Understanding Clinical Trials

Understanding Clinical Trials 

For Release Sept. 24, 2024

 

PODCAST OPEN:      

You’re listening to the Live Yes! With Arthritis podcast, created by the Arthritis Foundation to help people with arthritis — and the people who love them — live their best lives. This podcast and other life-changing resources are made possible by gifts from donors like you. If you’re dealing with chronic pain, this podcast is for you. You may have arthritis, but it doesn’t have you. Here, learn how you can take control of arthritis with tips and ideas from our hosts and guest experts.

 

This Pain Awareness Month episode of the Live Yes! With Arthritis podcast is brought to you in part by Aleve, up to 12 hours of pain relief.

 

MUSIC BRIDGE

 

Christina Schaefer:

Hi, welcome to the Live Yes! With Arthritis podcast. I'm Christina Schaefer, your host for this episode. I was diagnosed with rheumatoid arthritis about 19 years ago and have been dealing with the ups and downs of living with this disease ever since.

 

Clinical trials provide invaluable insights into the prevention, detection and treatment of chronic conditions like arthritis. In fact, they're the primary way researchers find out if a new treatment, like a new drug, diet, type of exercise, behavioral therapy or medical device, such as a pacemaker, is effective for people. But what exactly is a clinical trial? How do trials work? What happens when there's multiple phases of trials? What role does the FDA play? And as patients with arthritis, how and should we participate in clinical trials? In this episode of the Live Yes! With Arthritis podcast, we aim to answer some of these and other questions about this research method and help unlock some of the mystery.

 

Today, I'm joined by Travis Salmon, an osteoarthritis patient who participated in a clinical trial for OA of the lower extremities, and Paul Larkin, PhD, vice president of science for the Arthritis Foundation. Travis and Dr. Larkin, welcome to the podcast.

 

Travis Salmon:

Thank you, Christina, thanks for having me.

 

Dr. Paul Larkin:

Happy to be here.

 

Christina Schaefer:

Travis, tell us a little bit about yourself and your experiences with arthritis.

 

Travis Salmon:

I was diagnosed with end-stage osteoarthritis in my left ankle in 2002 when I was about 27 or 28 years old. The arthritis was due to several severe ankle sprains that I had whenever I was playing basketball in high school and in college. Unfortunately, I didn't take care of those ankle injuries the way I should have. My goal at the time was just to, you know, get back out on the court. I suffered the consequences several years after my college playing days were done. I noticed that my ankle was swollen and stiff, and it continued to get worse.

 

When I was diagnosed, I remember the doctor telling me that I'd have to have an ankle fusion at some point in my life. And it terrified me. So, I spent the next 16 years essentially trying to prove that doctor wrong. I did everything that I could think of in that time period, from prescription medications, bracing, various types of physical therapy, E-stim, acupuncture, injections, natural remedies, supplements.

 

Even though I had seven surgeries, from minor arthroscopes to complete ankle reconstruction during that time period, I went from coast to coast trying to find a solution, from getting fitted to something called an ExoSym device, which functioned like a prosthetic; I went to the East Coast where I had stem cell therapy done. Nothing seemed to work. My ankle got worse during this time period to the point that it was really difficult to walk.

 

In 2018 I felt like I'd exhausted all of the sort of reasonable options. So, I decided to have the ankle fusion, and it was a long, long recovery. But it worked. For the past several years, I've lived with essentially no pain in my left ankle, and I've got my life back. And it's been just a wonderful thing for me and for my family.

 

Christina Schaefer:

Thank you so much for being here, Travis, and sharing your story with us. Dr. Larkin, tell us a little bit about yourself and your experience as it relates to arthritis and clinical trials.

 

Dr. Paul Larkin:

Sure. So, I'm a neuroscientist by training. I studied sort of basic science as a grad student and a postdoc. But then after that, I worked as a regulatory consultant for a while, which is where we consult with companies that are developing new drugs about how best to interact with the FDA during that process. And then I moved to some other aspects of commercialization for a while before joining the nonprofit world a couple of years ago, with a few different nonprofits. And of course, that's a different perspective on clinical trials again, where we really get involved in understanding what clinical trial participation means to the participants and their values in that process as well. So that's a second education in clinical trials for me.

