Understanding Clinical Trials

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Understanding Clinical Trials 

For Release Sept. 242024

 

PODCAST OPEN:      

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MUSIC BRIDGE

 

Christina Schaefer:

Hiwelcome to the Live Yes! With Arthritis podcast. I'm Christina Schaeferyour 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 preventiondetection and treatment of chronic conditions like arthritis. In factthey're the primary way researchers find out if a new treatmentlike a new drugdiettype of exercisebehavioral therapy or medical devicesuch as a pacemakeris 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 arthritishow and should we participate in clinical trials? In this episode of the Live Yes! With Arthritis podcastwe aim to answer some of these and other questions about this research method and help unlock some of the mystery.

 

TodayI'm joined by Travis Salmonan osteoarthritis patient who participated in a clinical trial for OA of the lower extremitiesand Paul LarkinPhDvice president of science for the Arthritis Foundation. Travis and Dr. Larkinwelcome to the podcast.

 

Travis Salmon:

Thank youChristinathanks for having me.

 

Dr. Paul Larkin:

Happy to be here.

 

Christina Schaefer:

Travistell 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. UnfortunatelyI didn't take care of those ankle injuries the way I should have. My goal at the time was just toyou knowget 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 stiffand it continued to get worse.

 

When I was diagnosedI remember the doctor telling me that I'd have to have an ankle fusion at some point in my life. And it terrified me. SoI spent the next 16 years essentially trying to prove that doctor wrong. I did everything that I could think of in that time periodfrom prescription medicationsbracingvarious types of physical therapyE-stimacupunctureinjectionsnatural remediessupplements.

 

Even though I had seven surgeriesfrom minor arthroscopes to complete ankle reconstruction during that time periodI went from coast to coast trying to find a solutionfrom getting fitted to something called an ExoSym devicewhich 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. SoI decided to have the ankle fusionand it was a longlong recovery. But it worked. For the past several yearsI've lived with essentially no pain in my left ankleand 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 hereTravisand sharing your story with us. Dr. Larkintell us a little bit about yourself and your experience as it relates to arthritis and clinical trials.

 

Dr. Paul Larkin:

Sure. SoI'm a neuroscientist by training. I studied sort of basic science as a grad student and a postdoc. But then after thatI worked as a regulatory consultant for a whilewhich 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 agowith a few different nonprofits. And of coursethat's a different perspective on clinical trials againwhere 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 teamwhere we focus primarily on funding external researchsome of which is clinicalsome of which is notand 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 oneTravis.

 

Travis Salmon:

For the clinical trialit 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 volunteerswhere those volunteerswho are also known as participantsoften 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 trialswe're thinking about potential new drugsand 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 notin particularthe 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 FDAwhich is the way that that drug can get to the patients who need ityou need to run a clinical trialbecause the FDA requires clinical trials of new drugs. And sofor new drugsyou do need clinical trials to understand the cost-benefit ratioto see whether or not it's one that is beneficial for patientsor beneficial for certain patientsor more or less beneficial than other treatments that are available.

 

Christina Schaefer:

Travisfrom the patient perspectivewhy 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 medicationsso 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 thatthey were hopefulcould be another treatment optionrather than the finality of an ankle fusion. If this type of trial has successif patients receive the benefits that they were hopeful that they would receivethis could be another optionanother toolthat patients like memoving forwardcould use.

 

Christina Schaefer:

Dr. Larkinhow 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 onephase two or phase three. And sofor a given intervention like a new drugit'll have to go through phase one trials first and succeed there; move to a phase two trialsucceed there; move to a phase three trialsucceed 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 yearssomething on the order of 10 years. And each step along the way is a risky one and is unique in its own way.

