Why Clinical Trials Feel Out of Reach (and What to Know)

Clinical trials are often seen as a last resort. But what if they’re actually one of the most important options available?

In this episode, Wendy talks with clinical trial expert Kelly McKee about how clinical trials really work, why they’re so misunderstood, and what makes TBI uniquely difficult to study.

They explore the gap between perception and reality, the barriers patients face, and how new models like decentralized trials could make participation more accessible.

This conversation reframes clinical trials not as a risk, but as a critical part of how medicine moves forward.

If this episode changed how you think about clinical trials, share it with someone who needs it.

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Transcript

SPEAKER_01 0:00

Welcome back to Rupture, the world's abessosan. I'm Wendy Lurie. Today we're talking about clinical trials. Clinical trials are built for control, which is as it should be, because that's how we discover and develop new medicines. But for those of us with TBIs, control can be challenging, if not elusive. I'm speaking today with Kelly McKee. Kelly has spent over 25 years inside of clinical trials, working to make them more accessible and more human. We'll be talking about how trials actually work, where they break down, and what it means to redesign them for actual humans, which, for people with TBIs, could be a genuine boon. We are going to talk about one of our favorite topics, clinical trials. Yes. So, Kelly, welcome back to Rupture. This is not your first time.

SPEAKER_00 1:16

It's my second. Yeah, absolutely. So I have been in the clinical trials space for over 25 years. And my whole passion really is about making clinical trials not a four-letter word to people. So clinical trials are the way that new medicines are developed and tested in humans, and they have to be done before every single medicine or vaccine or device makes it to the general. I like to think of them as a future of medicine, as something really cool, but historically they haven't had a really good rap. So I've dedicated my entire career to making clinical trials more accessible, a better experience, and really just sort of changing the word on the street about them.

SPEAKER_01 2:03

Not making it a four-letter word, because it shouldn't be.

SPEAKER_00 2:05

And it isn't. Right.

SPEAKER_01 2:07

We're going to talk about the TBI component of this, but first let's just do sort of a foundational few minutes about clinical trials and what they actually are and what they aren't and what people think they are versus what they really are. And if you could just talk about sort of the basics of trials.

SPEAKER_00 2:23

Yeah, absolutely. So a clinical trial is an experiment. It's to see if a medicine or vaccine or device is safe and effective in a human population. Now, if you ask anybody what's a clinical trial, they think that, oh, it's treating people like guinea pigs or it's really bad things that happened in the past, like the Tuskegee or Henrietta Lax. And yes, we didn't do it very well back in the day, but there is a very strong contingent of individuals, including myself, including you, Wendy, who are really out there to make clinical trials a better experience. There are so many brilliant minds working on science, making things better and better science-wise. And so I like to think of myself as doing that on more of the operations end. So, how do we make clinical trials better for patients? How do we make them an option for people? Most patients don't know what a clinical trial really is. Most doctors don't really understand what a clinical trial is. And so if we think of them more as the future of medicine instead of a last-stitch effort, I think that we can really come to understand the value of clinical research and the value of participating in clinical research.

SPEAKER_01 3:46

That's great. I actually have two follow-up questions there. Most docs don't know what a clinical trial is.

SPEAKER_00 3:53

Yes. So a clinical trial could be part of a one-day lecture in medical school. And I mean, come on, medicine is hard. Like these students, there's a lot that needs to get into their brains, right? And so they really just don't even really understand. They just say, oh, that's what the academic medical centers do. Or, you know, I live in Boston. That's that's what happens at Mass Gen. And yes, it is, but when we look at it as a very narrow lens, we're really not allowing the majority of people to consider them as an option. Every time I go to a new doctor and they ask what I do, and I explain what I do, they say, Oh, I haven't thought about clinical trials since medical school. Or that's what UMass does, or you know, MassGen does. And I say, Well, would you be interested in participating or as a physician? And they say, Well, I don't even know where to begin. So if we think patients have an issue, like doctors have an issue too, and they're not presenting clinical trials as that option to their patients.

SPEAKER_01 4:57

That's fascinating. And it does explain why the communication breaks down in terms of people participating. Last question on the basics. Can you explain the phases of a trial? Because you'll see headlines about such and such a thing did great in phase three, but do people know what phase three actually means?

