Overcoming Barriers to Clinical Trial Enrollment, with Ryan D. Nipp, MD, MPH and Electra D. Paskett, PhD, MSPH

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In today’s podcast, Dr. Ryan Nipp and Dr. Electra Paskett will discuss their article “Overcoming Barriers to Clinical Trial Enrollment,” from the 2019 ASCO Educational Book. They discuss why it is important for people with cancer to participate in clinical trials and some of the reasons people may not be able to participate in clinical trials. They also discuss finding financial resources, the informed consent process, and the role of patient navigators. Dr. Nipp is a gastrointestinal oncologist and health services researcher at Massachusetts General Hospital Cancer Center. Dr. Paskett is the Marion N. Rowley Professor of Cancer Research at The Ohio State University. She is the Director of the Division of Cancer Prevention and Control in the College of Medicine, a professor in the Division of Epidemiology in the College of Public Health, and the associate director for Population Sciences and Program Leader of the Cancer Control Program in the Comprehensive Cancer Center of OSU. She is also the director of the Center for Cancer Health Equity at the James Cancer Hospital. Published annually, the Educational Book is a collection of articles written by ASCO Annual Meeting speakers and oncology experts. Each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology. ASCO would like to thank Dr. Nipp and Dr. Paskett for discussing this topic. Dr. Ryan Nipp: My name is Ryan Nipp. I work at Massachusetts General Hospital in Boston. I am a gastrointestinal oncologist. And I do research focused on palliative care, geriatrics, health services research. And I'm a part of the Cancer Outcomes Research team at Mass General. Dr. Electra Paskett: I'm Electra Paskett. I'm at the Ohio State University. I am a Professor in the Department of Internal Medicine, College of Medicine. And I'm also the associate director for population sciences and a community engagement. And my research focuses on prevention, early detection, and working with survivors, mainly in terms of developing interventions to get people to do things to prevent cancer, detect it earlier, or live longer. And I have a specific focus in underserved and minority populations focusing on disparities. Dr. Ryan Nipp: And we are talking about a podcast where we had done some discussion at this year's ASCO meeting about overcoming barriers to clinical trial enrollment. And we were just going to go through a few questions together and kind of give our thoughts on each of these. And the first question I wanted to ask you, Dr. Paskett, is why do you think it's important for patients to be involved in cancer clinical trials? Dr. Electra Paskett: I would say for 2 reasons. First of all, we know that patients on clinical trials actually get very close monitoring, and so they would get the best of standard of care at their institutions. And secondly, the way that we progress in terms of knowing how to treat cancer, how to detect cancer early, and how to prevent cancer is through what we learn in clinical trials. Therefore, it's really important for all of us to participate in clinical trials so we can move the innovations and the new treatments and prevention strategies forward. And the only way to do that is through evidence from clinical trials. Dr. Ryan Nipp: Absolutely. I agree. Just coming at this from a clinical standpoint as a gastrointestinal oncologist, we talk about this a lot in day-to-day practice where we have the standard of care option and then we have a clinical trial option. And as you brought out, that's exactly right. At the very least, everyone should be getting the absolute best standard of care and clinical trial. From our standpoint, the way we usually discuss it is it's what we're trying to do is advance knowledge, and this is, hopefully, going to benefit the patient currently, and then also, develop new knowledge for future patients. And ultimately, this is to advance the field forward. And that's one of the things I think is so exciting about oncology. The next question we were going to talk about was what are some of the barriers that might prevent a patient from participating in a clinical trial? Dr. Electra Paskett: So I can start with a few from my perspective. We have studied this quite extensively, and we categorize the barriers into various levels. There are barriers at the patient level, barriers at the provider or the physician level, barriers at the health care system level, and then, we think, barriers even at the community or society level. And if we're talking about barriers at the patient level, a lot of times, patients don't know that there is a clinical trial available. And so that kind of affects their even ability to join a trial if they don't know that there is a trial open for them. Patients sometimes don't know a lot about clinical trials, and they're worried about clinical trials and don't quite understand what all that means. There are some myths about clinical trials using patients as guinea pigs. And that is not at all what clinical trial research is about. And so we do have to dispel some myths. And so those are some of the barriers. There's also issues related to practical things like transportation and time. Sometimes, there are more visits that are entailed. And sometimes, people don't want to get an experimental drug. They just want to get the standard of care. However, the way clinical trials are designed, you always will get at least a standard of care. So you're not getting anything worse when you're on an oncology clinical trial. If we think of barriers at the provider level, sometimes the providers don't have enough time to talk about a clinical trial to patients