 

Generally speakinga phase one trial is your first step. It's the first time an intervention is really being tested in humans. And that trial is smallerit's quicker and it's really focused on safety rather than finding out whether or not the drug works. If that's successfulif you can find a dose of the drug that is predicted to be efficacious and is shown to be safe by the phase one trialthen you can move to the phase two trialwhere you're starting to try and understand efficacy and trying to get a look at thatin addition to testing the drug in a larger group of participantsto get a better look at safety. That phase two step is often the riskiest in the processnot necessarily in terms of risk to the participantsbut 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 safetythen you move to a large phase three trial. Those are your largest trials — largestlongestmost expensivemost involved trials. And thereyou'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 efficacyalong with continued evidence of safety in that broader population.

 

And thenof courseif that's successfulthen finally you put all that data togetheralong with all the data that led to the development of the drug in the first place — the cellular and animal modelswhatever it was along the way — and present that to the FDA and ask them to adjudicate on the cost-benefit ratiothe safety-to-efficacy ratio of the entire application packageand 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 drugaround how best to run a trialaround how best to interpret the results. What does it mean to be safe in this contextin this disease? Sothey're involved throughout clinical development. Mostly the public spotlight is on them when you get to that last step around approvalbut 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 goingcheck out arthritis.org/volunteer.

 

Christina Schaefer:

Are clinical trials safe?

 

Dr. Paul Larkin:

Wellthere's always some risk in a clinical trial. You're doing something newand it's something that is a testand so we don't know what the results are going to be. Sothere's always some riskand 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 wellbecause I think that's another aspect of itis 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 drugthey have a lot invested in a positive outcome as welland 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 participantand 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 highand that makes sensebecause 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 soI 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 involvedbut there is certainly benefittoo. I think those benefits are really highbut I don't want to discount the risks either.

 

Christina Schaefer:

And for youTravisas far as safety is concernedI'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 risksto talk about the potential benefitsfor 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 commitmentthe financial commitmentall of those things were factors for me. There are risks within my casea surgical procedure. But I felt comfortable with my health care teamthat I was in good hands.

 

Christina Schaefer:

Tell us about your experiences. Tell us the goodthe 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 legessentially from right below my knee all the way down to my footwhich separated the ankle joint for a three-month period of timeI think by about five millimetersso 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 cartilagelike protection in that jointduring that three-month period of time. There wereI believetwo 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 2006which included the surgeons installing this external fixator on my lower legwhich essentially looks like a halo. It hadI think17 or 18 different sorts of bolts and pins that were attached to my shinall 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 monthsanother outpatient procedure was done to remove the fixator.

 

For two years afterwardsI was required to travel back to Iowa City. I live in the Kansas City areaso 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 testingevaluationsthat sort of thing. And ultimately for methe clinical trialthe procedureworked for a while to reduce some of the pain that I was havingbut it wore off.

 

Soafter aboutI would say two or three yearsthe 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 meultimatelyI feel like this was an important part of my journey with arthritis.

 

PROMO:

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

 

Christina Schaefer:

Dr. LarkinTravis 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 havethe better your understanding of whether or not the intervention works. If the trial had two people in itand one of them got the drug and the other didn'tyou 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'tor just some other difference between those two people. And that continues to be true with small studies. And sothe larger the study isthe 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 trialbecause you want to give yourself the best chance of seeing a real effectif there is one thereor convincing yourself that there's not an effect if there is indeed not an effectwithout asking too many people to join the trial. Becauseof coursethat's a big investment of their time. It's a riskas we've discussedfor 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. SoI 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. Certainlyone 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 usedI thinkis clinicaltrials.govand 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.govwhich 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 lookingand 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 sothe one on our site uses the same informationbut 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:

Travisfrom a patient perspectivehow 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 inbecause the health care team that I was working with was actually conducting this clinical trialso 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 physiciansusing these resourcesis reallyreally crucial to figuring out whether it's right for you.

 

Christina Schaefer:

Traviswhat 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 methere were out-of-pocket costs involvedincluding travel costsbut also the time commitment. I know clinical trials vary widely in terms of time commitmentsbut 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?

