John Kingrey, MD:
My name is John Kingrey. I’m the director of the Pulmonary Hypertension Center at INTEGRIS Health. I’m a pulmonologist in pulmonary hypertension in Oklahoma City. I’ve been involved in pulmonary hypertension starting in the early part of my medical training, and I chose to pursue pulmonary hypertension as a subspecialty within pulmonary medicine and have been doing that ever since.
Nicole Fitzgerald:
My name is Nicole Fitzgerald. I am 44 years old and I am a pulmonary hypertension patient. I’m originally from Los Angeles, but I currently live in Oklahoma City, where I have lived for the past six years.
John Kingrey, MD:
Today, we’re going to discuss the importance of the physician-patient relationship as it relates to participation in clinical trials. Clinical trials are an essential part of most fields of medicine, but particularly pulmonary hypertension at this time, because there is so much development of new pathways and new agents that can potentially change the landscape of the disease.
At our pulmonary hypertension center, we have typically multiple clinical trials going on at one time. The nature of each clinical trial is a little bit different, and the population that we are investigating is also different, but it’s all centered around patients with pulmonary hypertension. However, it’s really important to understand that clinical trials have a very focused population for which they’re interested in, because they’re trying to investigate whether or not a certain product or a certain device could be effective in this specific disease state that they think that it will work in.
Each patient that comes in, in some way, either formally or informally is considered for clinical trials. We know as a center, what our current clinical trial profile looks like and the specific population that could be potential candidates. When I’m in a clinic visit with a patient, I am thinking about what we have potentially to offer them and whether or not they would be a candidate. For a lot of our patients, I know that because of either how long they’ve had the disease or the specific nature of their disease and its severity, they may not be a clinical trial candidate, so it’s not really brought up in many patient encounters.
However, when I have a patient that I think may fit one of our clinical trials and I think, more importantly, that it would be a good opportunity that would be of benefit to the patient, then that’s when I will bring that up, usually as part of a typical clinic encounter. Sometimes, depending on the clinical trial, we will have a special visit to discuss a clinical trial opportunity with myself or my partner, to see if the patient would be interested and if they would be a good fit.
Nicole Fitzgerald:
Because I was diagnosed so quickly before my husband and I had to make a big cross-country move, pulmonary hypertension was something obviously I had never heard of. It just was not even on my radar as something I should even know that this is something that could happen. I just had no idea that it even existed. I would say because we moved so soon after and I was consumed with trying to just find my footing in terms of the move, and then finding the right doctors in Oklahoma, because I had none when I came out here, there was a lot that I was learning to navigate. Obviously, it was a lot of change at once. For a long time, just trying to get myself with the right doctors, having all the right testing done, kind of getting a control on my medicines and what things I should take. Just getting myself stable took a very long time.
The first year or so I would say was the most challenging, just because of all the newness and all the adjustments that were being made in my life in general, so it took a lot. I got worse before I got better. So, like I said, just getting stable I would say was my biggest priority for a very long time. It took a while before I started to hear from other patients that there were clinical trials available. Once those opportunities became available to me, that was something that I was very interested in, because I wanted to kind of be as aggressive as possible with treating my PH.
Initially, that was not even on my radar. It was just more about getting myself to a point in my health where I was stable and can do normal things, which was a real big challenge for me, especially early on. So, it was primarily online through Facebook support groups for patients with PH. You kind of hear rumblings, just word of mouth of other patients were taking a particular trial, or participating here or there. Questions had been brought up with their physicians wherever they were from.
You kind of branch out a little bit to know that there are trials taking place. It wasn’t something where I right away sought that out for myself. For me as a patient, I was just excited that research was being done. I think that’s something that all of us as patients just want to know, that there’s hope out there. I think we get kind of so bogged down in the drugs that we have available to us. There’s only so many and you are put on one thing, and you either respond to it well or you don’t, and then they take you off, and maybe you get put on something else depending on how you’re feeling.
So, after a while you just kind of get kind of in that routine, but you want to know that there is hope coming, that there are better drugs coming, that there’s something else out there. So, I think as patients, we’re just all really excited and curious to know that there’s research being done, there’s trials being done. So, that was something exciting that I had heard about online, but it wasn’t anything necessarily specific where I right away brought that up to Dr. Kingrey. That was something that he brought up with me and I’m so happy he did. It worked out well for me in the end.
John Kingrey, MD:
I think that one thing that’s really important for patients to understand, is that clinical trial work is really, really hard work. The ability to recruit patients for clinical trial takes a lot of effort in identifying the right patient population and identifying patients who are not excluded for a number of many reasons that patients can excluded from trials, and again that they have the right disease state.