because it does take some time to explain and to go through the consent process. But those are some of the reasons. And even if we move up to the system level, I like to call it, is that, sometimes, we don't have protocols available for every type of cancer that we see in every patient who has cancer. So I think that's a huge barrier. And then, a lot of times, the way the trials are written are that they exclude a lot of people, meaning a lot of people can't join because they're either too old or sometimes too sick or they already had 1 type of treatment started. So those exclude a lot of people and don't let them participate in clinical trials. And then if we go up to the society or community level, there still are a lot of myths in our communities about participating in research, and we need to work hard to dispel those and make sure that all people are treated fairly in any type of research study. There's also, in some places, different policies about paying for the treatments that people receive on clinical trial. And we have to make sure that those barriers are also removed. And the last thing I want to mention is that we know that children with cancer, almost 80% of those children with cancer go on clinical trials, whereas it's anywhere from 3 to 5 percent, sometimes 8% of adults with cancer that go on clinical trial. And the question is why is that? And there's a few reasons. The first is that there are very few types of childhood cancer versus the 200 plus types of cancers adults can get. So when you have few diseases, few cancers, you can develop protocols for the few. So there are many more protocols for the few cancers that children develop. Secondly, kids with cancer are usually treated at pediatric cancer facilities, of which there are few in the United States. So again, few diseases, few places that treat kids with cancer, and they treat them the same way. And all the people who treat kids with cancer have been trained the same way to know that putting a child on a clinical trial is the best treatment. So when you have similar standards, similar training modalities, similar protocols at these fewer institutions and fewer diseases, then you can have time and have the culture we talked about at the community level and at the provider level. You have the culture that we need to put these patients on clinical trials, and it facilitates accrual. So that's sort of a few of my thoughts about that question. Dr. Ryan Nipp: Yeah. That's fantastic. I can't add a lot to that. I'll just kind of go into some of the specifics. You mentioned most of these already, like financial issues potentially representing a barrier from both the system level and from the patient perspective. When you choose to participate in a clinical trial, much like you were mentioning with the children, usually, it's a larger cancer center that offers the trial and requires travel and lodging for patients to get to the trial site. So that's also a time away from work and then just the burden of getting there and driving and paying out of pocket for those expenses. Not to mention, potentially with trials, there may be more frequent visits. So that could also add to the financial barriers. And then just the only other point I would make is going into some more detail just from the clinician perspective, as you definitely mentioned, and it's very pertinent. The time it takes for discussing a clinical trial and going through the logistics, and in a time-limited visit, that's always a burden to try to get patients with enough information that you feel like you've given them what they need to know to make an informed decision about a trial, both the risks and the benefits, and then allowing you to also feel like you've understood the trial so that you can explain it to the patient. So there's a lot of work being done on how can we equip clinicians in the clinical setting so that we can make this less of a burden on that end so that you can identify patients a little easier, too, what trials might be available for them. And then, when they are identified as a trial candidate for certain trials, so that the clinician doesn't have to memorize 20 separate trials, you know what you can do. You can bring in potential trial navigators, something we'll talk about in a few other questions, where somebody who may know all the ins and outs of that specific trial so that you can at least introduce the idea of why scientifically this might make sense, but here's the very detailed logistics of what this trial is going to look like for that patient. So just wanted to go through a few of those higher level, more detailed issues, but it was incredibly thorough description of all the potential barriers. The next question that we wanted to discuss was what are some of the resources that may be available for patients who are concerned about participating in a clinical trial for financial reasons? So we've done a lot of work on this at Mass General where, a few years back, we had looked at certain interventions where could we be identifying patients who are experiencing financial burden who may be at risk for not completing a clinical trial or not even being interested in the clinical trial just because of those financial issues that I mentioned about traveling to a trial site, having to take off from work, having to stay in a city or go to some farther place and then stay in a hotel just to be a part of the trial. We developed a program at Mass General, a financial assistance program, where people could enroll in their trial and then, once they got enrolled in the trial, if our social workers or nurses or the clinicians identified that the patient might benefit from financial assistance, they could be sent to this program, which we call the cancer care equity program. And