 

ThoseI thinkare really important considerations and factors. And they're going to differ from patient to patientfrom clinical trial to clinical trial. How they'd affect youhow they'd affect your familyyour employerall of those things I think are really important factors to consider.

 

Christina Schaefer:

Dr. Larkinthe out-of-pocket expenses and the travel expensesis 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 donesomething 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 participatefor 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 episodewe post a question on social media. For this episodewe asked: “What's the best or worst experience you have had participating in a clinical trial?” Nowwe got a few responsesbut the most notable was from De Purple Playerwho 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 firstDr. Larkin.

 

Dr. Paul Larkin:

I'm sure that is a really frustrating experience for a lot of people in clinical trialsto be committing so much time and effort to a trial and not seeing improvement. But at the same timeI would say a couple of things. One is that justunfortunatelyplacebos 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 soit's a frustrating but necessary piece of clinical trials. And I'm sure participants know thatbecause 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 groupyour 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 deterioratingyou 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 mindknowing that participants may want to leaveor may experienceyou knowsomething like a flarean increase in inflammationthat leads to them having a need to use an additional medication that's outside of the study protocolor something like that. And soit is a frustrating experiencebut it is part of clinical trialsand it is something where hopefully some of the frustration can be mitigatedboth by the fact that your physicianyour care teamcan help you deal with that on a sort of health care basisand by the fact that your participation is still supremely valuable to the clinical trial itself.

 

Christina Schaefer:

Travisyou have anything you want to add there?

 

Travis Salmon:

My clinical trial didn't involve a placebobut there were two control groups. I was reallyreallyreally hopinggoing into thisthat I would be part of that control group that would get the micro fracturesort of an additional treatment. UnfortunatelyI wasn't in that groupso I was really bummed. But to Dr. Larkin's pointit'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 itbut 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 patientsyou knowthere might be different perspectives. As someone who has rheumatoid arthritisI 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 doctorwe tried sixseven medicationsnothing was workingand we were getting down to the end of the list. And there was a brand-new medication that had just gotten FDA approvaland he said"Do you want to try thisor should we start looking at some clinical trials?" And luckilythat 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 workingat least they could try something. And even though they might end up with a placebothey're likely already in pain. Soit's kind ofagainweighing the pros and cons.

 

To close each episodewe typically share our top three takeaways from the episode. Sowe’ll start with youTravis.

 

Travis Salmon:

To mea lot of this boils down to getting as much information as you can to make the best decision that you can. I would encourage otherslike I didto researchresearchresearch. Understand the purposethe 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 providersto learn about those risksabout the benefitsthe costsother important factors. And I think also importantlyto communicate your goalsyour objectiveswith your teamto make sure that that entire team is on the same page. Communicating with your inner circlewhoever that may be — your familyyour friends — becauselike meyou will likely need them with this clinical study for a lot of reasons. And I think the third thing for methe takeaway would be: This clinical study that I participated in illustratesI thinkmy 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 forI 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 somy 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. Larkinwhat are your top three takeaways from today?

 

Dr. Paul Larkin:

I think those were greatTravis. I would say that for menumber one is just that clinical trials are the best way to advance knowledge about new treatmentsand they're really the only way to get new treatments approved. They're tremendously important and tremendously valuable. That saidI 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 trialwhether that's time or money or effort. And I think with those two in mindthe 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 keyand looking for information across a number of sourcesand knowing that there are a lot of sources out there for youincluding 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 fullestand always feel free to ask as many questionsany questionsthat come to mind when making that complex decision. SoI think that's it for me.

 

Christina Schaefer:

For memy 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 teamreally diving into what this means for you and your treatment. And your futurepotentially. And then of courseweighing 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:

ThanksChristina. ThanksDr. 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 trialsvisit arthritis.org/clinicaltrials. And for more arthritis resourcesvisit 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 notesgo to arthritis.org/podcast. Subscriberate and review us wherever you get your podcasts. If you subscribe through Spotifyleave a comment on their platformletting us know what you think about this episode. And stay in touch!