RARE Daily

Addressing the Barriers to Patient Participation in Clinical Trials

March 23, 2023

A significant obstacle to getting patients to participate in rare disease clinical trials, particularly children, is the burden placed on patients and their families to address the logistical challenges of arranging travel, fronting expenses, and completing paperwork for reimbursement. In fact, nearly two-third of patients and caregivers say travel stopped them from participating in a clinical trial. Clincierge seeks to remove the burden of participation in clinical trials on patients and caregivers by managing the logistics of travel and reimbursement, as well as assigning coordinators to them during the life of a study. We spoke to Scott Gray, co-founder and CEO of Clincierge, about the burdens placed on patients who want to participate in a clinical trial, how Clincierge works to eliminate those, and the impact its work has on recruitment and retention of patients in clinical studies.


Daniel Levine: Scott, thanks for joining us,

Scott Gray: Danny. A pleasure to be with you.

Daniel Levine: We’re going to talk about pediatric rare disease trials, Clincierge, and how it seeks to address barriers to participation and enhance retention through its services. Let’s start with the problems you’re trying to address. What are the challenges trial sponsors face with enrollment and retention in rare disease patients, particularly pediatric patients, in clinical trials?

Scott Gray: Well, you know, the challenges have always been [there] even across all sorts of clinical trials, whether they be rare disease or pediatric rare disease. Recruitment and retention are the two most pressing issues for trial sponsors and the CROs. From the statistics that we look at, only about 6 percent of clinical trials finish on time. Eighty percent are delayed by at least one month or more. And this relates to the ability to recruit and retain patients. With the current estimate of about 30 percent of patients dropping out, there are several reasons why recruitment and retention continue to be significant issues in the clinical trial space. First of all, with the rare disease population, it’s very small to begin with. And often sponsors may be working, multiple sponsors may be working on a solution—a  genetic treatment or a product or drug at the same time—and they’re trying to pull from the same small population of rare disease patients. So, there’s competition involved even in just getting those that they want in the trial involved. So, by adding beneficial services that support, it helps get them in. There are other challenges, such as with pediatric trials. Not only the patient, but the entire family may have to travel or temporary relocate. So, you can understand the logistics challenges, the family challenges that may be involved, which ties into financial insecurity, loss of wages, unemployment, et cetera. The cost of purchasing services, hotel accommodations, to go to a different location for the trial. Some of the patients themselves have mobility issues. They may be too sick or weak for the regimen of travel that may be required. And then there’s the whole emotional aspect. What is the anxiety and stress surrounding trial logistics, even beyond the thought of my child is in a clinical trial that may or may not benefit what his or her condition is. So, that touches on a lot of the challenges that we see in the rare disease pediatric patient trials.

Daniel Levine: This has a bottom line effect for trial sponsors. Is there any way to quantify what this does to the cost of conducting a study, particularly in rare disease?

Scott Gray: Well, in rare disease, we’ve looked out at some of the data. There was a white paper published several years ago that spoke to the revenue lost by a company that brings a rare disease treatment to market. And what they cited was a loss of about $6,500 per day. I’m sorry. The loss of revenue is about $600,000 per day for rare disease. And if we think about the whole big drug population and blockbuster drugs, that’s $8 million a day. We know we want these companies to generate revenue because it’s how they fund additional research to bring other treatments to market. And thinking about the whole area of clinical trials, a clinical trial—and many people don’t know what the investment is—trial cost could range from $44 million to over $115 million. So you can see why they want to recruit, retain, and get their outcomes data as fast as possible so that they have the potential of submitting the outcomes data and coming to market. And the real mission of this is to benefit others. That’s what we want to get done. We want to have the trials conclude effectively as quickly as possible so others may benefit from this research that’s been done.

Daniel Levine: Clincierge did a patient voice survey to understand patient and caregiver experiences in clinical trials. You had mentioned earlier the emotional component of this, but there is a lot of emotion for patients that come with participation in a study. And it’s not just excitement, which many of them feel about being in a study, but they also express a lot of stress. What did you find?

Scott Gray: Well, thank you, that’s a good question. We launched the Voice of the Patients project because we wanted to better understand, beyond the science, what are people experiencing as they think about participation in a clinical trial or having a family member, especially a pediatric family member, participate in a clinical trial. So, we looked at it from different aspects such as before they enroll, what goes on during their treatment phases, and then throughout their study completion. We wanted to learn more about their emotions in order to effectively develop patient support strategies that continue to reduce the barriers, increase retention, improve outcomes in rare disease clinical trials. And what we found is that the majority of patients, and statistically that was at 87 percent, said that participating in a trial was stressful for themselves in their family. Eighty three of the patients reported feeling excitement related to participation, but also reported feelings of anxiety, uncertainty, the overall exhaustion from having to navigate the entire process on their own. And among all the barriers that patients face when entering a trial, travel was one of the primary reasons [for] deciding not to participate in one or more clinical trials that they had been approached to participate in. Sixty eight percent of the patients we surveyed said that traveling to the site was difficult because of reasons such as having to figure out how to coordinate their own travel arrangements, the flights, rail, travel, ground, transportation, scheduling, hotel stays, and think about what goes on in your daily life, missing work, or children having to miss school—significant challenges. So, that’s what we learned about the patients that we were wanting to build our services toward.