 

I'm now at the Arthritis Foundation leading our science team, where we focus primarily on funding external research, some of which is clinical, some of which is not, and also on bringing experts together to discuss the future of arthritis research.

 

Christina Schaefer:

Thank you so much. Let's start simple: What exactly is a clinical trial and how does it compare to other research studies? I think we can start with you on this one, Travis.

 

Travis Salmon:

For the clinical trial, it was really an opportunity for me. It was obviously in a clinical setting at a hospital. It was an opportunity to try to find a sort of a remedy or solution to my arthritis. It was working with my health care team to go through the potential benefits and talk about the risks and understand what a positive outcome could look like. And knowing that it was a trial; it was something that was not guaranteed to work.

 

Christina Schaefer:

Dr. Larkin?

 

Dr. Paul Larkin:

I'll speak sort of generally and just say as a definition that a clinical trial is a research study involving human volunteers, where those volunteers, who are also known as participants, often are assigned to groups that receive one or more interventions — so that the researchers involved can evaluate the effects of those interventions on biomedical or health-related outcomes.

 

Most of the time when we're thinking about clinical trials, we're thinking about potential new drugs, and so that drug or the drug candidate is the intervention that's being tested in the trial. But certainly other clinical trials can test things like diagnostics or surgical interventions or new ways of making decisions in clinical practice — all of which count as interventions that can impact clinical care. And where clinical trials are really the absolute best way to get as much information as possible about whether or not that intervention is going to be effective for patients; and whether or not, in particular, the benefit-risk ratio of that intervention is a positive one.

 

Christina Schaefer:

Why are clinical trials so vital?

 

Dr. Paul Larkin:

One is just that if you want to get a new drug approved by the FDA, which is the way that that drug can get to the patients who need it, you need to run a clinical trial, because the FDA requires clinical trials of new drugs. And so, for new drugs, you do need clinical trials to understand the cost-benefit ratio, to see whether or not it's one that is beneficial for patients, or beneficial for certain patients, or more or less beneficial than other treatments that are available.

 

Christina Schaefer:

Travis, from the patient perspective, why do you feel that clinical trials are so vital?

 

Travis Salmon:

My clinical trial that I participated in didn't involve necessarily drugs or new medications, so it's a bit different than some of the clinical trials that are out there. It was an opportunity to be a part of something that, they were hopeful, could be another treatment option, rather than the finality of an ankle fusion. If this type of trial has success, if patients receive the benefits that they were hopeful that they would receive, this could be another option, another tool, that patients like me, moving forward, could use.

 

Christina Schaefer:

Dr. Larkin, how exactly does a clinical trial work? And what are the different phases of that clinical trial?

 

Dr. Paul Larkin:

It's important to maybe take a step back and talk about clinical development as a whole. A given clinical trial will generally be described as either phase one, phase two or phase three. And so, for a given intervention like a new drug, it'll have to go through phase one trials first and succeed there; move to a phase two trial, succeed there; move to a phase three trial, succeed there. And then go put all that data together into an application that'll go to the FDA for approval. That whole process takes many years, something on the order of 10 years. And each step along the way is a risky one and is unique in its own way.

 

Generally speaking, a phase one trial is your first step. It's the first time an intervention is really being tested in humans. And that trial is smaller, it's quicker and it's really focused on safety rather than finding out whether or not the drug works. If that's successful, if you can find a dose of the drug that is predicted to be efficacious and is shown to be safe by the phase one trial, then you can move to the phase two trial, where you're starting to try and understand efficacy and trying to get a look at that, in addition to testing the drug in a larger group of participants, to get a better look at safety. That phase two step is often the riskiest in the process, not necessarily in terms of risk to the participants, but just risk to the development program. More programs fail in phase two than in other phases of drug development.

 

But if you do have a successful phase two trial that provides some evidence of efficacy and continues to show evidence of safety, then you move to a large phase three trial. Those are your largest trials — largest, longest, most expensive, most involved trials. And there, you're really expanding the patient population to one that's reflective of how the drug would be used if it were approved. And you're looking for really concrete evidence of efficacy, along with continued evidence of safety in that broader population.