SPEAKER_00 5:13

Absolutely. So in order to get to testing in humans in clinical trials, first a new medicine is discovered. It's discovered in the lab. And then it goes through testing in a test tube. So they're looking at the molecule, how it reacts to different things, et cetera. Once it passes that, it goes into animal models. And once it to make sure that it's you know safe for then going into humans. Once it goes into humans, there are four different phases. Phase one is generally healthy individuals, and that's to see what happens to the medicine inside the body, and then what happens to the body when the medicine is inside the body. This is usually done in healthy volunteers, except in situations where it's not safe to put the medicine in a healthy volunteer, like in oncology or in gene editing. And then you're looking at individuals who actually have the condition. These are very small, they happen quickly, and it's really just to see: hey, what happens when we put this new treatment, uh potential treatment, into a human. The next phase, once it passes that, is phase two, where we're actually looking at the treatment inside of a group of individuals who have the disease or condition that we want to study it in. And we're looking there for safety. Is it a safe, is it a safe treatment? And if it passes that, it then goes into phase three, which is a larger cohort of individuals. And there we're looking to see is it safe and does it work? And that's called is it effective. So once we go from then phase one all the way through phase three, then we submit that data that we've collected on the individuals to regulatory authorities like the FDA. The FDA looks at all of that data. If they determine that it's safe and effective, it then becomes a marketed product. And you see all those commercials for those uh Yes, we do. Yes, we do. And but it doesn't mean that the testing stops. Phase four is called post-marketing. And so that's when we're looking at how does this drug behave in individuals long term or in different indications, etc. So, yeah, there's four different phases. A single drug entity can go through and often goes through multiple phase two and phase threes because each different indication has to be tested for that safety and efficacy.

SPEAKER_01 7:49

That makes sense. Um when you said the the last one, when the the post phase four. Yeah, is that also is that the same as the real-world evidence? Yes. That's what we're collecting at that point, is how it behaves in the wild?

SPEAKER_00 8:02

Exactly.

SPEAKER_01 8:03

Okay, okay. All right, let's turn the lens a little bit on TBI, since this podcast is about TBI. Um what do you think makes TBI? I have my own theories, but you're much closer to this. What makes TBI sort of a harder area to do trials in than other conditions?

SPEAKER_00 8:22

I think there's lots of reasons, and I want to hear yours too. So I think the first is that TBI is really it's a name for a whole lot of stuff, right? So not everybody look looks the same, not everyone's journey is the same. And so, and there's like multiple components in TBI, right? There's your acute phase and then there's your long-term phase. And because it involves the brain, which we really don't understand a whole lot about, it's really difficult to understand like what do we want to target? What are the biomarkers? You know, what are the is it about symptom control? Is it about recovery? Like, where do we even want to start? And so that's really hard. And then because everything is so subjective, it's also really hard to measure. So let's say you're working in type 2 diabetes. That's pretty straightforward. Did the medicine lower your blood sugar?

SPEAKER_01 9:21

There are markers. There's great quantify it.

SPEAKER_00 9:24

Yeah. In TBI, like what are you even looking at? Are you looking at better quality of life? Are you looking at ability to do more things? Are you looking at a specific biomarker? Do we even know if that biomarker exists? And so it's really, really difficult. And the other thing that a clinical trial is like, it's like science, right? We want things to be easy and measurable so that we can see an outcome and see if it's safe and effective. In TBI, just you know, talking to various patients, no one has the same story. Nobody has the same journey. So how do you even measure that?

SPEAKER_01 10:02

So I agree with all of that. That some of the symptoms are measurable. Not the pain and not what's seen on a scan, because scans tend to be clear. But some of the things that actually can be measured are the deficits. So the deterioration of, say, vision or loss of speech and language. I mean, there are some things that can be quantified, but there are a lot of things that can't be. So the subjectivity is definitely a piece. And what you said at the beginning, the symptoms varying so much. When you moderated our panel and you had three of us with TBIs, we had three completely different sets of symptoms. So what are you running a trial to fit to try to solve?

SPEAKER_00 10:39

Yeah. Exactly.

SPEAKER_01 10:40

Plus the difficulty of understanding the brain and the limitations of how much we understand. So it's uniquely vexing.

SPEAKER_00 10:48

And there's more, right? So in order to participate in a study, you have to go through something called informed consent. And that means that the study is explained to you by a doctor and you are fully consenting to be a part of that study. You understand the risks and the potential benefits, you understand what's expected of you. With TBI, sometimes you don't have that ability. And so caregivers are involved. And you know, it could be a long-term situation. And so many people could argue that can a TBI patient even provide true informed consent?

