What Clinical Trials Really Look Like: A Patient Advocate's Guide (Part 1)

Clinical trials can feel overwhelming, confusing, and even frightening, especially for patients navigating a new diagnosis or searching for better treatment options.

In Part 1 of this two-part Rupture conversation, Wendy welcomes patient experience expert Kelly McKee and patient advocate Mindy Cameron to explain how clinical trials actually work from the inside out. They break down the terminology, the people involved, and the realities of participating in medical research.

Together, they discuss:

• What clinical trials are designed to prove
• The role of placebos and standard treatments
• Endpoints, biomarkers, and informed consent
• Inclusion and exclusion criteria
• The many professionals behind every study
• The real-life burden placed on patients and caregivers
• Distrust, fear, and misconceptions surrounding research participation
• Why patient voices and experiences deserve greater recognition

This episode offers an honest, patient-centered look at a system that shapes nearly every medicine and treatment we rely on today.

Subscribe to Rupture for Part 2 of this important conversation on patient advocacy and the future of clinical research.

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Transcript

SPEAKER_01 0:00

Welcome back to Rupture, the world of Best Guess Estan. I'm Wendy Lurie. In an earlier episode, we took a look at clinical trials from a 30,000 foot view. What are they about? What are they trying to prove? Who's behind them? But today we're going to do something different. We're going to go inside a clinical trial. To understand what it's like day to day, what are the expectations? What's the experience? Who are all of these people and what are their roles? And to help answer those questions, I'm joined by two clinical trials experts with different but complementary perspectives. And they are going to take us inside a process most of us only get to see from the outside. Here's that conversation. Those of you who've been following the series at home will recognize Kelly McKee. Kelly has spent her entire career on the patient side of clinical trials, making it easier for people to join trials, to stay in them, and also she does a lot of work to think through how it can be overall a more positive experience. And I'm super stoked to welcome our newest guest, Mindy Cameron. Mindy is a highly respected and very well-credentialed patient experience and advocacy professional with deep and relevant expertise. So welcome both. Welcome back, Kelly, and welcome Mindy. Thank you.

SPEAKER_00 1:42

Happy to be here.

SPEAKER_01 1:43

I'm very happy to have you. Clinical trials are something that's super interesting for a lot of people, but there's also a lot of misunderstanding and mystery. So we really want to get into that with the first part. So the first part is what's actually happening in a clinical trial? Who are the people? What are the expectations? What is required of patients? There's just so much that people don't understand. So, Kelly, I'm going to start with you, right? We're going to just to set the table. So clinical trials can feel intimidating from the outside. And people want to know like, who runs them? Who makes decisions? What does participation look like? How do I sign up? What are the expectations on both sides? So let's start with. Can you take us through basically, you know, what a clinical trial really is beyond what people read in headlines? And what are trials actually trying to learn or prove?

SPEAKER_00 2:32

Sure. And this could probably take five hours, but I'm going to connect it into maybe two minutes. Clinical trials are the way that new medicines, vaccines, or medical devices are approved for use in humans. And so when a new drug treatment, et cetera, is identified, it goes through a series of tests to make sure that it's safe and effective for the general population to take. Clinical trials are the human part of that, right? So they undergo laboratory testing and sometimes, many times, animal testing to make sure that they're safe before they go into humans. And then clinical trials are when they're actually going into humans. So it could, it sounds scary, it sounds scientific. It is scientific, but it's not scary because we have some of the most brilliant people in the world working, either for pharmaceutical companies on the sponsor side, for doctors on the site side, actually providing the medical oversight to patients, and then to the patients who actually participate in the studies as well as their families. Every single person who participates in a study contributes to that medicine being made available. And so whenever you're taking a medicine, you have to thank the people who really, you know, participated in the studies. There's lots of paperwork to fill out so that you understand the potential risks and benefits. You understand what the uh what's going to happen, how many visits, if you'll have to travel to a doctor's office or hospital, or maybe you can even do it at home. And so there's lots and lots of uh specifics that occur within a clinical trial. But basically, clinical trial is the way that new medicines are developed. And, you know, I'm gonna invite Mindy to talk a little bit about it too, because she and her family have participated in trials.

