Latest / This Is Why with Dr. Busti / The Steps of Clinical Research & Design Explained

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The Steps of Clinical Research & Design Explained · This Is Why with Dr. Busti

• 0:00
  SPEAKER_00: Hey guys, I'm Dr.
• 0:01
  SPEAKER_00: Bustae, and welcome to this module or playlist series where we're going to be discussing concepts of clinical epidemiology, biostatistics, clinical research evaluation.
• 0:12
  SPEAKER_00: Throughout this series, we're going to focus on understanding how clinical research is designed, how statistical analysis is implemented but also interpreted, and most importantly, how we translate that information into real clinical decisions for the patients that we serve.
• 0:33
  SPEAKER_00: Now, this lecture is part of a larger series available at This IsWhy at Dot Health.
• 0:40
  SPEAKER_00: Now the goal of This Is Why is to help healthcare providers and clinicians understand the reasoning behind the clinical evidence, not just memorize conclusions.
• 0:52
  SPEAKER_00: Each lecture in the series connects to a broader set of topics in evidence-based medicine, clinical research, and the overall interpretation of the medical literature.
• 1:03
  SPEAKER_00: Now, if you find this helpful, I would encourage you to explore the rest of the collection playlist over at thisiswhy.
• 1:12
  SPEAKER_00: Where we continue to build on these concepts in a somewhat step-by-step fashion, even though you can use them individually.
• 1:19
  SPEAKER_00: Alright, now before we begin, let me tell you a little bit about my background.
• 1:24
  SPEAKER_00: Okay, that gives you a little bit of my angle, my bias, my perspective.
• 1:28
  SPEAKER_00: Okay.
• 1:29
  SPEAKER_00: My path in healthcare is somewhat unique.
• 1:31
  SPEAKER_00: I trained as a nurse, a pharmacist, and a physician.
• 1:34
  SPEAKER_00: My current clinical practice is in emergency medicine, and I also serve as an attending physician where I also am involved in teaching of medical students and residents in different programs.
• 1:44
  SPEAKER_00: Earlier in my career, I served in academia, teaching in pharmacy, also in nursing programs.
• 1:50
  SPEAKER_00: I've also worked in public health roles, including serving on major committees with the Texas Department of Human Health and Services Commission.
• 1:57
  SPEAKER_00: That experience and experiences have given me a broader public health perspective that I bring to the discussions about clinical research and those medical decision-making processes.
• 2:09
  SPEAKER_00: I've also been involved in clinical research myself and have published both in medical journals and in books.
• 2:28
  SPEAKER_00: My objective here, guys, is to share that knowledge in a way that helps clinicians make connections between what we learn in training and how those concepts actually apply in patients in the real clinical environment.
• 2:42
  SPEAKER_00: Now, too often, guys, you know this, we learn material in isolation without understanding its endpoint.
• 2:50
  SPEAKER_00: My goal is to help you connect the concepts so that they become meaningful in clinical practice.
• 2:56
  SPEAKER_00: My philosophy of learning is fairly simple, guys.
• 3:00
  SPEAKER_00: True competency comes from understanding concepts, not only memorizing facts.
• 3:08
  SPEAKER_00: Many of us have memorized large amounts of information to get through training to take our exams, but we all know, guys, that memorization alone does not teach you the why or the how.
• 3:24
  SPEAKER_00: And so in this series, we're going to focus on building conceptual understanding so that you can interpret information correctly and apply it appropriately in the proper context of the evidence.
• 3:34
  SPEAKER_00: Okay.
• 3:35
  SPEAKER_00: Now, finally, regarding conflicts of interest.
• 3:38
  SPEAKER_00: Other than owning my own medical education company, I do not have any financial relationships with any pharmaceutical companies, medical device manufacturers.
• 3:46
  SPEAKER_00: I've never served on major speaking bureaus.
• 3:49
  SPEAKER_00: And my only financial exposure to these industries would be through standard retirement accounts that I don't directly control.
• 3:57
  SPEAKER_00: Okay.
• 3:58
  SPEAKER_00: All right.
• 3:59
  SPEAKER_00: Now, by the end of this topic series, you should be able to describe the overall processes involved in design and also the development of clinical research.
• 4:13
  SPEAKER_00: Okay.
• 4:13
  SPEAKER_00: This does not necessarily mean that you must become a clinical researcher.