SPEAKER_01 11:27

Which probably depends on the severity of the TBI and all the other factors. No, it's true. And actually, that's that kind of gets into the next section, which is like who would qualify for a for a trial for a TBI? Because I mean, to your point, it does it need to be someone who's capable of giving informed consent, or can a proxy like a caregiver do it? Like how how would you even sort people for a TBI trial?

SPEAKER_00 11:55

So caregiver can give consent if they have the right power of attorney. And a caregiver is really important because you're not just participating, they're participating too. I did a quick look at clinicaltrials.gov, which is not it's not a great site. It's not very patient-friendly, but it's what we have. And if you look at type 2 diabetes again, there's a lot of trials being run, thousands. In TBI, currently recruiting, it's in like the low 200s last time I looked. So there's not that many. So that's an issue, number one. Number two is that they're run primarily at academic medical centers. Now, think about your journey as a patient with TBI. Can you travel a great distance? The average distance is about two hours to your nearest academic medical center multiple times a month for years? Probably not. And so the way that we've constructed clinical trials traditionally has been at these large academic medical centers. We expect patients and caregivers, if appropriate, to travel long distances, to take even more time off of work. And one of the things we talked about, you know, on the panel is that work is not the same post-TBI. And so life is not the same post-TBI. And can you even fit that into your day-to-day life? Do your symptoms allow you to fit that into your day-to-day life? Because part of being in a clinical trial is following the schedule of assessments so that everybody is as uniform as can be. So that makes it very difficult. And so one of the things that I'm really excited about is looking at alternative methods of clinical trials, of coming to patients' homes or doing more video visits, or, you know, scheduling really around the needs of the patient instead of making the patient fit into the needs of the study.

SPEAKER_01 13:52

So it sounds like what you're describing is what we always call patient burden, right? And it's this is a hard thing for people to do. So I know a lot of your work has always been centered around reducing the burden and making it easier for patients to participate. So can you talk more about decentralized trials, the trial coming to you, anything that you're working on or you're aware of that's trying to reduce the patient burden so that they can participate?

SPEAKER_00 14:17

Yeah, absolutely. So decentralized clinical trials, it's a funny name because it's really not decentralized, but it's the name that we have, is when one or more activities is are done outside of a traditional academic medical center or what we call a brick and mortar site. It can look anything from doing completing a diary, so saying how you feel on a on your own phone or a tablet. It could be a video visit or a phone call with the physician instead of having to go into the academic medical center for some or all of your visits. It could be going to a local pharmacy to collect your labs instead of going into that academic medical center. Or it could be using what we call a modern clinical trial site where we're actually bringing the trials to the patients' homes. So it's a combination of your doctor being on a video call like you and I are on right now, providing medical oversight to a trained and qualified research nurse who actually comes to your home. So the doctor uses the nurse's eyes and ears and provides that medical oversight. The nurse is doing everything in your home. So collecting blood, taking measurements, processing everything, shipping it off so that the trial really revolves around you, the patient, instead of you fitting into the trial.

SPEAKER_01 15:48

Which makes sense, but but it's taking this a long time to get there. How quickly are we moving in that direction of uh well, the decentralized trials and making the patient the center as opposed to making the trial the center?

SPEAKER_00 16:01

Not fast enough, but we are starting to collect really important data. So we're starting to see trends that there's a lower placebo effect. So a placebo is something that looks like the medication, but isn't. And it's important that we look at uh placebo-controlled trials to see if the medicine's actually working, right? Because part of having brains is that we can convince ourselves that something's working when it really isn't real. And so we are starting to see that when a patient is comfortable in their own home, they don't have that like white glove syndrome. So they're not performing for the doctor at the hospital. I'm sure you've seen this in your own journey. Like when you go to the own blood pressure. Exactly. Right. And so we're seeing that um not only in adults, but really with kids too, which is just amazing because they're just so much more comfortable in their own homes. Um, so we're seeing that that placebo effect could be lower, which is great because then you can see if the medicine's really working. Um, we're also seeing that by broadening the catchment area of patients to that other 92%. So about 8% of people in the US live within about a two-hour drive of a large academic medical center. The other 92 don't. So when we open up the rest of the country, then we're able to enroll a more diverse and representative uh group of people. You want the people enrolled in the trials to look like the people who are going to take the medicine once it's approved. So if you enroll people who are just old retirees with lots of money and time, that's not what America looks like. And so it's really important that we study the medicine in the people who are eventually going to take it. And when we bring trials to people, we're seeing that we're enrolling a much more representative group of people.

