[BLANK_AUDIO] So we're coming back now, to look at this idea of the synergistic effects of morphine and marinol. In affecting how people perceive and react to pain. This study went on to be published in the European Journal of Pharmacology. And it's a good one for us to take a look at as we think about real world use cases and how we might frame thinking. And implementation of data management principles and practice in the real world. So I should stop here and say that while study design and power calculations are very important for any study, they really are beyond the, the scope of this course. And so we're going to to take those off of the table. And we're going to look at the study design, only really to impact how we might how, how we might put a, put the data management plan together for the study. So never underestimate the need and, and the essential piece of having a good study design and power calculations. But we're going to leave that alone for this course. So if we look at the Methods section of that paper, we see that they studied 13 subjects, seven males, six females. All were healthy, normal volunteers. No current users of opioid drugs and not currently pregnant. They are all aged 18 to 49 years of age. Looking at the drug cocktails we look at four different combinations. There is morphine and placebo, there's morphine and marinol. There is marinol and placebo, and placebo and placebo. So those are the four combinations that could be given before we, we start implementing the pain stimuli as well as the measurement of the reaction to that pain stimuli. If you look at those four combinations and you order them in different ways there are four, 24 permutations that exist for ordering those four combinations. For this study, for this exercise in this class, we're going to assume that there was a look up table that was present at the baseline visit. And that may be drawing randomly out of a hat number between 1 and 24. That would be provided to the pharmacist. the pharmacist would have a code then that would know how, how to interpret those those numbers. And then for each successive visit, they would be able to give in a blinded fashion the drug combinations to, the, the drug cocktail rather, to be administered for a particular participant on that particular visit day. So we'll assume all of that's done back in the background that the study coordinators and team don't really understand what those what, what those cocktails will be. But they are provided in that random fashion, randomized fashion by the pharmacist. There'll be five visits There will be a baseline visit where people come in, they are consented into this study. They are asked for information about themselves, asked about inclusion and exclusion criteria. If they if they consent to be part of this study. Then they will have those pain stimuli and measurements done with no drug present at all for a baseline measurement. After that they'll come in approximately three days apart. And they will come in and they will be given the drug cocktail that was assigned to them for that particular day. Then they will have this pain stimuli protocol, pro applied. And, and the the measurement of the reaction to, to that pain. they'll come back visit to visit about three days apart. And so for an individual, they, they will participate in the study about three to four weeks. although all patients in the study might might be enrolled. And continue on to, to be seen and to to be studied in total over the course of six months or so, depending on recruitment. The thermal stimuli. Read in the paper that the copper stimuli were the, the copper cylinders, rather, were heat, preheated to 37, 39, and 51 degrees sim, celsius, And the stimuli were applied in one of four arbitrary sequences. So if we look at for the, for the sake of this, exercise again, we'll look at the Combo 1 being 37, 49 and then 51 degrees being applied sequentially after one another. Combo 2, 37 degrees and then you would do the pain perception measurements. Then you would apply one that was 51 degrees do the pain perception measurements and then 49 degrees. And do the pain perception measurements. So you'd come in. at the, at the visit start, the coordinator would use some sort of an algorithm. It would get, give them the sequencing of the pain stimuli that were going to be done throughout the protocol that particular visit day. Pain intensity is going to be measured again on visual analog scale. Again, for this exercise, we'll assume that that pain pain intensity is going to be asked on paper. Or that people will be given a piece of paper with a line drawn on it that's ten centimeters long. On one end of the line there's the words no sensation the other is the most intense sensation imaginable. So, this will be how the participants will rank the pain intensity. So they'll be asked hey that, that cylinder that was just applied, how intense as the pain? And they'll, they'll tick off the mark where they feel that, that it's applicable. Then the research coordinator will come behind the scenes and they will measure with a ruler and that will turn that into a numeric measurement. Similarly for pain unpleasantness, they'll be asked in a very similar way on a visual analog scale. Only this time the left hand will be in terms of unpleasantness it'll be not bad at all. The right hand side will be the most intense, bad feeling possible. [BLANK_AUDIO]