 

And then, of course, if that's successful, then finally you put all that data together, along with all the data that led to the development of the drug in the first place — the cellular and animal models, whatever it was along the way — and present that to the FDA and ask them to adjudicate on the cost-benefit ratio, the safety-to-efficacy ratio of the entire application package, and make a decision on whether or not that that new drug can be marketed in the U.S.

 

Christina Schaefer:

What role does the FDA play in all of this?

 

Dr. Paul Larkin:

They're involved throughout the process. They're consulting with the people who are developing the drug, around how best to run a trial, around how best to interpret the results. What does it mean to be safe in this context, in this disease? So, they're involved throughout clinical development. Mostly the public spotlight is on them when you get to that last step around approval, but that's certainly not the first time they've seen some of this data. And they're a very important partner for all of us. It's really important for the FDA to stay up to date on what's going on and the evolving understanding of biology that underlies these new drugs. And so that's a big part of what they do.

 

PROMO:

Want to help grow our movement and conquer arthritis as a volunteer? There are lots of ways to get involved with the Arthritis Foundation and make an even greater difference. To get going, check out arthritis.org/volunteer.

 

Christina Schaefer:

Are clinical trials safe?

 

Dr. Paul Larkin:

Well, there's always some risk in a clinical trial. You're doing something new, and it's something that is a test, and so we don't know what the results are going to be. So, there's always some risk, and it's important to keep that in mind. I think any individual who is considering involvement in a clinical trial should explore both personally and with their physicians and with anyone who is running the trial: What's known about the agent that's being tested and what the potential risks may be. What the potential burdens of the trial may be as well, because I think that's another aspect of it, is that the sponsors that are running clinical trials know that there is risk involved. And they're doing everything that they possibly can to mitigate that risk.

 

Because a drug company that is testing a new drug, they have a lot invested in a positive outcome as well, and so they want to make sure that the risks are controlled as best they can be. And that extends as well to the clinicians who are running the study. They have an added incentive to really pay attention to any changes in the health of a participant, and so they and the sponsors are working together to make sure that the risks are monitored and that they have a plan in place for responding to any adverse events that may show up.

 

The quality of care that participants get during a clinical trial is generally quite high, and that makes sense, because there is the possibility of risk during that clinical trial. How you think about the benefit of a trial is really what's going to dictate your decision on whether or not to join a trial. And so, I like Travis's point about the benefits of a clinical trial are not just around that specific agent or your specific arthritis. It's about contributing to research in general. Risk is always involved, but there is certainly benefit, too. I think those benefits are really high, but I don't want to discount the risks either.

 

Christina Schaefer:

And for you, Travis, as far as safety is concerned, I'm sure there was a period of weighing the pros and cons. What ultimately inspired you to take that risk and to participate in a clinical trial?

 

Travis Salmon:

An important part of my decision was to communicate and work with my health care team to talk about the risks, to talk about the potential benefits, for me and for other patients. I feel like I went into this clinical trial having a good understanding of what those things were: the time commitment, the financial commitment, all of those things were factors for me. There are risks with, in my case, a surgical procedure. But I felt comfortable with my health care team, that I was in good hands.

 

Christina Schaefer:

Tell us about your experiences. Tell us the good, the bad and everything in between.

 

Travis Salmon:

The clinical trial that I participated in was conducted at the University of Iowa in Iowa City. I think there were maybe ultimately a hundred or maybe up to 200 patients that were part of this clinical trial. And it was conducted by the health care team and providers at that location and that clinic. The study involved a procedure where an external fixator was placed onto the lower leg, essentially from right below my knee all the way down to my foot, which separated the ankle joint for a three-month period of time, I think by about five millimeters, so not much.

 

The hope was that there could be some short-term and long-term benefits related to the body sort of being allowed to potentially generate cartilage, like protection in that joint, during that three-month period of time. There were, I believe, two control groups in the study: one group that had a micro fracture procedure done along with the placement of the external fixator; and one group that didn't.