SPEAKER_02 4:22

Thanks, Kelly. Yeah, we've participated in seven or eight either observational studies, natural history studies, and then interventional studies. And interventional studies, I think, is when you're actually trying a new therapeutic intervention, whether that's a device, a biologic, uh, a small molecule, which is a pill. So it can vary, but I think the from the patient side, most people that are entering clinical trials, I would venture to say, are new. They've got a new diagnosis that they're trying to navigate and learn about. If the diagnosis is not new, they've probably been on trying different medications and maybe frustrated or desperate to try to find something that works. And they're also, if they're new to this, they're navigating this whole new world of clinical research. And I think it's important for everyone to remember that most people have never really heard much about clinical trials. You typically enter a clinical trial because you've just learned something is up with your health or your child's health. I have a lot of experience working with children in pediatric clinical trials as well. So I think from from the multi-stakeholders that are involved in clinical trials always need to remember this patient mindset when they're entering into this trial. They're they're confused. They are not as knowledgeable as they feel like they should be to enter into something as important as a clinical trial. They put a lot of trust in their doctors and in these companies that are running the research. So I think that's where we all need to start from is understanding this may be commonplace for us that are professionals in the space, but for a patient entering into this, there's a lot of unknowns and a lot of learning to do. And it's a whole new world when you when you are looking at a clinical trial for the very first time.

SPEAKER_01 6:06

Well, and another thing that makes trials sound scarier are is the language. So I just want to throw out some of the words, and if you guys could define them, because this isn't how humans speak, right? This is how this is how clinical trial professionals speak, but not how people speak. So placebo.

SPEAKER_00 6:24

So placebo is something that looks, tastes, smells like the the drug or the treatment that's being tested, but it actually contains nothing. The reason that some trials are placebo controlled is we want to see if the drug actually works and if it's not just in your brain. The human brain, as we all know, is very complex. And sometimes when we're taking something, we can trick ourselves into believing that it's working. So the reason that we have placebos involved is that you think you're taking something, but you really want to know if the drug, uh, the active drug that's so is active versus placebo is really working. Now, the number of placebo-controlled studies is really limited when we don't have a standard of care that's available on the market. If there's a standard of care available, then we're usually looking at standard of care versus the new treatment option. Another common misconception is that in oncology you're getting placebo. No, you're not. You're getting the standard treatment. So it would be very unethical to give cancer patients, you know, placebos.

SPEAKER_01 7:33

Okay, what's an endpoint?

SPEAKER_00 7:35

You want to take this endpoint?

SPEAKER_02 7:38

Sure, sure. I I work a lot in rare disease, and you know, I just want to just mention from the placebo standpoint, oftentimes in rare disease, you are in a trial and it's the very first uh you know, it's the very first therapeutic agent that's even being developed. So um, and you're also dealing in pediatric disease, you're sometimes dealing with, you know, something that's happening to your child or happening to you, and and the the idea of a placebo can not can be unattractive, especially if a trial's running for a very long time, which happens a lot in rare disease. Endpoints are tricky. I think oncology endpoints are are, I don't want to say simple, but when when you compare them to like a neuromuscular disease, for instance, you know, you can see tumor shrinkage, you can see blood biomarkers, you can see things that when you look at rare disease or something that's slower progressing and that has a lot of variability among patients, endpoints can be extremely difficult because a lot of times in in the space I work in primarily, you're you're looking at functional tests, time tests. There's a lot of variance in that. Um, there can be variance for within patients on the particular day. So we look a lot at biomarkers and surrogate endpoints too, evidence that that this interventional agent's having some kind of effect in the body to try to get earlier approvals to shorten these timelines. Because we we can run into very long trials when we're looking at just functional endpoints. So there's a lot of work in in rare disease, and I suspect in the broader chronic diseases as well, to tie something that you're seeing in the body, a biomarker. That's what that means. It's happening inside the body. It's not necessarily apparent on the outside that's got a reasonable likelihood of affecting disease progression. And but usually regulators want you to tie that surrogate endpoint with some kind of clinical outcome. Clinical outcome means an endpoint that you can see. And this is one of the challenges of drug development is endpoints for sure.

unknown 9:33

All right.