Daniel Levine: Are patients generally left to fend for themselves in handling all the logistics of this?

Scott Gray: That has been the traditional method, Danny. Yes. When we created the service, when a client of ours asked if we could help them navigate the patients to the rare disease sites coming from 18 countries outside the U.S. to the few sites that were enabled to do the research, and coming from where we were in corporate meetings and events management, which is just the same thing, logistics of moving people around the world, meeting delegates, you know, setting up our services so that they have a great experience when they get to this conference. We applied the same philosophies and as we researched this clinical trial space [it] was like, okay, so we’ve now defined or found another example of the definition of insanity, where we do it over and over the same way and expect a different outcome. We do it over and over the same way we expect retention to increase. We do it over and over the same way we expect recruitment to be easier. That’s not the case. So, by adding these services the patients no longer have to fend for themselves. They’re given support outside of what they have to endure inside the clinical trial, the medical aspects themselves.

Daniel Levine: And given that we’re dealing with pediatric clinical trials, you mentioned the stress on the family, but what generally happens? Do whole families come for a clinical study and how extended or disruptive is that?

Scott Gray: Yeah, you’re right. Pediatric trials are notoriously challenging with the unique barriers because these patients are under 18 years old, many are infants, so participation does affect the entire family. We’ve already mentioned the scheduling complex as well, and think about families with multiple children. How exceptionally busy are they between schoolwork, sports, or other extracurricular activities? The parent of the child may have to wear many different hats, including being the chauffeur, an advocate perhaps administering medication, a researcher, nutritionist, pharmacist, teacher. So, the stress associated with keeping all the balls in the air, so to speak, can be physically and emotionally exhausting. And there’s also another aspect, sometimes with these rare genetic disorders, it’s affecting more than one child in the family. So, you’ve just amplified the amount of activity and the amount of concern and anxiety that goes into a patient or the family being enrolled. And in many instances, because of rare disease and the few sites that are enabled to do the study, we are relocating entire families for the duration of the trial regimen so that the pediatric patient can participate. And then we have services to what we call repatriate them back to their city, their state, their country.

Daniel Levine: Patients aren’t compensated for their participation in a clinical trial, but they do get reimbursed for certain expenses. What do sponsors cover for participants and their families?

Scott Gray: Well on that, there are some trials where patients do get paid like some of the big vaccine trials that have happened recently. There may be a $25 stipend for going and getting the vaccination to encourage participation. But typically, in some of these rare diseases, especially when we’re working with small biotechs with limited budgets, they may not have the budget or they haven’t thought about what the value is on investing in these support services. Now that we’re in this space and providing patient support, what we do provide is booking air and ground transportation, document translations, in-person interpreters may be required, visa requirements if we are transporting a family or relocating a family across borders, navigating all the special travel accommodations, wheelchair accessible vehicles, and making sure that the hotel room is compliant with whatever their mobility needs may be. Yes, those are the things that we look at and this is what the sponsors are now providing the funds for to do so that we can make the purchases on behalf of the patients, reduce the financial burden as much as possible with still the potential for incidental reimbursement allowed for, you know, meals or bottles of water in the airport—incidental such as that.

Daniel Levine: I know people think about things like work disruption as far as the financial impact of participating in these studies, but do they have to front their travel expenses generally and when they participate in a study?

Scott Gray: That has been the normal way of it being done. They would in the past. In the years before we launched Clincierge, the typical method was that the sponsor or the CRO—the trial management organization—they might identify a travel agency where the patients can call into to book their travel, but they were still required to provide their own credit card, then submit the receipts and await reimbursement, which, from what we’ve learned, often took more than a month or so. And if we’re thinking about wanting to level the socioeconomic playing field of who can participate in a clinical trial and of course to increase the diversity of patients who are in clinical trials, we need to eliminate any financial burdens. So, you’re right, they did have to pay for it on their own and then await reimbursement. But if we think about it, many people can’t even afford to buy several hundreds of dollars’ worth, or thousands of dollars’ worth of air tickets and hotel room stays and then wait for eight to 12 weeks for reimbursement.

Daniel Levine: There’s been a lot of interest and growing use of decentralized clinical trials using communications and monitoring technologies, in essence, to bring the trial to the patient. I think this is an acknowledgement of the burdens that clinical trials can have on patient participation. To what extent has this solved the problem?