 

I underwent the procedure in late 2006, which included the surgeons installing this external fixator on my lower leg, which essentially looks like a halo. It had, I think, 17 or 18 different sorts of bolts and pins that were attached to my shin, all the way down to below my foot. I was able to weight-bear for part of that three-month period of time. At the end of that three months, another outpatient procedure was done to remove the fixator.

 

For two years afterwards, I was required to travel back to Iowa City. I live in the Kansas City area, so a four- or five-hour drive. I think I traveled there for maybe eight or 10 times during that period of time for follow-up testing, evaluations, that sort of thing. And ultimately for me, the clinical trial, the procedure, worked for a while to reduce some of the pain that I was having, but it wore off.

 

So, after about, I would say two or three years, the relief kind of subsided and the pain returned. It wasn't the long-term benefit that I was hopeful for. But I feel like this was an important part of a potential treatment option for patients with osteoarthritis. I still remain happy that I was involved with it and happy that I went through it. While it didn't work for me, ultimately, I feel like this was an important part of my journey with arthritis.

 

PROMO:

An arthritis diagnosis can be overwhelming — learning about your disease, getting started on new medications and making lifestyle changes. But there are plenty of steps you can take to manage arthritis, regain control and get back to doing the things you love. Get tips at arthritis.org/newly-diagnosed.

 

Christina Schaefer:

Dr. Larkin, Travis mentioned that there were many people involved in the clinical trial he participated in. Why is it so important to have so many participants in a clinical trial?

 

Dr. Paul Larkin:

The more people you have, the better your understanding of whether or not the intervention works. If the trial had two people in it, and one of them got the drug and the other didn't, you wouldn't really be able to know if any difference in outcomes is due to the difference that one of them received the drug and one didn't, or just some other difference between those two people. And that continues to be true with small studies. And so, the larger the study is, the better you're able to control for differences between the participants that receive the intervention and the participants that don't.

 

There is certainly a whole branch of clinical trial design that's devoted to figuring out the right number of people for a clinical trial, because you want to give yourself the best chance of seeing a real effect, if there is one there, or convincing yourself that there's not an effect if there is indeed not an effect, without asking too many people to join the trial. Because, of course, that's a big investment of their time. It's a risk, as we've discussed, for all of them. It's a big investment for all the people involved in working on the trial. And it's a lot of time and money to pay for the trial as well. So, I think trials are large because that's the way to get the amount of evidence that's necessary to really convince us one way or the other.

 

Christina Schaefer:

How can patients find a clinical trial that is right for them?

 

Dr. Paul Larkin:

There are a couple of resources. Certainly, one place that you can look for more information is our site at arthritis.org/clinicaltrials. You can find our clinical trial finder. The other resource that is commonly used, I think, is clinicaltrials.gov, and so that's obviously a government-sponsored site that lists essentially all the clinical trials that are happening in the U.S. and are available. And it includes a large number of international trials as well.

 

The trial finder on our site is one that hopefully addresses one of the big shortcomings of clinicaltrials.gov, which is that it's a pretty complicated site. Clinicaltrials.gov allows you a lot of control in terms of what you're looking for and how you're looking, and it gives you a lot of information about the trials themselves as well. But it has so many options that it can be a little bit overwhelming. And so, the one on our site uses the same information, but hopefully presents it in a little more understandable format. Always discuss trials that you're considering with your own physician. They'll certainly have opinions or have recommendations on who else to talk to about that.

 

Christina Schaefer:

Travis, from a patient perspective, how important would it be to you to see that a clinical trial's listed on the arthritis website or the clinicaltrials.gov website?

 

Travis Salmon:

I'd want to know as much about it as possible. I sort of lucked into this clinical trial that I participated in, because the health care team that I was working with was actually conducting this clinical trial, so I didn't have to go far. I talked with the health care team in Iowa City. I talked with the local physician who I had worked with in the past about this trial. I consulted with the Arthritis Foundation because I was working with the Arthritis Foundation at the time as a volunteer. I really wanted to know whether this was right for me. What Dr. Larkin said is absolutely right. Consulting with your physicians, using these resources, is really, really crucial to figuring out whether it's right for you.

 

Christina Schaefer:

Travis, what other key things would you encourage listeners to keep in mind when it comes to clinical trials?