SPEAKER_01 9:34

I mean, there are many, many more words we need definitions for, but we'll I'll stop with two more and you guys pick which ones you want to take. Informed consent and inclusion criteria. Informed consent, Kelly, I'm looking at you.

SPEAKER_00 9:45

I'll take informed consent. Informed consent is actually a process where the individual participating in the study is fully informed and agrees to participate in the study. You can say no to any clinical trial, it does not affect your medical care. You can you can drop out of a study at any time. It does not affect your medical care. Your doctor may choose to remove you from a study. Again, it does not affect your medical care. So the informed consent process begins by having a conversation with your physician, the study physician, about whether or not participating in a trial might be the right choice for you. You then progress into signing the informed consent document. And this is a document that can be four pages long or it can be 40 pages long, depending on the complexity of the study. And it really just goes over who can participate, what happens when you participate, who to call if you have any questions, etc. But the informed consent process does not stop when you sign that paper. It should be an ongoing conversation between you and the study team. So you cannot participate in a clinical trial, though, unless you sign the informed consent document and it's signed by you and the physician.

SPEAKER_02 11:00

I guess that means that leaves me with inclusion criteria. Yeah. So you've got inclusion criteria and exclusion criteria. These can be very frustrating to patients. So when you're developing a therapeutic, you really need to look at a group of patients that are similar. Because when you've got a progressive disease, you can have all kinds of variability between young patients versus older patients, different stages of disease progression. So inclusion criteria is what the parameters you need to fit within to take actual part in the interventional study. Exclusion criteria can be extremely frustrating. That can be if you're on certain medications, you cannot participate. If you're too far progressed in your disease, sometimes you cannot participate. If you're if you're not progressed enough in your disease, sometimes you're excluded. There's a lot of criteria around reproductive health. You know, some things that are very personal in nature can include can exclude you from a trial, which I think I think this is one of the more difficult aspects of a trial for new newcomers to clinical research to grasp why certain patients are excluded. If they've all got the same condition or the same disease, why can't they all participate? It can be extremely frustrating when you have advanced disease and you cannot participate in a trial. And sometimes, you know, we're in the age of amazing innovation, particularly in rare disease, and you've got extremely expensive therapies hitting the market. And sometimes payers will look back at that inclusion criteria too, which adds a whole nother layer of frustration because just because you were excluded from the research portion of a new therapeutic doesn't necessarily mean you should be excluded from receiving that therapy as pay as on a commercially available therapy. So there's a lot to think about. I work a lot in exclusion and exclusion criteria. Sometimes it's it's very stringent, and that's it's difficult for people to understand why it has to be so stringent, but it's because in order to see drug effect, you need a similar group of patients. And that can be incredibly difficult, especially when you're working in rare disease because there's not that many patients to begin with, and you're trying to find a subset that are very similar.

SPEAKER_01 13:11

Thank you. That's really helpful. Okay. My next question is sort of titled, Who Are All These People? So I worked in the space, so I know who all these people are, and I'm just gonna rattle them off and you guys explain who's who. Okay, so we've got the principal investigators, the study coordinators, CROs, CRAs, sponsors, patient-facing staff, safety monitors, and 15 others. Who does the patient interact with and who are all these other people?