• 4:18
  SPEAKER_00: I know many of you are going to be a clinician, right?
• 4:20
  SPEAKER_00: You're not going to go in academia.
• 4:22
  SPEAKER_00: However, even if your primary role is a clinician, you still need to understand what researchers should have done in the studies that you should be reading.
• 4:35
  SPEAKER_00: And when you evaluate a journal article, clinical trial, meta-analysis, you should be able to know what elements should be present and whether the methods that were implemented and applied were appropriate.
• 4:49
  SPEAKER_00: Okay?
• 4:50
  SPEAKER_00: Now, second, right, is that you should be able to explain how statistical analysis is determined based on the study design used in the paper.
• 5:00
  SPEAKER_00: Understanding the correct statistical approach and how to interpret those results is essential for applying research to the real patient populations, isn't it?
• 5:12
  SPEAKER_00: Third, you should be able to list the properties and characteristics of diagnostic studies and understand how diagnostic tests are evaluated and also interpreted in clinical practice.
• 5:25
  SPEAKER_00: Okay, finally, you should be able to develop a structured method for reviewing and what I call critical appraisal of the literature.
• 5:36
  SPEAKER_00: Okay, now throughout this series, you we will look at some examples of real clinical trials, some of them that you're gonna be hopefully familiar with, that have changed clinical practice so that you can see how these concepts translate into the actual patient care decisions that many of us make every day and that you take for granted sometimes.
• 5:58
  SPEAKER_00: So my goal is always to answer the questions clinicians often ask.
• 6:04
  SPEAKER_00: You know, so what?
• 6:06
  SPEAKER_00: Why does this matter?
• 6:08
  SPEAKER_00: And how does this affect the patient who's sitting in front of me?
• 6:13
  SPEAKER_00: Right?
• 6:14
  SPEAKER_00: So let's begin by making sure that we're all working from the same kind of definition terminology.
• 6:23
  SPEAKER_00: So terms like clinical epidemiology, biostatistics, clinical literature evaluation, and even evidence-based medicine, many times those words are used interchangeably.
• 6:36
  SPEAKER_00: And there are some of a lot of similarities, but there's some a few distinctions between them that I will break apart over the course of these.
• 6:45
  SPEAKER_00: But from a simple level, right, clinical epidemiology is the study of the determinants and effects of clinical decision by applying uh clinical epidemiologic principles within the clinical environment.
• 7:01
  SPEAKER_00: Okay, in other words, we take methods traditionally used in public health and we apply them to the care of an individual patient that we are seeing.
• 7:12
  SPEAKER_00: Now, biostatistics is a branch of statistics that focuses on the quantitative analysis of biomedical data.
• 7:24
  SPEAKER_00: Okay?
• 7:26
  SPEAKER_00: Now, when we go into, you know, this allows us to interpret the clinical research results, to evaluate the treatment overall effect, to determine whether those observed outcomes that they find will actually be real or are they due to chance itself.
• 7:46
  SPEAKER_00: Now, clinical literature evaluation refers to a process of examining and interpreting research studies so that the results can be used in individual patient decision-making processes.
• 8:01
  SPEAKER_00: This is closely tied to that broader concept, guys, of evidence-based medicine.
• 8:09
  SPEAKER_00: Okay?
• 8:10
  SPEAKER_00: Now, as we move into evidence-based medicine as a high level, I've done other topics on this, and if you need to go back, there is a section on the foundations of EBM, which is critical so that you're oriented correctly.
• 8:25
  SPEAKER_00: But EBM is often misunderstood.
• 8:28
  SPEAKER_00: Many people assume that EBM simply means reading research to guide practice.
• 8:34
  SPEAKER_00: However, the original framework by the original EBM study group describes a very structured process commonly referred to as the five A's.
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  SPEAKER_00: Okay?
• 8:46
  SPEAKER_00: Now, the first step here is to ask the right clinical question.
• 8:52
  SPEAKER_00: Ask first A.
• 8:54
  SPEAKER_00: That usually involves framing the question in a structured format like a PICO, right?
• 8:58
  SPEAKER_00: Patient, intervention, comparison, outcome, right?
• 9:03
  SPEAKER_00: I often expand on this slightly to include TNS, PCOTS, time and setting, because the context when applying the evidence matters.
• 9:19
  SPEAKER_00: Acquire the best available evidence.