 

Travis Salmon:

Some of those things would include the financial commitment. For me, there were out-of-pocket costs involved, including travel costs, but also the time commitment. I know clinical trials vary widely in terms of time commitments, but for me there was a significant time commitment. What would the recovery look like? What would that three-month period of time when I had that big halo on my lower leg look like? What would I be able to do? What couldn't I do? How would that affect work?

 

Those, I think, are really important considerations and factors. And they're going to differ from patient to patient, from clinical trial to clinical trial. How they'd affect you, how they'd affect your family, your employer, all of those things I think are really important factors to consider.

 

Christina Schaefer:

Dr. Larkin, the out-of-pocket expenses and the travel expenses, is that common? Or do you find that those are typically covered in these clinical trials?

 

Dr. Paul Larkin:

I think it varies quite a bit. That's something that you would need to look into for an individual trial. I think there are often additional costs. Maybe there's an additional visit; maybe there's an additional type of assessment that needs to be done, something like that. The question is whether or not the sponsor covers those costs. And sometimes they cover them to some degree. Sometimes they cover them completely. Sometimes they aren't able to cover them at all. It's a crucial question when you're evaluating your decision on whether or not to participate, for sure.

 

PROMO:

The Arthritis Foundation is always looking for new ways to inform you about the things you want to know more about. Check out our webinars — in real time or on demand. Visit arthritis.org/webinars to learn more.

 

Christina Schaefer:

Before each episode, we post a question on social media. For this episode, we asked: “What's the best or worst experience you have had participating in a clinical trial?” Now, we got a few responses, but the most notable was from De Purple Player, who said their worst experience included “getting the placebo.” And I think that's a common fear among patients. What are your thoughts on that? We'll go with you first, Dr. Larkin.

 

Dr. Paul Larkin:

I'm sure that is a really frustrating experience for a lot of people in clinical trials, to be committing so much time and effort to a trial and not seeing improvement. But at the same time, I would say a couple of things. One is that just, unfortunately, placebos are necessary in clinical trials. You have to be able to compare between people who are receiving the intervention and people who are not receiving the intervention in order to know if the intervention works. And so, it's a frustrating but necessary piece of clinical trials. And I'm sure participants know that, because you are joining a trial where part of the goal is to contribute to the advancement of knowledge in the field of arthritis research in general.

 

Even in the placebo group, your contributions are still incredibly valuable for the research and for even the development of that particular drug. I do want to point out that it is possible to leave a clinical trial. If you really feel like you are on the placebo and therefore your health is deteriorating, you can absolutely work with your physician and work with the sponsor of the trial to leave that trial and go back to whatever other standard of care you were on before.

 

A lot of clinical trials are specifically designed with that understanding in mind, knowing that participants may want to leave, or may experience, you know, something like a flare, an increase in inflammation, that leads to them having a need to use an additional medication that's outside of the study protocol, or something like that. And so, it is a frustrating experience, but it is part of clinical trials, and it is something where hopefully some of the frustration can be mitigated, both by the fact that your physician, your care team, can help you deal with that on a sort of health care basis, and by the fact that your participation is still supremely valuable to the clinical trial itself.

 

Christina Schaefer:

Travis, you have anything you want to add there?

 

Travis Salmon:

My clinical trial didn't involve a placebo, but there were two control groups. I was really, really, really hoping, going into this, that I would be part of that control group that would get the micro fracture, sort of an additional treatment. Unfortunately, I wasn't in that group, so I was really bummed. But to Dr. Larkin's point, it's part of the clinical trial. And one of the great things that I think I did was: I really explored that. I wanted to know what the potential advantages of that micro fracture would be. What would it look like if I wasn't part of that group? I was sad about it, but I knew that going in. And I accepted that sort of risk. I just made the best of it.

 

Christina Schaefer:

I think for different patients, you know, there might be different perspectives. As someone who has rheumatoid arthritis, I can't see myself stopping a treatment that's working for me to participate in a clinical trial. But there was a point where I had gone down the list of medications with my doctor, we tried six, seven medications, nothing was working, and we were getting down to the end of the list. And there was a brand-new medication that had just gotten FDA approval, and he said, "Do you want to try this, or should we start looking at some clinical trials?" And luckily, that medication has been working for me for a few years now.

