you don't have any prominent damage from it, it's, it's, it's a You're not going to have any, any scarring. You're not going to have any real burns on it. It's just enough to have some, some level of discomfort. So if you, if you heat up, iron bars to, to you know, specified predetermined temperature, temperatures. And you apply those iron bars to the fore arm for five seconds, then you've got this very standardized way of of administering pain. so, now we've got, sort of the framework is coming together. We've got the bas-, basic studied procedure is, that what we could give individuals either morphine. Or we could give them marinol, or we could give them a combination of the two, or, or. Maybe a combination of two placebos. And so we've got some, some, some way of administering drugs in a way that, that will allow us to, to make a change that the that, that will be effective. Or may be effective in sort of teasing out this question of. Of whether those drugs either by themselves or in combination are better or worse for patients as, as, as they're feeling. Or volunteers as they're feeling some sort of a pain stimulus. The pain stimulus there in number two, that again is the, is the iron bar that's heated up to predetermined temperatures. again, not hot enough to to cause damage, but, but, but certainly hot enough, so that, so that it doesn't feel like room temperature. And you feel like something is happening there. And those are applied to the fore arm. And then, finally, you get down to the, what about, how do we ask someone whether they're in pain or or not? How do you Sort to get a measurement of, of how much pain an individual is in? It turns out this researcher went back to the literature again. It turns out the researcher kind of came up with the fact that, you know, people measure pain in a couple of different ways. There's this concept of, are you in pain, and how much do you care that, that you're in pain? Would be the way that I would sort of paraphrase things. But and we'll, and we'll get back to that in, in just a few moments. But, but then there's the whole, well, well how do you even quantify that? Are you in pain? How much pain are you in right now? You know, is that a you just sort of let them tell you that in their own words. Oh it's excruciating, or, or this is really horrible. And what about the variability and even the vocabularies of people that are talking about that, you know. How do you, how to you come back and put a number and assign some sort of quantification on that? you know, or do you sort of give them some a scale from one to ten, how difficult, you know, how much pain are you in? Or how much do you care about that pain? So, so you know there's a lot of, lot of, sort of interesting ways to think about that, that characterization of how much pain an individual is in. Again going back to the literature, not reinventing the wheel. this, this research came up with the the fact that visual analog scales have been used effectively for for quantifying pain in the past. And a visual, visual analog scale is really simple. So, you know. Let's take, take the example that we're doing the study that we're talking about. I've taken the drug. You've just put one of those iron bars on me. And, and I'm sort of thinking about how much, how much discomfort I'm in right now. Then we give them a piece of paper. we've got a line on that paper that's exactly ten centimeters long. And we say hey from, from the left end of the paper, no pain at all, to the most excruciating pain I've ever felt in my life. over on the right, just sort of make a pencil mark where you feel like you are in this particular moment. that allows them to sort of have this, this sort of continuous variable. You know, because we're going to take a ruler then and measure where you made your mark. To be able to sort of have this continual variable and you're not remembering that, hey last time I said seven. Is this worse or better than last time? You're not able to sort of compare as easily and effectively. To something that you set in the past, so you're not as biased there. So, so anyway, this visual analog scale was the way that this team decided that they would measure pain. quantify pain for this particular study. Okay so, I think this is, we're about ten minutes into this video. So we'll take a, take a quick break and in the next one we'll come back and we will. We'll look in detail of how we're going to look at this study and particularly the data management behind it.