SPEAKER_02 13:37

I'll start this one because Kelly's gonna know about a lot more about the details. But from the patient perspective, which I feel like I've this is what I'm here to talk about. And I and I I think I've said I look I've worked a lot in pediatric indications. So your clinic coordinator probably is the most important person to you when you're participating in a trial. That's the person that you're gonna see when you come into the study site, or that you're gonna see when they potentially like through a telehealth visit if it's a if it's a decentralized setup. Your your nurses and the staff that are actually taking care of you, doing the blood draws, doing the functional testing, really being there with you during the day. And then I think there's a difference to to be discerned between a site lead investigator and then the the PI of the entire study. So I've been fortunate to to actually participate in a trial where the PI of the entire study was running it. And that's that's that was a very nice thing, but that's unusual. Usually you've got, you know, you've got your, Kelly correct me if I'm wrong here, but you've got your site PI, your site investigator, and then they've got staff underneath them who are actually dealing more, you know, one-on-one with the patients. But then you've got a PI of overall of the entire study, and then they're working with the sponsor.

SPEAKER_00 14:46

Yeah, so if we start from the patient at the core, which the patient should always be at the core, right? The next level is the site level. So at the site level, you have the principal investigator who is responsible for the safety of the patient, as well as ensuring that the protocol, so protocols like the roadmap of the study, is being followed. Then there's a lot of people who help the principal investigator. There are other doctors, they're called sub-investigators. There are nurses, there are clinical research coordinators. Sometimes in larger doctors' offices or hospitals, there are people who are entering the data into computer systems. Sometimes there are people who are solely responsible for finding new patients and recruiting them into the study. And there can be, you know, some other administrative functions. The next layer could be either a CRO or a sponsor. A CRO is a clinical research organization and they help sponsors by actually running the study. Sometimes a sponsor is doing all of that operational work, sometimes a clinical research organization is doing that work. So for the purposes of this conversation, we're just going to say sponsor. Sponsor is a pharmaceutical company who is paying for the trial to occur, is collecting the data. So that's uh all of the endpoints that Mindy talked about earlier, all of the uh, you know, your vitals, how you're doing, clinical outcomes, et cetera, per the protocol. Again, that's that roadmap. And then submitting that in that's what we call a clinical study report. Think about like a report you would write in in high school, right? So ran this experiment, this is the report. That report, along with all the supporting documentation, goes to uh agencies like the FDA, who then look at that data and determine if the drug is safe and effective to either go to the next stage uh in clinical research, the next phase, or to be approved for the general public. So I don't know if I got all of your acronyms. We got most of them.

SPEAKER_02 16:56

Yeah, those of them. I should add that sometimes those those see those clinical study reports and supporting documentation can be thousands of pages. The amount of data that regulators are looking at, especially in in modern trials, and you think about data collected through wearables, you know, you've got sensors that are also recording movement and and blood pressure and heart rate and and all these different monitors, all those data points, all the all the clinical endpoints, all the patient reported outcomes, all the all the the work that you did to structure the study and develop the protocol, it's they're massive. I think people often wonder why it takes so long for regulators to um r review a drug application. The amount of data in these dossiers for for drug for uh interventional therapeutics is massive. Yeah.

SPEAKER_00 17:48

When I started my career, it was back in what my children call the 1900s. Everything was on paper. And sometimes the amount of paper that was needed would fill up a tractor trailer. So a tractor trailer full of boxes of paper would be delivered to the FDA, and then they would have to sort through all of that. Now it's all on computers, so it doesn't look that big, but it's huge. And it's a lot more needy even than it used to be.

SPEAKER_02 18:18

Sometimes the FDA will let you do a rolling submission, so they're they're they're starting to review information as you as you gather it, as you submit it. And I think that's a that's been an important improvement to try to cut down timelines. But timelines are becoming more difficult, I think. With more data is always good, but processing that data can be quite difficult. And then we could have a whole nother webinar, our our podcast on how we're starting to think about AI and and deciphering all that, but that's another topic for Okay, we'll set that up for another day.

SPEAKER_01 18:52

Mindy, I'm gonna turn to you in a second, but Kelly, first of all, I wanted to thank you for defining protocol because that was one of the words on the vocabulary list. So thank you for taking care of that. Okay, now I want to talk about, and Mindy, this is really for you, how patients enter the system and what participation actually looks like.