 

If a patient does reach the end of that list of medications and nothing is working, at least they could try something. And even though they might end up with a placebo, they're likely already in pain. So, it's kind of, again, weighing the pros and cons.

 

To close each episode, we typically share our top three takeaways from the episode. So, we’ll start with you, Travis.

 

Travis Salmon:

To me, a lot of this boils down to getting as much information as you can to make the best decision that you can. I would encourage others, like I did, to research, research, research. Understand the purpose, the potential outcomes. What are the risks? Will this clinical study eliminate or prohibit other potential treatment options that might be available now or down the road? Does it work for you and your family from a time and financial commitment perspective?

 

It's also for me about communication. Communicating with your health care team and providers, to learn about those risks, about the benefits, the costs, other important factors. And I think also importantly, to communicate your goals, your objectives, with your team, to make sure that that entire team is on the same page. Communicating with your inner circle, whoever that may be — your family, your friends — because, like me, you will likely need them with this clinical study for a lot of reasons. And I think the third thing for me, the takeaway would be: This clinical study that I participated in illustrates, I think, my goal of not letting this disease get the best of me.

 

It was an important part of my journey with arthritis. While it ultimately didn't provide the long-term benefits that I was looking for, I do consider it a success in terms of my approach with this disease. I was not willing to accept that I was going to be in pain for the rest of my life. And it was another important step that I took to know that I exhausted all other options before I decided to have my ankle fusion. And so, my hope is that others will be able to use clinical studies to obtaining relief for whatever objectives they have in beating arthritis. Those are some of my key takeaways.

 

Christina Schaefer:

Dr. Larkin, what are your top three takeaways from today?

 

Dr. Paul Larkin:

I think those were great, Travis. I would say that for me, number one is just that clinical trials are the best way to advance knowledge about new treatments, and they're really the only way to get new treatments approved. They're tremendously important and tremendously valuable. That said, I think the second takeaway for me is just that there are definitely risks of participating in clinical research and there are burdens to participating in a given clinical trial, whether that's time or money or effort. And I think with those two in mind, the third point is just that it means that this is a really complex decision of whether or not to participate in a given clinical trial.

 

Communication is key, and looking for information across a number of sources, and knowing that there are a lot of sources out there for you, including certainly your physician and care team. And the sponsor of the trial is going to be an organization that's putting out a lot of information about what the trial is designed to do. All those entities really want to help you with that decision and want to provide as much information as you need to make that decision. I think you should always take advantage of that to the fullest, and always feel free to ask as many questions, any questions, that come to mind when making that complex decision. So, I think that's it for me.

 

Christina Schaefer:

For me, my top three takeaways… The biggest one was: Do your research. You both gave great points about researching and finding out as much as you can about the clinical trial. Having an open conversation with your doctor or health care team, really diving into what this means for you and your treatment. And your future, potentially. And then of course, weighing the pros and cons for yourself and deciding if this clinical trial is the best way to go. Those were my top three takeaways.

 

I feel like today's conversation was excellent. And it can be a really great guide to those who are interested in clinical trials. Thank you both for your time today and sharing your stories and your knowledge.

 

Travis Salmon:

Thanks, Christina. Thanks, Dr. Larkin. This was great.

 

Dr. Paul Larkin:

I agree. Great to be here with both of you. Thanks.

 

Christina Schaefer:

For more information on clinical trials, visit arthritis.org/clinicaltrials. And for more arthritis resources, visit arthritis.org.

 

PODCAST CLOSING:

The Live Yes! With Arthritis podcast is independently produced by the Arthritis Foundation. Gifts from people like you make our podcast and other life-changing resources possible. You can donate at arthritis.org/donate. This podcast aims to help people living with arthritis and chronic pain live their best life. For a transcript and show notes, go to arthritis.org/podcast. Subscribe, rate and review us wherever you get your podcasts. If you subscribe through Spotify, leave a comment on their platform, letting us know what you think about this episode. And stay in touch!