• 9:23
  SPEAKER_00: Okay, and this involves doing a searching of the literature, identifying the highest quality of information relevant to your clinical question.
• 9:33
  SPEAKER_00: The third is to appraise the evidence.
• 9:36
  SPEAKER_00: A, the the third A.
• 9:38
  SPEAKER_00: Okay.
• 9:39
  SPEAKER_00: So we have ask, we have acquire, and now we're on appraise.
• 9:43
  SPEAKER_00: Critical appraisal is essential because not all studies are designed or conducted as well as we would like, right?
• 9:50
  SPEAKER_00: And then the fourth step here is to apply.
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  SPEAKER_00: The fourth A is apply.
• 9:56
  SPEAKER_00: The evidence to the clinical situation, taking into account the patient's specific circumstances.
• 10:02
  SPEAKER_00: Now finally, the last and most commonly ignored the fifth A is to assess the outcome that you did in your own practice.
• 10:13
  SPEAKER_00: So after applying the evidence, we evaluate whether those decisions are actually producing the desired results that we saw in the literature itself.
• 10:24
  SPEAKER_00: So evidence-based medicine can also be kind of viewed in this concept of the Venn diagram.
• 10:31
  SPEAKER_00: So you got these five A's, that's the process itself, but you got these three different circles combining together.
• 10:38
  SPEAKER_00: So the first component is the best available evidence or research.
• 10:44
  SPEAKER_00: The second is the clinician's experience and expertise.
• 10:49
  SPEAKER_00: And then third is the patient's specific factors, circumstances, their values.
• 10:56
  SPEAKER_00: Many times we ignore that third one, it gets missed in the mix.
• 11:02
  SPEAKER_00: But here's something important about the Venn diagram, guys.
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  SPEAKER_00: None of those individual circles or elements can function effectively in isolation.
• 11:12
  SPEAKER_00: Clinical experience alone, just reading about or practicing medicine, is not enough.
• 11:19
  SPEAKER_00: Reading the literature and only reading papers and books is not enough, right?
• 11:24
  SPEAKER_00: Talking to patients is not enough.
• 11:26
  SPEAKER_00: None of those can work effectively by themselves.
• 11:31
  SPEAKER_00: So when these three elements intersect, we arrive at the practice of evidence-based medicine and in the context of which it was originally designed, structured, and the framework that it exists under.
• 11:47
  SPEAKER_00: Okay?
• 11:48
  SPEAKER_00: So again, I just wanted to give that high-level perspective.
• 11:52
  SPEAKER_00: Now, let's dive into the actual study.
• 11:55
  SPEAKER_00: How do we go about that process?
• 11:58
  SPEAKER_00: Well, there are important organizations, and we will look at the process of clinical research as typically outlined by the NIH, the National Institute of Health.
• 12:09
  SPEAKER_00: Okay, and they give us some key steps in that.
• 12:13
  SPEAKER_00: The first is that the researcher develops the study concept.
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  SPEAKER_00: This usually begins with a clinical question, or obviously the hypothesis.
• 12:23
  SPEAKER_00: Second is funding needs to be secured if resources are required to conduct the study.
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  SPEAKER_00: Next is, third, the study protocol is prepared.
• 12:35
  SPEAKER_00: The protocol outlines the research question, study design methods, and your planned a priori statistical analysis.
• 12:45
  SPEAKER_00: Okay, next, the researchers must protect the patients and participants by ensuring ethical conduct, that you are following regulatory compliance, often through the oversight of the IRB, Institutional Review Board.
• 13:04
  SPEAKER_00: After that, the study is implemented, monitored appropriately to ensure it proceeds in accordance to the protocol that was approved by the IRB.
• 13:14
  SPEAKER_00: Now, once the study is completed, it's obviously going to be formally closed, the data's done, you start the analysis process, and then finally the results are going to be hopefully communicated to the scientific and clinical community, whether that's in meetings, abstracts, hopefully a real full publication, sometimes online through various programs that are monitoring active clinical research.
• 13:45
  SPEAKER_00: Okay.
• 13:46
  SPEAKER_00: Now, during the early stages of a study, particularly in that concept development, right, and the protocol preparation, there are several key elements that have to be addressed.
• 14:01
  SPEAKER_00: Alright, guys, so that during the early stages of a study, there particularly the concept development and the protocol development, there are several key elements that have to be addressed.