SPEAKER_02 19:08

Well, that I think I this has one of been one of the biggest learning curves for me in my in my career as a patient, as a like a professional patient advocate, because I worked in rare. I have a lot of experience in rare, which hopefully I'll be back to talk about my own personal experiences and why I got involved in all this. I think patients with a rare disease are seeking information. They're attending patient conferences, they are asking their doctor, they know their child or themselves has just been diagnosed with a rare disease, and there's not, it's not like an oncology trial or a blood or diabetes trial where you've got, you know, our Alzheimer's trial, you've got thousands of patients. We're seeking out treatment. So we will sometimes patients will go to the doctors and say, I heard about this trial, I've heard about this company. What do you know about it? Other times, it's very much up to what your doctor knows about clinical research. If they're finding out, there are most pharmaceutical companies have entire departments called like field medical reps that are going out talking to doctors about drugs that are in development or drugs that have been recently approved. So there's a huge educational piece, educating patients, educating advocacy leaders, educating doctors about trials that are happening. Unfortunately, some of our more well-known clinical trial sites, like a website where you could go and try to find a clinical trial.gov. They're incredibly intimidating to patients. You put your thing in and then you get excited about a trial, then you realize, oh, it's not, it's not recruiting, it's it's no longer enrolling. What does that mean? Like, is it is it done? Is it over? There's a lot of confusing information on some of these websites. And some and again, back to my point, these are these are people new to clinical research. Those trial sites can be pretty intimidating. So there's a lot of a lot of activity around better educating patients about what trials are out there. If your disease happens to have advocacy groups, organized advocacy groups, that's a tremendously helpful way to find out about what kind of clinical trials might be happening. You know, AI and and Google, they're at our fingertips now. So it's probably easier to find a clinical trial than it ever has been before, but it's still a lot to navigate, especially if you're in a condition where you might have many options for for participation, trying to decide which one is best for you. That's a conversation that you need to have with your doctor for sure.

unknown 21:30

Yeah.

SPEAKER_00 21:30

Well, especially most electors. The research shows that patients want to hear about clinical trial opportunities from their doctors, but only about 15% of physicians really understand clinical trials, have participated or referred patients into trials. So that means that 85% don't. And so we uh in the industry actually do a lot of advertising as well. So you might see ads pop up either on Google or Facebook or Reddit looking for. Patient volunteers for clinical research as well. Some of the ads are good and some are really bad. So, you know, even here in Boston, you can see Mass General advertises on the T, which is our subway system. So a lot of times New York too. Yeah, a lot of times the industry needs to supplement what we call known patients. So no uh patients who are known to the doctors who are participating in the study with patients that we find in the greater community.

SPEAKER_01 22:27

Okay, that's that's really helpful. Okay, and now someone's enrolled. Okay, Mindy, this is back to you. So now what happens? Like what is the what is going on day to day? What does participation look like? And I know you you your experiences with it as the parent.

SPEAKER_02 22:42

So when I first entered the space, we didn't have that many clinical trials going on and the indication that that is affecting my family. And back then we were it was almost competitive to try to get into a trial. Now I think patients are a lot more savvy about what the expectations are to participate, but I think there's still a lot of education that needs to happen. When you enter into a clinical trial, you also have a responsibility to meet the the you know the operating procedures of the trial. You have to show up, you have to be at clinic, you have to usually visit clinic within a window of time. It's usually only a few days. These are set schedules. So there's a lot of responsibility on the patient's part too. I think the burden of participation might not seem so bad at first, but then as you roll into month six, month nine, month twelve, you start really kind of getting, you can get trial fatigue. Um there's a lot of a lot of great work happening about trying to make that a little bit easier, sharing information about your trial visit with your healthcare practitioners so you can kind of cut down on because a lot of these patients are seeing their their doctors often too, because they're sick. They have a condition. So they've got this big big part of their life is dealt dealing with their own medical health. So to ask them to participate in a trial is really piling on a lot of time. And, you know, sometimes these conditions are life limiting. Patients don't feel like they have a lot of time and they don't want to spend their time at it at in the clinics. So participating in a clinical trial is is a big time suck. And you have to really take that seriously and think about how it's gonna fit into your life. If you're if you're working, if you've got young kids, if you've got elderly parents you have to be taking care of, if there's travel involved, travel's a huge one. How uh how far are you gonna have to go? Sometimes in rare disease, you're getting on an airplane to go to a clinical trial site.