at that time, patients would still pay for the travel and lodging, and then we had a system set up where we could reimburse them for travel and lodging. And we studied this, and we looked at our clinical trial accrual over the years before we had this program and then after the program. We have not currently done a randomized controlled trial with this program. That would be a future study that we would love to do. But when we just did this natural experiment seeing pre and post when we had this program, it did look like we saw an increasing clinical trial accrual at our institution during those years after the program was instituted. But obviously, without a randomized trial, there's many reasons that could contribute to that. We also then, later on, gave patients surveys over time while they were participating in a clinical trial asking them about their financial burden over time just to see how are these patients' financial burden evolving over time on a trial, because you worry about when someone signs up for a trial, at that moment, they're willing to do anything just to get the appropriate best possible treatment. And then what happens with their finances from that point forward, you might not be thinking about from the beginning. So we surveyed a group of people who were enrolled in our program with financial assistance, and then we surveyed a group of control or usual care patients who were not getting the assistance but who were also on a clinical trial. Again, not a randomized trial for this, but we did see a trend where the group who was in the program had steady to improved levels of financial burden, whereas the group that was not getting the financial assistance, their financial burdens appeared to get worse over time. So that was some more evidence that having these financial assistance programs may help. And this is a growing idea in the community, but there's a lot more research that needs to be done there. Some other evidence or some other things that we can be doing, at least at the clinical level or for patients when they come to a clinic right now, that where we don't have studies like that open, I would argue that, at the very least, it would be helpful for patients to know kind of what's required of the trial, how often are the trial visits going to take place, what's going to be entailed in those visits, how long are those daily visits when they do come to the clinic for their trial visit, how long are they going to be there, things like that just so you can plan ahead and kind of know how much of an effort is this going to take. And then there's also resources at many community or many cancer centers where you can have social workers or community resources available to talk with patients about what other resources might be available to help with either financial assistance or just knowing what the expenses may be related to the supportive care medications, related to the trial, related to the labs and things like that just so that taking a little bit of the uncertainty out of the picture so that people have an idea of what may be to come and being able to plan ahead. Dr. Electra Paskett: Those are really great suggestions. And we have a very small grant from a foundation to provide up to $250 financial assistance for any cancer patient. And they have to qualify. There are income guidelines that qualify them. And we are just inundated with requests from our cancer patients. And this is irrespective of a clinical trial, but a lot of our patients are on clinical trials. And we can give them up to $250 each year. And the things that we might think are a little bit to help with gas or food or to get out of the parking lot are huge things to our patients. And I think that, sometimes, we don't fully appreciate the issues that our patients face when they come here to receive care. And I think being very astute and aware of that and trying proactively to, A, identify them. And we do that with our patient navigators. And it's actually a financial navigator that we have now that administers this money. And so being aware, asking about it, because it will make people, A, adherent, but B, just really one little thing from the stress that they're dealing with in being diagnosed and treated with cancer. Dr. Ryan Nipp: Absolutely agree. The next question for us to discuss is what do we think is important for patients to know about the informed consent process? Dr. Electra Paskett: Okay. So it is a process. That was your last word. Process. And a lot of times, we forget that it's a process. And we researchers sometimes just think about the informed consent document, but it's really a process. And the informed consent document or the consent form is a part of it. And it is a big part of it, but people need to be informed about the research. And I think it's very important when we, first of all, craft our consent forms, that they need to be in English, not in medical terms. They have to be in a good reading level, 5th to 8th grade if possible, and we should inform the patient by going through the subheadings on the consent form. And somebody needs to walk the patient through the subheadings on the consent form. A lot of consent forms, especially for treatment trials, have pictures to show the different treatments. And we definitely need to walk patients through the consent form, let them ask questions. If they want to take the consent form and talk to their family about it, we need to let them do that. But it really is an informed consent process, and we have to let that process occur. Dr. Ryan Nipp: Agree, 100%. The other issue I think about in clinic when we're doing this is, often, we're doing informed consent, at least as oncologists, when we do routine chemotherapy. And when you're doing a routine