Patients Front and Center: Involving the Patient in Clinical Trial Design

Recruiting patients for clinical trials can be tricky. A 2022 review of 388 clinical trials conducted between 1997 and 2020 found that, overall, only 63% of trials hit their final recruitment target. However, 32% of these trials had to extend their recruitment period to meet that target. Another 22% of trials were able to recruit to within 80% of their final target, with 36% of those trials needing an extension to the recruitment period.¹

Interestingly, 30% of trials reviewed in the study revised their original recruitment target, with 67% of those trials revising it downwards.¹

These numbers illustrate why the industry continues to look for ways to boost recruitment of patients for clinical trials. Unfortunately, some of the factors stopping patients from participating in trials are difficult to overcome. Patients live too far away from trial locations, or they have unique medical needs or life situations that make participating in a trial too challenging.

Patients with valuable lived experience have many insights to contribute to those who are designing clinical trials. However, getting patients involved in this process is still a work in progress.

The value of such an effort is undeniable. A study assessing the financial value of patient engagement in clinical trials finds a patient engagement activity that avoids one protocol amendment and improves enrollment, adherence, and retention increases expected net present value (ENPV) by $35 million pre-phase II and $75 million pre-phase III. This means investing $100,000 in patient engagement can result in a 500-fold return on investment. And this ENPV can equate to accelerating a pre-phase II launch by 2½ years and a pre-phase III launch by 1½ years.²

From the beginning of the conversation

Jenn McNary is co-founder and principal, Canary Advisors, a boutique patient advocacy consulting firm with a focus on regulatory and access patient engagement. She is also co-founder of One Rare, a nonprofit forum designed to meet the needs of young adults living with rare diseases and chronic conditions. Her son, Austin Leclaire, is a member of the One Rare board who’s living with Duchenne muscular dystrophy.

McNary says it’s important to engage with patients in various disease states to seek their insights while a clinical trial is being designed so that it’s going to work for them. Ultimately, they must be comfortable with the study to be able to participate in it, she adds.

“Austin and I together and our family, including both of his little brothers, have participated in clinical trials for well over a decade,” McNary says. “And there’s still a ton of work to be done there.”

According to McNary, showing patients the design and presenting the schedule of assessments is only the beginning. Sponsors really need to get in the weeds and ask specific questions like where the locations of the studies are and what will be necessary to participate, she says.

“Then you listen, you find out from those experts, from those patients, is that going to be feasible? Is that going to be something that they can do?” Mc Nary says. “As a patient and as a family, we always, whether they like it or not, provide direct feedback about studies and about designs and about questions that we might have in the process.”

Citing an example from her and her son’s own experience, McNary says as a more advanced Duchenne patient, her son has an implanted portacath. And a trial he participated in was designed to draw blood from veins. “Well, that doesn't work really well for Austin because it's really easy for him to blow veins,” McNary says.

Leclaire notes there are only two lab tests in the world that can’t be done through a portacath, meaning a blood draw might not be necessary. “We talked to one of the trial coordinators, and we discussed if there was any valid reason why I should do it,” he says. “And we figured out there isn’t, it was just that was the best way they thought of doing it. We eventually talked to them, and we realized there was no reason I shouldn’t use my portacath. So, we came to an agreement that that would be reasonable to use.”

McNary says that if the sponsors had talked to patients in Leclaire’s age group to begin with, they would have discovered that peripheral access for drawing blood is difficult for these patients. “The trial staff was really great about going back to the sponsor and saying, ‘Hey, we have a valid request here and the risk of port infection is much more minimal than the risk of blowing these veins,’” she says. “‘And so we’d like to have an amendment and be allowed to use that portacath.’ And that was an agreement that was made.”

Leclaire says, in his experience, sponsors tend to see obtaining data from the clinical trial as more important than patient experience within the trial. “They’re more focused on that than necessarily how the patient will be able to go through the trial and what their experience will be,” he says. “It’s really important to focus on how we’re getting that data from the patients in the most comfortable way possible that works for them — especially with traveling, because for a lot of these clinical trials, we have to travel to go there.”

Leclaire notes a lot of his testing in trials doesn’t do as well when he’s been traveling. “The port’s important because it’s hard to really hydrate when I’m on the plane because I take a lot of meds that tend to make me have to use the bathroom a lot,” he says. “Some of those things need to be thought of as well. Like with clinical trial design, it’s good to make sure that you have at least a day of time to recoup and get ready for the testing.”

Make sure there’s enough support

McNary says for her, patient centricity means putting the end user at the forefront from the beginning, when a sponsor is planning the clinical trial.