• 14:12
  SPEAKER_00: And let's just kind of go through those.
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  SPEAKER_00: First, the researcher has to clearly define their hypothesis and choose an appropriate study design.
• 14:25
  SPEAKER_00: They must also consider and identify sources of bias and take steps to prevent them before we get started.
• 14:38
  SPEAKER_00: Now, moving on, you need to consider threats to the internal and eventually external validity.
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  SPEAKER_00: You need to determine the appropriate statistical analysis and methods that should be done to analyze the results that you're going to obtain.
• 14:56
  SPEAKER_00: You need to also, if you're doing a diagnostic study, you need to understand the various properties of the diagnostic test that you're using.
• 15:04
  SPEAKER_00: Again, if that's applicable to you.
• 15:07
  SPEAKER_00: Now, importantly, researchers should know in advance the reporting guidelines that they will eventually be using to publish their study.
• 15:20
  SPEAKER_00: I just to take a moment there on that is there are published standards that journals follow, and for the type of study that you do, you should be able to fill in those gaps.
• 15:46
  SPEAKER_00: Before the study.
• 16:26
  SPEAKER_00: And this includes obviously determining the appropriate statistical analysis that you again should have defined, but you're also evaluating the magnitude of the effect size that you saw.
• 16:42
  SPEAKER_00: And you need to determine if those results are actually clinically meaningful, right?
• 16:48
  SPEAKER_00: So it's about determining this the relevance here, okay?
• 16:55
  SPEAKER_00: Determining the relevance.
• 16:56
  SPEAKER_00: So these things become essential components to that, right?
• 17:01
  SPEAKER_00: Now researchers must also consider the possibility of statistical errors, such as type 1 and type 2 errors, that I'll dive into deeper in other topics within this overall collection or series on how to do clinical search.
• 17:28
  SPEAKER_00: You know, if I practice in the acute care environment, I and I'm reading an outpatient ambulatory care study that may not be applicable.
• 17:36
  SPEAKER_00: Now, for clinicians reading the literature, the important question is not simply what are the results, but what do those results actually mean and what do they not mean?
• 17:52
  SPEAKER_00: Okay.
• 17:53
  SPEAKER_00: So after the analysis is done, right, the findings must be clearly communicated with transparency.
• 18:02
  SPEAKER_00: Okay.
• 18:03
  SPEAKER_00: And so that's where researchers should follow established guidelines, things like the consort statement for randomized controlled trials or PRISMA statements for systematic reviews and meta-analysis.
• 18:16
  SPEAKER_00: There are tools out there that guide us, right?
• 18:19
  SPEAKER_00: These guidelines ensure that the studies are reported in a consistent format so that we as readers, you, can easily identify key information, evaluate the methods, and determine whether the results are reliable.
• 18:36
  SPEAKER_00: Okay.
• 18:37
  SPEAKER_00: So as clinicians, we should be asking whether a paper follows appropriate standards and whether the results that are being presented in a way that allows for proper interpretation by us so that we can then extrapolate it.
• 18:57
  SPEAKER_00: Now, before conducting or interpreting clinical research, everyone involved, whether you're the researcher or you're the clinician, should understand several fundamental concepts.
• 19:09
  SPEAKER_00: You should understand the steps involved in the research process that I've defined, how to develop a null and alternative hypothesis, which I'm going to cover basically in the next lecture in this series.
• 19:22
  SPEAKER_00: Recognize the different study designs that are available and could be used, some are feasible, some are not.
• 19:29
  SPEAKER_00: And then understand how those designs influence the internal and external validity, right?
• 19:38
  SPEAKER_00: So we've got to be able to do those three things.
• 19:43
  SPEAKER_00: Now, you should also be able to identify potential confounders, sources of bias.
• 19:49
  SPEAKER_00: We're going to cover that.
• 19:50
  SPEAKER_00: I'm going to walk through examples of those.
• 19:52
  SPEAKER_00: You should be able to determine appropriate statistical analysis and recognize the standards required for reporting statistical findings and research.
• 20:02
  SPEAKER_00: Okay?
• 20:03
  SPEAKER_00: So all of those components matter why we're talking about this, why you're learning this overall.
• 20:10
  SPEAKER_00: Okay?
• 20:11
  SPEAKER_00: Now, how is this module series or this playlist series as part of this overall collection on clinical research, development, interpretation, right?