chemotherapy consent, you're usually talking about the potential risks and benefits. And with most routine chemotherapy, they've been through trials already, so we have an idea of what those potential risks and benefits could be. Something I should have mentioned earlier, one of the things that I think is interesting related to the barriers, like Dr. Paskett was mentioning, where if the patients that we enroll on trials are younger and healthier than real life, then you do have a little bit of variation as far as when you see a patient in clinic, they may look a little different than what the clinical trial population looked like. So that gives a little bit of a gray zone of do we absolutely know what the risks and benefits are? But then, when it comes to a clinical trial informed consent process, that's where I think there's some interesting ethical dilemma that you're in some ways that we run into where you would love to give people the potential risks and know exactly what to expect, and you'd love to be able to give the potential benefits, but that's somewhat the essence of a clinical trial where we don't quite yet know what the benefits will be. We hope that there's going to be benefits. That's why we design the trial the way we do. And so you can kind of go through those potential benefits, but you also don't want to overplay it and give false hope. And then, on the other hand, when you're talking about the risks, you want to be realistic and say that this is a treatment, and based on the mechanism, it could cause these risks, but we're not 100% sure. That's partly what we're going to be studying with the studies. So I find that an interesting part of the informed consent process when you're talking about a clinical trial where you're gaining new knowledge, and that's part of what you will be gaining are the risks and the benefits that you can inform future patients when this is no longer on a study and is part of routine care. Dr. Electra Paskett: Yep. Those are great points. And it's not meant to scare people, but it really does. People need to be informed. Dr. Ryan Nipp: And then the last question for us was how can patient navigators help patients overcome some of the barriers to enrolling in cancer clinical trials? Dr. Electra Paskett: So we've done a lot of work in patient navigation. And we use navigators now in many of our clinics. I talked about our financial navigators. But our navigators are people who are our laypeople, and they, a lot of times, come from the same background as the patients. And so they're able to gain trust of the patients and explain treatments in clinical trials and the things on the consent forms we've just been talking about to patients in a language that, sometimes, we as medical professionals don't use. And so navigators can help with that. And the job of navigator is to identify and then address the individual barriers that a patient has to completing their recommended treatment given them by their health care provider. And that's what navigators do. They can assess what the individual barriers are. And sometimes, they might be things like transportation. They might be childcare or eldercare or things like that. And the navigators have the resources and the connections in the institution and out in the community to address the individual barriers that a patient has. And every patient has different barriers. And so doing this intake assessment allows the navigators to identify and then tailor their strategies to each individual. Dr. Ryan Nipp: Yeah. And then just to add on what I've kind of been learning from you, Dr. Paskett, is financial navigators are, essentially, there to make the entire process more streamlined and smooth for the patient as well as, potentially, the clinician as we're going through this process. It's always nice. One thing I find that's helpful about a lot of the clinical trials when we have patients on them is that what comes along with a lot of clinical trials is that you also have the resources that come along with the trial, which are the research assistants or the research nurses who are helping schedule things and keeping things organized. And that's one of the things that I could see as a clinical trial navigator to have just another set of resources, another set of eyes paying attention to the details, which can only help. It's one of these amazing potential interventions where it's almost all we're doing is trying to help. And so one of the points I wanted to make is I think we need a lot more research in this area. And I think it's ripe for research, but it's also one of those things where it's a little complicated, a lot like when we had done the financial assistance program where you think almost anyone could benefit, so then you have this difficulty with randomizing because everyone, you would hope, would have access to this, but that's currently not the standard, and that's why I think we need to prove it with more research. Dr. Electra Paskett: Right. I agree. And one of the things when we first started offering navigation was our providers said, "Oh. I don't have to do that [laughter]." And so that they can spend more time working on the medical aspects versus these other aspects that the navigators are very competent to address. Dr. Ryan Nipp: Absolutely. Well, I think that's all the questions that we were expected to address. Any final thoughts, Dr. Paskett? Dr. Electra Paskett: No. Thank you. This has been fun. Been fun working with you and ASCO and the meeting and this. It's great. Dr. Ryan Nipp: Agree. Again, it's always a joy working with ASCO [laughter]. Thank you. Thank you, everybody. ASCO: Thank you Dr. Nipp and Dr. Paskett. Please visit ASCO.org/edbook to read the full article. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.