SPEAKER_01 17:59

So, first of all, I think a lot of people who do not work in the clinical trial space would be surprised to find out that the people who are recruited for trials or who are participating in trials don't necessarily look like the people that the medication or the device is intended for. I think most people don't know that and just assume that, say, drugs for women are tested on women and you know, and different ra different racial and ethnic groups are represented, so we're sure of it, but it's not really the case, is it?

SPEAKER_00 18:30

It's open mostly to everybody. There are some, you're not gonna do a prostate cancer study in women. Okay.

SPEAKER_01 18:36

So there are limitations, good. Let's be clear about that. Absence of prostate makes that impossible.

SPEAKER_00 18:43

But generally, and aside from phase one, where sometimes we don't want to enroll women of childbearing age for obvious reasons, generally, yes, it's open to everybody. But the people who can actually participate because the way a protocol is written, because of the the travel required, because of you know all the burdens of participating doesn't necessarily look like the people who will actually take the medicine. And so when we're looking at is it safe and effective, different people respond to different things. And as we talked about in TBI, everyone's experiences are different with TBI. So like your experiences are going to be different too in how a potential medicine, you know, reacts in your body.

SPEAKER_01 19:28

Yeah, that makes sense. The only other thing I wanted to say when you're talking about the placebo part was I read a study a few years back that said that because we know the placebo effect is real, right? And we know that the power of the mind to convince oneself that something is working or not working is real. Apparently, the placebo effect even works when people know it's a placebo.

SPEAKER_00 19:48

And that's wild.

SPEAKER_01 19:49

Still works, which is wild, right? But it's true. And they've repeated the study, and it's it's really fascinating.

SPEAKER_00 19:56

And it varies by geographic area. So in South America, a lot of companies don't want to do tests there, clinical trials there, because the placebo effect is so great.

SPEAKER_01 20:08

Really?

SPEAKER_00 20:09

And so I was working in you know Alzheimer's disease research a long time ago, and you know, running studies in different parts of the countries is is very a different experience. In Latin and South America, it's all really centered around the family. And we saw, you know, that sometimes the placebo effect was greater. And so when I talked about like the placebo effect being less when you're bringing trials to people's homes, then you can really see the difference in the active treatment versus the placebo, and you want that difference to be great.

SPEAKER_01 20:43

That's super interesting. That is super interesting. Okay. Next part. Uh the decision to participate in a clinical trial. When does it make sense for a patient? I mean, you can answer from a general point of view or TBI point of view, or preferably both, but when does it make sense to consider participating in a trial?

SPEAKER_00 21:00

So traditionally, trials were seen as a last ditch effort or hope. I like to think that trials should be considered as a care option as early as possible. Think about it. The future of medicine is in clinical trials right now. So why wouldn't you want the best? And a lot of times they're not even placebo controlled, they're active comparator controlled. So if there is a medicine that's if there's a medicine that's already been approved on the market, then you're not going to look at what you're testing versus placebo. You're going to look at what you're testing versus what's already on the market. And even if there's nothing that's really like what you're testing in certain populations, like oncology patients, there's no placebo. We're looking at the active drug that we're testing versus standard of care. And so if you're a patient, And there's a standard of care out there, or there's a potential new treatment. Well, why wouldn't you want the chance to go in the potential new treatment that could be better? So I like to think that clinical trials should be an option for everyone. It's not the right option for everybody. That's what you have to decide with yourself, with your doctor, with your family and loved ones, but wouldn't it be great to have it as an option?

unknown 22:24

Yeah.

SPEAKER_01 22:25

So, I mean, you've spent your career talking to patients and trying to figure this out from their point of view. What do patients perceive the risks of a clinical trial to be versus what the actual risks are? Like what what what scares people when you're starting to talk to them about this?

SPEAKER_00 22:41

Well, we use a lot of big words. And the informed consent looks like when you had to sign a mortgage application with paper.

SPEAKER_01 22:51

Or your Apple, Apple Ts and C's that nobody reads, right?