The next step is finding someone who is willing and open to the concept of a clinical trial. I think that there are a lot of people out there that look at clinical trials as a big risk. A phrase that I hear a lot and I know that other providers hear a lot is, patients say, “Well, am I going to be a Guinea pig?” That is kind of an antiquated way of looking at things, because the clinical trial space is so heavily regulated and protected, even in the hands of a provider who may not be paying it that close of attention to detail. It’s really, really hard to enroll a patient in a clinical trial and have them be subject to a real significant risk, that at least has not been properly spelled out.
Many people don’t understand, for example, that when it gets to a phase of clinical trial where human beings are involved, that the medications or the devices, or whatever it might be have been trialed in both animal studies and also in healthy patients that don’t have the disease, just to demonstrate safety. That’s a barrier for some people. I think though, that probably the biggest barrier is the relationship that they have with their physician, because it doesn’t matter if I told a patient that I’ve got a clinical trial in Tylenol that’s been on the market for decades. If they don’t trust me and they don’t have a relationship with me, it’s unlikely that that person’s going to want to be part of a clinical trial.
There’s two reasons generally that people end up doing a clinical trial. One is that they look at the potential benefit for their own health, which of course is a huge reason that it exists. The other is because that patient really wants to benefit others who may come after them, who will be suffering from a similar disease and now potentially have a new therapy, because of the way that was laid forward by clinical trial participants.
The most important thing that I would say to patients and also to physicians, is if you want to be involved in a clinical trial, and from my standpoint, if you want your patients to be involved, you better know your patients. You better know more than just what’s in black and white. You better have a relationship with them. And if you don’t, it’s going to be really, really hard to bring up a clinical trial that’s going to potentially come across as very scary and very experimental, when in reality there’s a lot of protection built into clinical trials, particularly in the United States, that is squarely focused on protecting the patient.
Another element in considering clinical trial participation is making sure that the clinical trial is going to fit within the signature that the patient needs. Another way of saying that is, consideration of participation in clinical trials is really important to tailor the needs of the patient and ensure that the clinical trial fits within the boundaries of what would be an individualized treatment plan. In pulmonary hypertension, for example, we do have some guidelines regarding treatment and how patients should generally be approached. However, it is not cookie cutter. There are several different pathways that patients can go down and arrive at a good outcome, but the considerations of how to get there are variable. They would include patient’s preferences on how they take medicines, patient’s tolerance of certain side effects that certain classes of medications have, the amount of pills that someone needs to take and so forth.
So in clinical trial, the point here is, every patient has a very individualized treatment plan, and when we think about what the next thing is that the patient needs, we have to ask ourselves, does any of the clinical trials that I’m offering, assuming that the patient fits the general profile, is that going to be beneficial to them?
So, severity of disease is interesting, because some clinical trials exclude patients who are doing too well, others exclude patients who are too sick. You have to be able to take that into account, as to whether or not the medication or the certain application of a medication is handled. We have to be incredibly prescriptive in identifying the right type of patient for the right clinical trial.
Another element of this is helping the patient understand where the potential treatment comes into play. Many times, I will have a patient, for example, that comes to me and is doing worse. If I have a clinical trial that that patient would fit, but that particular clinical trial has a study design that is very common, where neither myself nor the patient know if they’re going to get the medication, meaning that it’s placebo-blinded, so it’s a double-blinded placebo trial, and I know that that patient needs more therapy, I don’t feel like it would be ethical. If I have something else to use that I know would help them that would be already on the market, then I’m not going to have that patient be in a clinical trial, where they could be going six or 12 months without getting anything. Or even if they did get the medicine, something that’s clearly under investigation, when I could be reaching into the cupboard and grabbing a medicine that is already available that I know would be immediately beneficial.
There are a lot of considerations. That’s just one example. Other things would include patients access to coming to a clinical trial. In Oklahoma City, we have many patients who live hours away from us, and though clinical trials are incredibly good about making sure that the patient doesn’t have out-of-pocket costs for things like travel, it still can be a matter of time not available or reasonable for the patient to do it, because of travel time or perhaps they work and they wouldn’t be able to get off work. So there’s lots of things that have to be under consideration before somebody really is able to fit in a clinical trial.
Nicole Fitzgerald:
For me, I think a lot of consideration, obviously, was given to my health at the time. During that period, I was a little bit more stable, but not as good as I had been or as I could be. So, it was one of those things where I just kind of fit into a category where it was like, okay, well, I’m not super sick. I’m not as sick as I was initially when I was diagnosed and at various times had been, but I’m also not feeling great. I’m not feeling at my very best. I’m sure I could be doing better. So, it was one of those things where it was like, okay, well, I’m just kind of at a standstill, but not at a place where I am necessarily as good as I want to be. For me, it was obviously interesting to have something that could help me more than I was being helped already.