SPEAKER_01 24:35

That's a heavy burden.

SPEAKER_02 24:36

There's a lot involved, and patients really have to think about how participation is gonna fit into their life.

SPEAKER_01 24:44

Thank you. That was really helpful. And I know we could continue on this part of the this part of the episode like for hours and hours and hours, and I hate to cut it short, but I do want to get to the second part. So I'm gonna ask one last question on this part. I mean, so much good comes out of trials, right? I mean, all of the medicines we have, the devices we have have have gone through trials, but people are still very nervous about them. What's what what scares people the most about trials? Well, there's a lot of distrust.

SPEAKER_02 25:09

I mean, I think I think that's that's something that we're that I thought maybe was improving after the pandemic, but it's it's kind of back now to maybe even below square one. I think there's probably more distrust about pharmaceuticals and trials than maybe ever. It's scary. I mean, so and sometimes when you're when you're thinking about really big jump ahead in technology, I'm I work in a space where we have a lot of gene and cell therapy activity. Gene therapies are hopefully one-time fixes and not cures. They're certainly not cures. Some maybe some of them are better than others, but you know, you you are taking a risk. You have to always benefit we talk about benefit risk a lot. You know, you've got to weigh, and everybody's different on how they weigh it, the the potential benefits to you versus what you're risking. And that can be a risk of your time, your health, or your life.

SPEAKER_01 26:03

Those are legitimate reasons to be nervous. Kelly, what also, but historically there have been challenges with trials, right?

SPEAKER_00 26:09

I mean, yes, there have been bad things that have happened in the past. There are laws and regulations to protect patients now that must be followed and are followed. Also, you know, the media sensationalizes some things, right? You know, if you watch Grey's Anatomy, not recently, because they have done a better job recently, but back back, I don't know, 10 years or so, every time a clinical trial was mentioned, it involved talking about people like guinea pigs or something, you know, bad happened, or somebody died, or something like that. And and now, you know, for those of us who have stuck with that program for as long as it's been on, you are seeing clinical trials being shown in a better light. And so, you know, bad stories travel faster than good stories. I would love to see the industry do more stories on the benefits of participating, the people who are benefiting from clinical trials, being able to meet people who actually were in clinical trials, because they're the reasons that, you know, new medicines are made. So I'm still hopeful for the future, but uh we still have a long way to go. Better marketing.

SPEAKER_02 27:22

Yeah, and talk talking to patients, I think that's a great point, Kelly, talking to patients about their experience, especially if they're they're good experiences and and honoring the patients. You know, we hear so much about these heroic doctors and researchers, and they are. They win prizes, they win Nobel prizes, and they win all kinds of scientific awards, but the patients are actually the reason why these trials can even happen. So I would love to see, especially when when you are working in a condition that is life-limiting, and the people that participated in trials to kind of get you to where, to get the field to where it is, a lot of those patients are gone. Their families are still here, though. And and I think there's a legacy that patients leave behind when they participate. And it can be one of the best things that you can do with your life, honestly. Some of these diseases we would be nowhere if we hadn't had the participants.

SPEAKER_01 28:09

So more stories, more patient-centric stories, better marketing and communication.

SPEAKER_00 28:15

Yeah. Yeah.

SPEAKER_01 28:16

That'll be a great place to start.

SPEAKER_00 28:18

We need to design trials that are better for patients.

SPEAKER_01 28:20

Okay, so that was a perfect thank you, Kelly. That was a perfect segue into part two. Thanks for joining us for this week's edition of Rupture, the world of best guesses stand. Today's episode took us inside a clinical trial and featured Kelly McKee and Mindy Cameron. To hear more stories and to support our work, the best way is to subscribe to our YouTube channel. Until next time.