SPEAKER_00 22:55

Exactly. But you have to read it. And so it's very daunting. And so a lot of people just say, whoa, whoa, whoa, I can't even do this, right? Because you're dealing with a TBI or a new diagnosis or your whole life, right? It's just, it's a lot. And so a lot of people get thrown off by the informed consent. But a standard of care treatment has its own risks and potential benefits as well, right? But you're not signing that form when your doctor's prescribing a medicine that's already been approved. So there's that. There's the burden. So you have to take off work unless your, you know, work allows or you, you know, have a very flexible job or you're not working. You have to do a lot of extra things. Sometimes that's good, right? You're getting extra visits with the doctor. People generally say that, oh, when I go into my doctor for a checkup or whatever, I get to see them for 10 or 15 minutes max. I mean, even when you're going in for a normal visit, you're spending 30 minutes, maybe an hour with your care team in a clinical trial. And so a lot of people say, I really liked the experience because I'm receiving more of that one-on-one care. But generally, I would say that it's just an access and awareness issue. I've been a participant in clinical trials. I can tell you that I'm really glad that I did it. But it was also very eye-opening because we still, we still are placing a big burden on people. The technology doesn't always work. The instructions always aren't very clear. And so I think it's really important that as professionals in the clinical research industry, it's important that we have those experiences as patients as well.

SPEAKER_01 24:33

That's actually the perfect segue because I was going to ask you next what it actually feels like inside a trial. But you can do it from two perspectives as a participant, but also as someone who does this professionally. So what is it like inside a trial?

SPEAKER_00 24:47

Okay, so I was a patient in a COVID vaccine trial during the pandemic. And I was super excited. I was super excited to hear that they were developing a vaccine because as an extrovert, I do not do well in isolation. And I said, hey, it is my time to do this. I have been working in this industry for decades, asking people to participate. Now it's my turn. It was really hard for me, me, knowing everyone in the industry, knowing, you know, how to navigate the system, finding who was running the trials. I knew that it would be, you know, MassGen or Boston Medical Center or one of the big academic medical centers. But then really finding which doctor was running the trial, getting in, and I actually had to phone a friend. I had to phone a friend who's a physician at Boston Medical Center and say, get me, help me get into this trial. He did, and he actually enrolled as well. So that was good. I had to travel to into this into a pretty rough area of the city, but it was during COVID, so it took me about 15 minutes on a general day today. It would take over an hour. And then the technology didn't work. At times I wanted to throw my phone against the wall. And this is me knowing the value of, you know, doing this. Um when I received my instructions, they were on paper and some words were crossed out and things were written over. I know it we were running at like warp speed, literally, to try to get these vaccines out. But like those little things, because this is such a well-controlled scientific experiment, like going that extra mile at the end really makes a difference. Now, there were really some good things about it too. At the end of the treatment period, they unblinded everybody. And so those people who got the placebo didn't get the vaccine, were vaccinated. So I was the 15th person enrolled into the trial in the United States. And so I was one of the first vaccinated. In fact, when it was time to show my employer, we were both working for the same company at that time, that you were vaccinated, they rejected it because it was outside of the window. And I had to get a note from the study doctor that yes, in fact, I really was vaccinated. I was just one of the, you know, the early ones in the clinical trial.

SPEAKER_01 27:00

It was a scary time.

SPEAKER_00 27:02

It was a very scary time. And also, I actually received a thank you that a lot of people don't. So I received a medal that said, you know, one of the first people to receive the uh the vaccine. So that felt good too. And also the world's back open. So I feel like I played a little bit of a part in that.

unknown 27:18

You did.

SPEAKER_01 27:19

You did. Yeah. You use some language in there that I think would be great to explain. So blind, we could throw in double blind.

unknown 27:27

Yeah.

SPEAKER_01 27:27

And the and also talk about the arms of a trial.

SPEAKER_00 27:30

Sure. So I'll start with arms. When you are looking to see does the medicine work, you want to see in the same sort of people. So that's called inclusion-exclusion criteria. So you're bringing together people who have a similar profile, but different enough because it matches the people who are eventually going to take the drug or vaccine, et cetera. You want to see if they all respond similarly or different. And that's part of the safety and efficacy that we talked about earlier. So there are different arms of a trial, and you're randomized into those arms. So it's like flipping a coin. In a two-arm study, you'll look at the active drug versus a placebo, or it could be that you're looking at active drug at a particular dose versus active drug at a different dose versus maybe standard of care versus maybe placebo, and then that's four different arms. And I'm just making this up. So then there's blind versus double blind. In a blind study, your doctor knows what treatment you're on, but you don't know. Because if you're on placebo, of course you're going to say it's not working. And double blind is where neither you nor your doctor know what you're in. Double blind is where you want to be because we all have biases. And if a doctor knows what you are on and you don't, they still might not be asking you probing questions to see how you're doing, if you have any adverse events, because they know you're on placebo. So double blind is the gold standard.

SPEAKER_01 29:15

Why aren't all trials double blind? Since that is the best possible way to do them.