Then, there’s also, as Dr. Kingrey mentioned earlier, you’re in a position where you want to help yourself, but then there’s also that feeling of, okay, well I can do something potentially that can help a lot of other patients. So for me, that’s obviously always a factor. There’s a lot of things that get taken into consideration when you want to participate in a trial. Obviously, you have to meet the criteria of whatever trial you’re participating in.
There’s things that involve just your own personal lifestyle, the way that you might administer the medication, how often the trial visits are, Like he mentioned, Oklahoma City, there’s people that live pretty far out. I am fortunate that I live only 20 minutes away from the center where all my trial visits are, so it’s convenient for me, as opposed to other people might have a lot more difficulty just getting back and forth. There are lots of things that factor in, but for me it seemed like it would be a good fit and the time constraints weren’t anything extraordinary. So, it just worked out where I felt like, okay, this is something that could really benefit me, but also potentially help others down the road.
John Kingrey, MD:
Once a patient is identified as a potential candidate for a clinical trial, that’s just the beginning. Usually the next step is, I will have a conversation with the patient about the opportunity to participate in a clinical trial. With that, will be a general overview of the type of patient that the clinical trial is looking for, which obviously the patient you’re talking to should fit that. Then, I will give an overview of what the general purpose of the trial is and how it’s constructed, in very high level terms, not getting into the nitty-gritty at that point, but just to explain generally what we’re doing.
The next thing that I do is if the patient has interest, then, I will talk to my clinical trial coordinator and they will give the patient a phone call. Or, if the coordinator is available, I’ll have them come down to the clinic right there in real time, if both the coordinator and the patient has the time. Either way, there’s a conversation that takes place between the clinical trial coordinator and the patient that involves additional detail to kind of put a little bit more meat on the bones, so to speak. At that point, the patient says, “Yes, I’m really interested in this.”
Then, typically the clinical trial coordinator will go through exclusion and inclusion criteria to make sure that the patient is the right fit. Sometimes that happens independently. Sometimes the clinical trial coordinator will have questions, and they will come to me and we’ll make sure that yes, the patient is the right fit. Once we’ve cleared that step and there isn’t anything obvious, then, starts the process of an official screening. Screening is when the patient comes in and provides consent to participate in the clinical trial. Then, a series of tests and questions happen to make sure that there isn’t anything else right before the patient would go into the clinical trial that would potentially exclude them.
The cool thing is, is that patients with pulmonary hypertension are not going to be unfamiliar with most of what is required. Every trial is different, but most trials are going to have some combination of requiring a six-minute walk, lung function tests, imaging, sometimes a CT scan, sometimes perhaps an MRI, chest x-ray. Some clinical trials will require a repeat heart catheterization within a certain period of time of enrolling in the clinical trial. Not all of them. Some of them just want to demonstrate that at some point, yes, the patient was properly diagnosed with pulmonary hypertension of whatever variety the study is looking at. Always blood work and then a questionnaire. Now, that is not necessarily a comprehensive list. There could be a few other things, but it’s pretty rare that there’s something that the patient has never heard of before that needs to be done as part of a clinical trial evaluation for pulmonary hypertension, because most of what we’re looking at are things that we’re already doing in the evaluation of a patient.
Once you go through all of that, it’s kind of like a final system of checks and balances. Okay, we did the screening testing, everything seems to be checked out, and yep, you are a go. Everything is good. There’s nothing that has excluded you. You’re exactly the right patient. Once you clear that hurdle, then the patient becomes enrolled officially in the clinical trial. Of course, at that point, it depends on how the trial is designed. There could be a medication involved or perhaps a different application of a known medication, perhaps a device or something that the patient will need to have with them, or inserted or whatever. There’s lots of different possibilities, but that process of screening really starts well before an official screening. Then, you go through the testing to make sure that everything still checks out.
Then, you go through the clinical trial. Clinical trials are of various duration. Usually in pulmonary hypertension, it’s a pretty common interval is usually at least six months. There have been certainly clinical trials that have lasted shorter than that. There are some that go beyond that. Obviously, the patient is going to know that before they would ever even sign consent, what the duration of the trial is. So, you go through the clinical trial.
At the end of the investigation period, many clinical trials then have an opportunity to go into what’s called an open label extension. If it’s a drug trial and the drug is not approved on the market yet, then the only way to get access to the medication is within the confines of a clinical trial. So the cool thing is, and it’s really kind of a fringe benefit of participating in the clinical trial, is the patient many times, and the patient would know this before entering the trial if this were an option, it’s not held out as a mystery until you get done with the trial period. So let’s say the trial is six months. At the end of the six months, you and the physician are unaware if you’ve got the drug, if it was a drug trial, for example. At the end of the six months, many clinical trials are structured so that you can enter into an open label extension, which means the patient is guaranteed to get the drug, not a placebo, but the actual drug, for a period of time that could go on for even years.