• 20:22
  SPEAKER_00: Is it organized?
• 20:23
  SPEAKER_00: Okay?
• 20:23
  SPEAKER_00: Well, it's organized in several kind of major, I guess, modules or playlist series.
• 20:30
  SPEAKER_00: So we have study design, development, interpretation.
• 20:34
  SPEAKER_00: All right, we're going to dive deeper into those individual components.
• 20:37
  SPEAKER_00: There's the fundamentals of biostatistics and biostatistical interpretation of those data variables, p-values, 90%, 95% confidence intervals, alpha values.
• 20:48
  SPEAKER_00: Diagnostic testing, things like sensitivity, specificity, positive, predictive value, likelihood ratio, clinical literature evaluation and critical appraisal tools, and the systematic way of how you should be doing that.
• 21:03
  SPEAKER_00: And then other several additional kind of special topics, things like FDA approval processes, pharmacoeconomics considerations, all of those things.
• 21:12
  SPEAKER_00: Now each of these lectures focuses on a specific concept designed to be approximately 15 to 20 minutes in length so that you can kind of learn efficiently and focus on one concept at a time.
• 21:25
  SPEAKER_00: Okay.
• 21:25
  SPEAKER_00: So you they're just organized in formats kind of like this.
• 21:31
  SPEAKER_00: Okay.
• 21:31
  SPEAKER_00: So you'll see special topics around these things.
• 21:35
  SPEAKER_00: And if you need additional clarification or on a particular concept or something, then you can complete the modules in a sequence for a more comprehensive understanding of the overall topic.
• 21:49
  SPEAKER_00: So how to approach these concepts?
• 21:51
  SPEAKER_00: Well, there's traditional teaching, which is kind of like how people taught biostatistics, clinical epidemiology are normally taught.
• 22:00
  SPEAKER_00: Sometimes that's boring.
• 22:02
  SPEAKER_00: It's way over your head, right?
• 22:05
  SPEAKER_00: Sometimes it's difficult to understand, like the person teaching it looks like Einstein sometimes.
• 22:12
  SPEAKER_00: Um, and then there's obviously the thing that we care about, which is the clinical translation of it.
• 22:18
  SPEAKER_00: The so what who cares?
• 22:19
  SPEAKER_00: So that's another viewer angle to help to make the content clinically relevant.
• 22:25
  SPEAKER_00: Okay, so these modules and this series within the collection or playlist can be completed in succession.
• 22:32
  SPEAKER_00: You can follow the series the way we've organized it for you, right?
• 22:37
  SPEAKER_00: Or you can, you know, just randomly pick individual lectures.
• 22:41
  SPEAKER_00: They are designed to be able to stand alone.
• 22:44
  SPEAKER_00: However, there are some assumptions in certain topics in the playlist or series that are assumed that you know about.
• 22:54
  SPEAKER_00: So you might have to bounce back.
• 22:57
  SPEAKER_00: But either way, okay, the goal of this entire series is to help you understand not only how research is to be performed, developed, and performed, but also how to interpret it and apply it, obviously, to real world clinical practice.
• 23:15
  SPEAKER_00: All right, well, thank you guys so much for joining me on this first kind of foundational intro lecture within our series at thisiswhy.health, okay, and on our YouTube channel.
• 23:26
  SPEAKER_00: If you found this to be helpful, continue to explore the other topics in the playlist and series where we are gonna dive deeper and do concepts of study design.
• 23:36
  SPEAKER_00: What are the pros and cons of that?
• 23:38
  SPEAKER_00: Why would you do this study design over that study design?
• 23:41
  SPEAKER_00: Statistical analysis.
• 23:42
  SPEAKER_00: What does a p-value actually mean?
• 23:45
  SPEAKER_00: What does it not mean?
• 23:47
  SPEAKER_00: What does it tell you?
• 23:48
  SPEAKER_00: What does it not tell you?
• 23:49
  SPEAKER_00: Okay.
• 23:50
  SPEAKER_00: All of these things are important.
• 23:52
  SPEAKER_00: The goal is always the same to understand the reasoning behind the evidence so that we can make better patient care decisions in the patients that we're serving every day.
• 24:03
  SPEAKER_00: All right, we'll see you next time.
• 24:04
  SPEAKER_00: Take care.