SPEAKER_00 29:21

Yeah, so most trials going into phase three are all double blind. Once you go into post into phase four post-marketing studies, sometimes they're just blind because the drug has already been proven safe and effective, and you're just doing further studies.

SPEAKER_01 29:39

Okay, this is really helpful. Thank you. Okay, so that then people will read a headline that says such and such a trial failed. Failed, failed. It's big headlines, right? I mean, everyone's interested in clinical trials. This gets what they get a lot of ink. What does it mean to have failed?

SPEAKER_00 29:54

So once a drug goes into human testing in phase one, there is a 90% chance that it will never reach the masses. And that's by design, because we want to see if the drug is safe and effective. And not everyone is. In fact, only 10% are. So if a trial fails, it means that the test that was run in that trial didn't prove didn't prove itself. So if the test is, is drug A at dose B safe and effective in patients with TVI? And the answer is no, then the trial failed. It doesn't mean that the drug doesn't work. It means that maybe we didn't have the right dosage. It means maybe that we weren't testing in the right population. Or it could mean that in people it doesn't work out so well. So we're doing our job when trials fail, because we don't want everything that looks good in the lab or in an animal to just go into the masses. We want to make sure that we're doing our due diligence to test that drug.

SPEAKER_01 31:08

So sometimes the drug the drug fails, but sometimes what you're saying is also the design of the trial is the problem.

SPEAKER_00 31:15

Yep.

SPEAKER_01 31:16

Okay. That that's helpful also because people will just see the drug failed. Done.

SPEAKER_00 31:19

Right. Yeah. But it's like how you're testing, right? So you could have a basketball, and if you don't put enough air into it, it's not going to work. There's nothing wrong with the basketball. There's problems with you pumping it up enough. So is it a user error or is there a hole in the basketball? Let's do some more tests and find out. And that's a very simplistic way of looking at it.

SPEAKER_01 31:45

It's a great one, though. That's a really great way of explaining it. That's okay, cool. So you mentioned clinicaltrials.gov. Everybody should know that if they want to know what clinical trials are are available, that's where they should go. Is there any other way to find out? I mean, I know it's a Cluji website and all of that stuff. We've all spent our time there. How else?

SPEAKER_00 32:07

Yeah. Well, you can do research online. Artificial intelligence is really great for this, actually. So asking questions like explain clinical trials to me or what clinical trials are available to me. You might see advertisements. Uh, it's called direct-to-patient advertising. If you take the subway, there's the tea here in Boston. If you look up, you'll see all of these different advertisements. If you're on social media, you might see some advertisements. You might be approached by your doctor. If you are, that's fantastic. Or you might learn about them through patient advocacy or about or from a friend or family member. There's not enough education and awareness out there. So that's one thing that we really need to change. We need to make clinical trials available and an option for more people. But we are finding more and more people are looking for opportunities on their own. One of the things we talked about on the panel is that TBI patients aren't satisfied with the options that are out there. And so one of the commonalities was that all three of you were looking for your own options. And clinical trials could be one of those options.

SPEAKER_01 33:17

And for all three of us, clinical trials were have never come up in conversation.

SPEAKER_00 33:21

Exactly.

SPEAKER_01 33:22

As we talk to our providers for a host of different reasons, but just didn't come up. But it's exactly very, very true. But I just had to um are the clinical trials you see mentioned in social media, like how do people know those are legit? Only because we know there are a lot of things that go on on social media, say with influencers, and you want to make sure that if you're a community, if you're trying to reach someone or you're interested in participating in a trial, that it's coming from somewhere you can trust.

SPEAKER_00 33:49

Absolutely. So when you click on an advertisement, it will take you to something called a pre-screener. At the and that's just a website that asks you a couple yes and no questions to see if you might be a good candidate. Read the privacy statement. The privacy statement will tell you which pharmaceutical company is running the trial. If you don't know the company that's listed, Google it, see if it's real or not. The other thing you can do is actually take that information to your doctor. Not all doctors are open to clinical research, but some are very friendly towards it. And they might say, hey, let me take a look at this and I'll let you know what I think. If your doctor says, I don't do clinical trials, I don't know, then unfortunately you need to do more research on your own.

SPEAKER_01 34:40

So okay, that's interesting. And you mentioned, you know, pharma check to see which pharma company. Is it only pharma companies who sponsor clinical trials?