Again, that’s something that is spelled out in advance, because even at the end of a clinical trial, it’s not like, oh, you enroll all the people and then a few days later you go to the Food and Drug Administration and they say, “Okay, good job. We’ll let it go,” and you can put the drug on the market. It’s much more complicated than that, and time is measured in years on these sorts of things before the drug may potentially be available to the public.
Nicole, in the clinical trial that she participated in, she’s still getting a medication that is not available to anybody in the public. A doctor can’t go and just prescribe this medication, and she could very well be on it for several years before the medication is ultimately approved by the Food and Drug Administration. Or, if the trial showed that there was not benefit to it, then she would go off it at that point too.
Nicole Fitzgerald:
I knew going in if for some reason I was not responding well to the drug or if it just didn’t fit in time-wise for any reason at all that I wanted to leave, that I was able to do so. That was something that was made very clear from the beginning. I really just want to stress, I know that there’s a lot of apprehension from some patients, that maybe they feel like they are going to be a Guinea pig in participating, or maybe they don’t have a lot of trust within their doctor-patient relationship, or they might’ve heard anecdotal stories about someone that had a bad experience in a trial. I have felt nothing but respect from the people that ran the clinical trial that I am participating in. Every single person has been very respectful of me, of my time, of my participation. They have really gone out of their way to make sure that appointments run as smoothly as possible, as efficiently as possible, so that my time and their time isn’t wasted. And just that all around, I have a good experience.
I have been really, really fortunate in that respect, and I think that that is more common than the other experience, which is obviously anecdotal that people have heard, that is not a good experience and they feel like they’re doing this and not really getting anywhere, or not hearing anything and maybe feeling somehow exploited. That is not at all what I have experienced.
When I was first looking for clinical trials, I had to do some legwork of my own. I had heard about certain trials that were out there and I went online. I went to www.clinicaltrials.gov. I looked around to see what would be available for me, if there was anything in my area that I could participate in.
It turns out that the trial I had initially been looking into and was hopeful I could participate in, that wasn’t available to me, but I ended up in another trial instead. I was a participant in the TORREY study, and that worked out really well for me. I also just want to say one of the great benefits obviously, aside from having early access to a drug that may get approved down the road is, all the testing that is required is all covered by the trial. So, all of the blood work that I have done and the extra tests that are involved, including right heart cath, all of that that I have had done is all paid for by the trial. So, I kind of feel lucky that I’ve had all of this extra testing that hasn’t been charged to my insurance. I’m appreciative of that, so that’s an added benefit as well.
John Kingrey, MD:
Clinical trial work is really, really exciting. It’s exciting for the patient, because it’s an opportunity to have exposure to frontier medicine, meaning the latest and greatest of what’s out there. It’s giving a patient access to care and access to therapies that they wouldn’t have in any other way. That’s probably the single greatest element of doing clinical trial. As a physician, it’s really exciting, because we get to be part of that and to learn, along with the patients, about the new therapies that are being investigated. Along this path, I can tell you that some of the unanticipated things that happen is, from a physician perspective, is you get to know your patient a lot better. You’re seeing them more frequently, you get to talk to them more frequently. You are asking of course about things that are relevant to not only the clinical trial, but the other symptoms or problems they may be having. So, you get a lot more face time with your patients and the patients get more face time with you, which I think is mutually beneficial.
The other thing is, is that I think patients realize when they participate in clinical trials, I can only talk about pulmonary hypertension, because I haven’t been knee-deep in clinical trials in any other disease state. But the pulmonary hypertension community is so tight and so committed to helping patients, that the patients really get to catch the spirit of not only what’s going on in their own body, but what’s going on in the entire pulmonary hypertension community globally, what’s happening to try to move the disease forward.
That’s really exciting. I think that’s really exciting for patients to be able to be a part of that, because you’re literally creating history. You are laying the groundwork for generations to come. Even if the drug doesn’t work or whatever’s being investigated doesn’t work, that’s really helpful information. Patients are like, “Well, what if this doesn’t turn out?” Well, you know what? That’s also beneficial, because generally in medicine, you have to have a lot more failures before you nail the successes, and that’s certainly the case in pulmonary hypertension, something that we see. Of course, we hope that that’s not the case. The only way to find out is through the clinical trial space.
I also think that patients understand that the sponsors of the trials are so committed to helping these patients get access to care. The other thing is, is that I think my patients feel it from the sponsor and from the people who are administering the clinical trials, that these people actually really care, and they’re really invested in trying to make things better. I think what that does is that takes you beyond from just being a patient and you really catch the spirit of what pulmonary hypertension is really all about. I’d like to thank you all for listening. My name is Dr. John Kingrey.
Nicole Fitzgerald:
And I’m Nicole Fitzgerald, and I’m aware that I’m rare.