“One of the things we’ve noticed as a family and then we’ve implemented at Canary Advisors, through our concierge program where we support sponsors with patient travels and needs throughout their clinical trial engagement, is that some of these families need some additional support or information,” she says. “Things like … how do you access a place to pick up medications if you need them? What hotels have roll-under beds? We have surveyed every hotel in this area of this clinical trial to make sure a Hoyer lift can get under the bed so that when we’re staying here, we have access to things like that.

“It involves really thinking about the patient as a whole person and thinking about the caregivers as a whole family, siblings, parents, the parents both at home and on site for a clinical trial,” she adds. “Thinking about them when you’re planning ahead and making sure that you’re lessening the burden to the best extent possible.”

Getting ‘Dr. Mom’s’ feedback

It can also be helpful for sponsors to talk with people close to the patient for their insights. McNary notes that her son doesn’t always have the focus to give insights on clinical trial designs for Duchenne patients. 

“That’s somewhere I can pick up and as a caregiver representative, I can help out,” she says. “He may also have friends or caregivers or care partners from the past. I once ran an advisory board for ALS with almost entirely home nurse caregivers to talk about medicine administration and what the best routes were and what they were currently doing. So, where there’s a will, there’s a way. And just throwing up your hands and saying there’s no way to collect patient insights or patient input is not the way to do it because there’s always a way, and there’s a return on that investment.”

McNary gives an example from a previous Duchenne study. Designed for very young male patients, often with attention-deficit and sensory-overload issues, the study was requiring them to remain in an MRI machine for well over an hour.

“And parents were talking with a pharmaceutical company representative and [the representative was] saying, ‘Gee, we cannot recruit this study,’” she recalls. “‘We keep having these screen fails and we can’t figure out what the problem is.’ And the problem was that either the site was looking at this patient doing loops around a room, unable to sit still to even while their parents listened to the study design, or the parent would hear something like he has to lay still non-sedated for over an hour in a machine for an imaging endpoint. And they went, ‘There’s no way my kid’s going to do that.’ And they left.

“We were able to share that insight. And thank goodness they didn’t just continue on for a year trying to recruit that study,” she continues. “They changed it, and I think they ended up doing a one arm image for a much shorter period of time. Then the child could be entertained with a movie and it worked. But they would’ve saved money if they had done an ad board and presented that as a potential endpoint. They would’ve heard from all of us that have had children of that age that, ‘Hey, that’s not going to work for this age group.’”

Gene Jay, head, clinical trial solutions for the pharmacy care and benefits solutions provider Evernorth, refers to that aspect as “Dr. Mom” data. “There’s patient and family caregiver information that needs to be ascertained for data, which is important, I think,” he says. “You’re not going to find a medical claim or an EMR anywhere that says, ‘Well, my kid is ADD, and my kid’s not going to be able to sit still for 15 minutes to go through that study.’ That's not going to show up on a claim anywhere, and it probably is not going to show up in EMR. We’ll see a claim for ADD or some other conditions, but it really doesn’t give insight into the actual patient.

“Now, I don’t live in that third domain, the Dr. Mom domain,” he adds. “It would be great if we did. I’ll say we don’t have that, and a lot of institutions really don’t have that data in detail, but we do have claims data, and with claims data we also have demographic data, and we have social determinants of health information, which can be also very, very important.”

Jay says Evernorth becomes involved in a lot of rescue trials when there are not enough patients recruited to participate. “If you don’t put the patient front and center, guess what? You may have a very difficult time recruiting as many patients as you want,” he says. “And I hear all the time from our plan sponsors and pharmaceutical providers that, boy, this trial is running over, it’s taking much too long and we’re having a difficult time recruiting patients. Well, I think we have to build in patient centricity right up front in that trial design.”

Sources:

¹ Jacques RM, Ahmed R, Harper J, Ranjan A, Saeed I, Simpson RM, Walters SJ (2022) Recruitment, consent and retention of participants in randomized controlled trials: a review of trials published in the National Institute for Health Research (NIHR) Journals Library (1997–2020). BMJ Open, 12(2), e059230. Available from: https://bmjopen.bmj.com/content/12/2/e059230 [Accessed Sept. 27, 2023].

² Levitan B, Getz K, Eisenstein EL, Goldberg M, Harker M, Hesterlee S, Patrick-Lake B, Roberts JN, DiMasi J (2018) Assessing the Financial Value of Patient Engagement. Ther Innov Regul Sci, 52(2), 220–229. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933599/ [Accessed Sept. 27, 2023].