SPEAKER_00 34:50

If a medicine is to be approved for use, then yes, most of the time, it could also be an academic medical center or a doctor running a trial on their own. You want to make sure that it's legit, right? Like it's a real doctor, it's a real hospital, a real pharmaceutical company. In the nutraceutical phase, so those are plant-based medicines, supplements, they don't have to go through the same testing that a commercial drug does. And so some of them may do some clinical trials, but it's different rules and regulations. They're much more loose. So I focused my career on the pharmaceutical clinical trial.

SPEAKER_01 35:34

Yeah. Well, and it's really interesting and relevant that you brought up the nutraceutical piece because one of the things that is frequently recommended to people with TBIs are supplements. Yes. And I know, because I worked in the space, that supplements do not go through the same kind of rigorous regulatory process as pharma does. Um, but I don't think a lot of people know that. I think a lot of people assume that it be it goes through the same FDA process.

SPEAKER_00 36:03

They don't know that, even though there's a disclaimer on your medicine bottle, but like not medicine, sorry, supplement bottle, but like who's who's reading that?

SPEAKER_01 36:12

Who's reading that?

SPEAKER_00 36:13

Take it to your doctor and talk with your doctor about it because supplements also have effects on the body. And so it's really important for your doctor to understand what you're taking and how it might affect the treatments that you're already on or the treatments that you want to be on.

SPEAKER_01 36:32

That makes a lot of sense. So we talked about patient burden as sort of an access, it's a barrier, right? So what are the other barriers to people participating? I mean, there's a geography piece you talked about, people could be two hours away, right? They might need to get find childcare or have someone cover their their a shift for them. I mean, it's what are what what are what am I missing in terms of other factors that could be barriers to people participating?

SPEAKER_00 36:59

The logistical barriers, absolutely. Getting there, taking the time off, finding childcare, et cetera, the financial barriers.

SPEAKER_01 37:07

Many Yeah, what are the financial barriers?

SPEAKER_00 37:10

So participating in a study does not cost you anything for the procedures or the treatment, potential treatments that you would get. But sometimes they don't pay for things like time off from work or time for your travel or paying for parking or paying for the meals that you eat when you're outside of the house. So a lot of uh studies actually do provide what they call as a patient visit stipend, which should cover that. You want to make sure that that works for you. More and more are you know covering that, which is wonderful. There's the time, the time burden. And then there's the fact that you actually have to do stuff, right? Like you have to pay attention to how you're feeling and report that back. If you have any, we call them adverse events. So if anything happens to you, you have to report that into the doctor. So there's time with that. You just have to really like pay attention. And so it can be very intense, especially if you're for a TBI patient who's already overwhelmed. And Wendy, we didn't say something in the beginning, which I think is really important. Neither you nor I are doctors, and so this is not personal advice.

SPEAKER_01 38:21

No, absolutely not.

SPEAKER_00 38:22

It's just our personal opinion.

SPEAKER_01 38:24

That's all it is.

SPEAKER_00 38:25

Yeah.

SPEAKER_01 38:26

We don't diagnose, we don't treat. We're just having a conversation about clinical trials. That's all. Exactly. Yes, and thank you. Thank you for keeping us honest. So I want to go back to the informed consent piece. So, how does that work, how could that work for TBI trials?

unknown 38:43

Yeah.

SPEAKER_00 38:44

So, first, your doctor has to determine that you are able to understand an informed consent and the process and be able to make that informed choice. And it's a process. I mean, there's a document you need to sign, but informed consent is a process. You can drop out of a trial at any time. You or your doctor can determine that, and that will not affect your future care. There are ethical review boards that review all trials before they go into human testing. And the, you know, the FDA also has oversight of that as well. But your doctor has to determine that you are of sound mind and body, that you are able to make that choice. And if you're not, that you have the right proxy. So you have the right caregiver who can help you or make that decision for you. It's a little different in kids because there's something called assent and consent. When a child is under 18, they can't make that decision without their parent also agreeing. Once they're in that older child group, they can they have to say, yes, I want to participate, and then the patient, and then the patient's caregiver also has to say it. So there's like it's double for kids and some other vulnerable patient populations. But you have to be able to make that choice. And then you have to be able to make that informed choice. So it's really important that you ask all of your questions, that you take the time to say, yes, I want to participate in this, and then you know that if it ever, if you don't like it and you don't want to do it, you don't have to do it.

SPEAKER_01 40:23

So be because cognitive issues often go along with a TBI, one of the things I've learned just from my own TBI is that the symptoms aren't static. They they keep changing, some get better, some get worse, some leave, some join. And and that happens with cog with cognitive issues during, you know, throughout a someone's TBI journey, has to do with emotional issues, and all these things change. And someone's willingness and ability to participate may change throughout the because trials are not short, right? How long can it might a could a trial take? Months, years. So, I mean, I've watched my symptoms change multiple times over the three and a half years. How how does a trial account for the fact that someone's abil, like I said, their ability to participate may sort of wax and wane during the trial?

