Translational Pathway and Ethical Principles in Human Subjects Research

00:01 In this lecture, we're going to talk about human subjects research.

00:04 So now we're going to take the concepts of being responsible clinical researcher, and really think about the human subjects who are involved in that research.

00:12 Have something called the translational pathway.

00:15 So we start from basic sciences all the way through clinical research, and then ultimately to public health, various ways that we might interact with a human participant in conducting research.

00:29 So first, there might be basic research.

00:31 So this is scientific exploration, that is trying to reveal fundamental mechanisms of biology, understand how disease works, behavior works, every stage of the translational research that we think about is going to rely on basic research.

00:48 And it also helps to inform that basic research or otherwise known as bench research.

00:54 There might also be in the translational pathway, something called pre-clinical research.

00:58 So now we're moving from the bench and getting closer to thinking about human beings.

01:04 So in pre-clinical research, we're connecting the basic sciences of disease with now human medicine.

01:11 And during this stage, scientists are developing model interventions to further understand the basis of a disease or disorder and finding out ways to treat it.

01:21 So the ways that they might consider testing or carrying out pre-clinical research might be use of cell or animal models.

01:29 So that might be an example of how it sort of links to human beings.

01:33 There might be actual use of human samples, or animal tissues to try to simulate what's happening in the human body.

01:41 Or there might actually be computer-assisted simulation, where it's, you know, how would this drug work in a computer model? The device or diagnostic test, how would that work, if it were in, you know, in a living system? Then we move into the translational pathway for clinical research.

02:00 And that's where we're going to spend the bulk of our time, but clinical research includes where you're trying to better understand the disease in humans, and now relate that knowledge to findings that you've gotten from the pre-clinical work in the cell or animal models.

02:16 So you're either going to test or refine new technologies and see how that's working in human beings.

02:22 You're going to test interventions to see how safe and effective they are for both people with the disease and people without a disease.

02:30 You might engage in behavioral observational studies that would also be part of clinical research.

02:36 And then also, the actual health services system itself might be research.

02:41 So what are the outcomes of health sciences or health research? And how does it work in the clinical realm? So the goal, when we think about clinical research often is to have clinical trials that we're going to obtain data to support the approval of any kind of new intervention whether it's a drug or a device, you need to generate the knowledge to get ultimate approval from that to then make it available for people with a particular disease.

03:14 After you've done clinical research, the next step in the pathway is clinical implementation.

03:20 So here, you might be doing research, where it's say, adaption of the intervention, you've now demonstrated it's useful in the research environment, but you now want to move it into routine clinical care for the general population.

03:33 So there might be things like cost effectiveness studies to see how does this actually work in the real world.

03:40 So this stage includes implementation research, where you're evaluating the results of the clinical trials, trying to identify any new clinical questions or gaps.

03:48 And, you know, use that to inform, go back to either the drawing board with preclinical research or clinical research, figure out where there are gaps in care, and then trying to implement new processes.

04:01 And then lastly, in the translational pathway is going to be public health research.

04:05 So here, researchers are studying health outcomes of a population.

04:09 So at that level, you're trying to determine what the effects of the disease are, what are the efforts to prevent, diagnose, or treat the disease within the public.

04:19 This is going to help guide scientists working to assess the effects of current interventions at a population level, and hopefully to develop new strategies that are going to work in the community.

04:32 It may include epidemiologic research, so trying to spot patterns, figure out causes and ways to control diseases in certain populations may also be a means of identifying risk factors, and other things that might be more protective factors when you're concerned about particular diseases.

04:52 So that's the whole translational pathway.

04:54 I'm going to focus more on clinical trials.

04:57 So these are research studies that assign one are more interventions to human subjects in order to determine the effect of that intervention on health-related outcomes.

05:08 And those could be both biomedical or behavioral.

05:11 So a person has a particular condition, you're creating an intervention to try to help with that condition.

05:18 So investigational interventions might include things like new therapies or new medicines.

05:24 It might be psychotherapy.

05:26 It might be new surgical techniques.

05:29 It might be new or innovative medical devices.

05:33 It might be different ways of performing a procedure.

05:36 So different techniques, anything that you need to study this innovation to see if it's going to work.

05:43 And often to compare it to what's already in existence, what the standard of care is.

05:51 So all of those, you know, in a clinical trial, or any point in the translational pathway may involve a human participants.

05:59 So we have to have considerations of how to protect a research participant if they are engaged in research.

06:07 So there's some core ethical principles we think about in human subjects research.

06:12 There's something the United States called the Belmont Report, written in 1979.

06:17 This was a means of sort of saying, these are our core principles that all of researchers should consider if they are going to work with human beings as research subjects.

06:29 It's going to be very similar to those that recall our previous lectures on clinical ethics, we talked about principlism and the sort of the core principles of thinking about clinical medicine.

06:43 Here for clinical research, there's going to be a lot of overlap with those same principles.

06:48 So the three principles are respect for persons, beneficence and justice.

06:54 And the way those were typically going to be exemplified.

06:58 So respect for persons is the duty to obtain voluntary informed consent.

07:03 So making sure that the research participant is voluntarily entering into the research, they've been given adequate information about what the research is about, and why they are participating.

07:14 And then they ultimately consent to being a participant.

07:18 Beneficience, the flip side of that is nonmaleficence, if you recall from our clinical medicine lecture.

07:25 So beneficience is doing good.

07:27 So we want to make sure that the benefits outweigh the risks of being a research participant.

07:33 And that if we envision that there are any risks that they are minimized as much as possible in conducting that clinical research.

07:39 And then the last principle in human subject research is justice.

07:43 So making sure there's a fair distribution of the benefits and the burdens of research.

07:48 And, you know, in the Belmont Report, this was written at a time where there was concerns about vulnerable populations being research participants, there's a higher need to think about protecting those that are vulnerable, making sure they're not exploited as research participants.