Scott Gray: So, decentralized clinical trials or DCTs—we the abbreviation—they absolutely have a place in the clinical trial ecosphere, you know, leveraging wearable medical devices, the telemedicine opportunities, in-home visits instead of the patients going out, local healthcare providers and laboratories in place of visits of the traditional study sites. So, they have these solutions, have many potential benefits, such as better data quality, more convenient experience for the patient, and in many cases, they assist in shortening the time it takes to get new drugs to market. However, the same technology enabled enabling DCTs to succeed can also contribute to their downfall. Wearables and monitoring devices, for example, require patients to have access to reliable internet connectivity and the ability or desire to learn to use them as intended. Virtual participation may not be an option for patients unfamiliar with technology or those living in rural or poverty stricken areas. I think even the Alzheimer’s studies that we support where there may be some potential for monitoring of cognition, et cetera, many of these patients are not comfortable with technology that when we interact with them, we are doing it via telephone. And further, trials for patients, where the rare diseases are often too complicated for decentralization or a decentralized clinical trial approach, the self-reporting, at-home visits are not always feasible for these patients and their caregivers. And for these patients, many of them prefer the reassurance of meeting with specialized staff to address the complexity of their medical concerns. So, the DCT trials are not necessarily designed to offer the high-touch support that these patients and their caregivers often require.

Daniel Levine: Well, take a step back. How did Clincierge come about?

Scott Gray: I mentioned earlier that we were initially corporate meetings and events management, primarily pharmaceutical customers, so with this deep hospitality mentality. And it was a biotech customer for whom we were organizing their investigator meetings for a rare disease clinical trial in the U.S. They’re the one who asked if we could help create a service when they got the funding and approval to launch in 18 countries, ex-U.S. for this rare disease trial where the patient regimen was to travel to the site for a three day visit every 21 days for 18 months. And the site’s, again, not proximal to where the patients resided, so thus was born the Clincierge service. And we tapped some of our hospitality colleagues at that time who were around the globe that we thought that alignment of the Clincierge coordinators who had the front line communication with the patients and the sites. The Clincierge coordinator is planning the logistics for the patient or the families for each of the site visits. And because we place them culturally, linguistically, time zone aligned, there’s an immediate trust that gets built between the patients, the site, and our Clincierge coordinators in managing what has to happen for them or for their family member to participate in the trial. They build this trust, the coordinator is there to help them if travel logistics go awry, if weather impedes flights, if whatever needs to be reorganized, the coordinator is there to help them through it so that they can focus on the trial regimen itself and doing as much as they can to feel better.

Daniel Levine: And how does the company typically work with trial sponsors? At what point do you get involved and what’s the scope of your responsibilities?

Scott Gray: The ideal is that we are considered at the point where the protocol is being designed, that we are identified as one of the vendors who will be supporting the patients. You know, think about the sites that are being brought on board. Think about perhaps there’s a CRO involved in managing the trial. And then Clincierge itself, in most cases, we are contracted directly with the sponsors and then they provide the funds for us to support the patient’s logistics.

Daniel Levine: How do you work with study participants? It sounds very high touch.

Scott Gray: It is. Therein lies the “cierge” part of the Clincierge in our name. it is very high touch. Again, I was speaking of the Clincierge coordinators who have direct interaction with patients and caregivers in planning each of the logistics, communicating with the site, and even with those incidental expenses that may come from the last visit. If I’m the patient, I send them off to my Clincierge coordinator and my Clincierge coordinator makes sure that I get reimbursed quickly.

Daniel Levine: What’s the impact you’ve had on retention and enrollment? Is there any way to quantify that?

Scott Gray: Thank you for that question. Yes, there is. So, what we’ve been able to demonstrate is that where we’ve spoken earlier about a 30 percent dropout rate averaged across all clinical trials, we can demonstrate that the patients we support, we have a well over 90 percent retention rate. That means not having to recruit new patients when some have dropped out mid-trial. So, we can contain the timelines. This is part of how we are enabling the clinical trial performance, improvement by containing the timelines because through our services, patients are less inclined to drop out.

Daniel Levine: And what do you hear from patients? What do they tell you after having experienced the service?

Scott Gray: Well, I was hoping you would ask that question. So, I have two comments that I have in front of me that I will, actually, I’ll just read them out. It’s easy enough. So, from a caregiver, we received this note: “We appreciate working with you. You made a difference. I can’t express how big of a difference you made. Working with you and your team is so much easier and a blessing. Your demeanor and professionalism make the process seamless. Reimbursement is a breeze. The excellent trial, travel support, and prompt reimbursement made it much easier to decide on the course of treatment. You’re a joy to work with.” And then from a sponsor of a 2022 clinical trial: “This is just last year. We want to thank you for all your tireless efforts, which enabled us to dose the first patient in our study. Without your determination to overcome challenges, ability to problem solve, and flexibility to meet our patients’ needs, we would not have been able to reach this momentous milestone.”

Daniel Levine: Scott Greg, co-founder and CEO of Clincierge. Scott, thanks so much for your time today.

Scott Gray: Danny, quite a pleasure to be with you. Thank you.

This transcript has been edited for clarity and readability.


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