SPEAKER_00 41:12

So that's where the process comes in, the informed consent process comes in. So both you and your doctor and your caregivers and loved ones have to say, hey, I don't think this is working for me anymore, or yes, I still feel comfortable doing this. And so informed consent is a process, and you really just have to have that open and honest uh feedback channel with your with your study doctor.

SPEAKER_01 41:38

Is there a way to make the informed consent process less onerous?

SPEAKER_00 41:43

Yes, there is. The first is to write the informed consent at a reading grade level that's appropriate for the patient population. Uh generally, we like to see them at a fifth grade reading level or below. Sadly, most informed consent documents are written at an eighth to tenth grade reading level, which a lot of people can't understand, especially in a vulnerable population, like if you have a TBI. We can also make them look less like mortgage documents and be more interactive. So using something called e-consent. So showing videos on the computer about what your visits will look like, walking through the procedures. Not everybody learns by reading. Lots of people learn by doing, or by somebody telling them, or by watching. And so it's important to have that like multimodal uh opportunity for individuals to learn how they want to learn. Another way is to actually ask patients what they read at the end. So a little quiz, if you will. A lot of people don't know.

SPEAKER_01 42:54

This is another thing CBI patients love is a quiz on something they just had to read.

SPEAKER_00 42:57

Right. Um not great for like the touchy-feely stuff, but maybe important.

SPEAKER_01 43:06

So just a few more questions about the kind of at-home decentralized trials. Remote monitoring. What are what what can you monitor and how well does it work?

SPEAKER_00 43:18

Yeah. So really the purpose of a clinical trial is to collect data to provide to regulatory agencies like the FDA to show that your the treatment is safe and effective. That data can look like your blood pressure, your weight, your height, laboratory tests, any symptoms you're experiencing, etc. Traditionally, when I started my career back in the nineteen hundreds, as my children like to remind me.

SPEAKER_01 43:52

That would be eighteen hundreds, so I've got you being no way.

SPEAKER_00 43:56

Everything was on paper. And so we had to Individuals called clinical research associates would fly to different hospitals and monitor the data. And that means they're looking at what was written down to provide back to the pharmaceutical company versus what was in the patient's chart and make sure that they match. That's called monitoring. We have evolved since the 1900s to the point where most medical records are on the computer now, and most clinical trial data is being entered into the computer as well. Because they're in electronic systems, we don't have to fly clinical research associates all the time all over the country to monitor the data. We can do it remotely. And that's really sped up the way that we can collect data and then ultimately submit it to the FDA.

SPEAKER_01 44:56

Makes a big difference.

SPEAKER_00 44:57

Yes.

SPEAKER_01 44:58

All right, so here's the closing question. If you could tell patients one thing about clinical trials that would change how they approach them, what would it be?

SPEAKER_00 45:07

Clinical trials are the future of medicine, and you have the opportunity to help make new medicines possible.

SPEAKER_01 45:15

So I mean Exactly.

SPEAKER_00 45:18

Um I went to a talk once where a patient stood up and he said, I'm not a guinea pig, I'm a test pilot. And think about that. Test pilots are really cool. I mean, they just flew up to the moon yesterday in Artemis, right? They're looking at new frontiers. Nobody would say they're guinea pigs. And so we need to start looking at clinical trial and clinical trial participants that way too.

SPEAKER_01 45:40

That's great. That's perfect. And I love the the one two of like the universal, you're doing something good for science and medicine, but also like you personally are making this. I mean, there's a private and a public. There's a perfect message. Yeah. Thank you so much. I mean, I thought I knew a lot about this topic, and I've learned a lot as I always do from you. And thank you so much for sharing your insight and your expertise and for coming back to Rupture.

SPEAKER_00 46:04

It's always fun to talk to you, Andy.

SPEAKER_01 46:10

Thanks for joining us for this week's episode of Rupture, the world's a Best Guess stand. Today's episode featured Kelly McKee, and we talked about clinical trials and TBI. If this episode resonated with you, or if you know someone who could benefit from hearing it, please consider sharing it with them so they may find our community. And to support our work, you can like, comment, subscribe, share, or join us at bestguessestan.com. Bring us your rupture. Bring us your systems failure. We'd love to hear your story.