Putting the Patient at the Center of Rare Disease Clinical Trials

May 7, 2021

The recruitment of patients for rare disease clinical trials can be challenging because of issues such as small patient populations and their geographic dispersity, but the failure to take a patient-centric approach in designing trial protocols can add to the difficulties sponsors face in conducting such studies. The Center for Rare Diseases at PRA Health Sciences recently issued a toolkit focused on patient-centric trial development for sponsors, participants, and advocates. We spoke to Scott Schliebner, senior vice president and head of the Center for Rare Diseases, about designing patient-centric clinical trials, why it matters, and what sponsors can do to stay focused on patients.

Daniel Levine: Scott. Thanks for joining us.

Scott Schliebner: Thanks for having me. My pleasure to be here.

Daniel Levine: We’re going to talk about patient-centricity, clinical trials, and how sponsors can structure studies with rare disease patients in mind. I’ve never met a biopharmaceutical company that didn’t describe itself as patient-centric. I think rare disease companies tend to be a bit more sincere about this than the industry as a whole. How good are companies at being patient-centric, particularly when it comes to clinical trial designs?

Scott Schliebner: Interesting question. When you look around the industry at small biotech companies and large pharma and every shape and size in between, I think a lot of companies certainly pay some lip service to being patient focused or patient-centric. Some companies are certainly doing a better job of that than others. Some companies are literally putting their money where their mouth is. That’s great to see. I think the trends are really positive in the way that we’re seeing companies move towards being patient-centric. We’ve been evangelizing about the need for this for several years and I do feel there’s great momentum. More and more companies are actually walking the walk and not just talking the talk.

Daniel Levine: Why does it matter? What’s the case for drug developers to take this seriously?

Scott Schliebner: Rare diseases certainly pose a unique scenario that has some particular challenges and hurdles to them. Really, if you zoom out from there to really any part of drug development, any disease state, or any therapeutic area, the need to be able to think about our ultimate stakeholders and end users is really what’s important here. There’s a lot of metrics and data, and I could share a couple of facts today, but in the rare space those challenges become amplified and the hurdles become even a little higher to get over. There’s a lot of specific needs to think about patients first and foremost. Whether it’s the diagnostic odyssey that they go through, the challenge in finding appropriate investigators, or finding where these rare patients are and being able to connect them to clinical trials, investigators, and investigative sites. It’s challenging. When you overlay rare diseases on top of a challenging and somewhat archaic drug development paradigm, the challenges become extra complex and exponential. This requires us to think differently and operationalize these clinical trials in a different way.

Daniel Levine: You talked about hurdles, how big a problem is patient enrollment and retention in rare disease clinical trials today?

Scott Schliebner: It’s a problem, COVID notwithstanding. Right now, when you look at drug development overall, not just rare diseases, we need more patients for more trials every single year. So for 2021, we need 40 million patients worldwide for over 300,000 clinical trials. That’s a staggering number that will grow again next year and the year after that. Rare diseases are certainly a subset of that. We now know that about half of all clinical trials are now behind schedule due to enrollment. We also know that because of the way the paradigm is set up, where clinical trials open at clinical sites and patients typically travel to and from that clinical site, more than 30 percent of patients drop out of studies. Retention is an issue in every indication. Not to be a broken record, but when you move into the rare space, those challenges are amplified. We’re talking about children, caretakers, and entire families and just given the reduced prevalence of rare diseases, people with those diseases don’t necessarily live right next to an academic medical center that might house a trial. So, we have to be creative. Necessity being really the mother of invention here, in terms of pushing us to do something different.

Daniel Levine: What are the primary reasons that sponsors fail to enroll the patients they need in a timely manner or lose them during a trial?

Scott Schliebner: It really starts with the traditional drug development paradigm that has been largely unchanged for the last three to four decades. We develop a clinical protocol and I like to say it’s “in a conference room in New Jersey,” because the protocol is developed somewhat in a bubble insulated from external stakeholders. We push those studies out to clinical sites. Then, the clinical sites look at these studies and say, “I guess we can enroll the study but it would’ve been nice if we shared our feedback first,” and then the sites then move out to patients. You have this stepwise approach where the study is developed and designed in a manner that is very disconnected from the end user, the patient who will actually enroll in it. We pushed these studies out and then we realized there’s all kinds of barriers and challenges, and we have to work to overcome them. Part of that is the structure of the paradigm of go to clinical sites, clinical sites find patients, patients have to drop everything and travel to and from sites. Those paradigms are a challenge to patients. Patients say that the biggest burden to participating is travel to and from a clinical site. This the most significant burden for rare disease patients and that’s at the core of what we need to work on.

Daniel Levine: PRA Health Sciences is a contract research organization. It also runs the PRA Center for Rare Diseases, which is done in collaboration with rare disease patients. The center recently released a free toolkit to identify and mitigate risks to rare disease clinical programs. Why did you decide to do this? What problem were you trying to address?

Scott Schliebner: The problem we were trying to address is figuring out ways to overcome these hurdles that we’re talking about for clinical studies by going further upstream to provide tools to sponsors and patients alike upfront prior to studies being developed, finalized, and pushed out to clinical sites. It is important to educate, inform, call out those risks, and call out those hurdles in a study before we move further downstream to where we’re running and wondering why people aren’t enrolling. This tool was enabled and built with guidance by patients to help patients, and biotech and pharma trial sponsors look at their studies from a patient’s perspective. We hope to be able to say, hold on, before we finalize this and move out to clinical sites, we’re hearing that X, Y, and Z might be a big barrier. Let’s see if we can make some changes to make it a little bit more patient friendly.

Daniel Levine: There are four components to the toolkits. Let’s run through each of those and tell me how they work and what do they do. The first is a patient-centric protocol risk assessment tool. What is it, and how should it be used?

Scott Schliebner: The first part is to take a look at a clinical study. If you work in clinical trials and clinical protocols are part of your day-to-day vocabulary, the core of that clinical protocol is what we call a schedule of assessments or a schedule of evaluations. That schedule of assessments is a grid that outlines what, and when, is going to happen. You’ll often see these by week one, two, three, all the way out to week 52, and then you’ll see a long list of things like, a physical exam, an invasive procedure, a scan, or an assessment. “In a conference room in New Jersey” we map out every data point that we want and we bring together our chemists, our translational scientists, and our physicians. We all come together and say, “These are all the data points and measures that we want, and if we could get these at all of these different time points that’d be a more robust data set.” When you do that and look to build this massive monolith of data, we’re not necessarily thinking again about what is realistic for patients to participate in. The patient-centered protocol development tool enables us to pressure test a couple of these things upfront and to assess the level of burden and how much of a hurdle these assessments we’re looking at are before we finalize it. There’s a way to play with some of the levers up and down in a protocol to see how impactful they might be on a real person or a patient. So, this tool is a tool for sponsors to try to assess what you’re trying to do and hopefully be able to make some adjustments before it’s too late.

Daniel Levine: The second is a rapid participation burden survey tool. What is that, and how is it used?

Scott Schliebner: This is a tool for those sponsors that talk about being patient-centric or talk about being patient-focused. Many of our colleagues and clients don’t know how to reach out to patients, how to speak to patients, or what’s appropriate. We’ve developed a way for them to quickly be able to reach out to patients via a survey tool to ask what’s most important to a patient, what would be an endpoint that would be relevant to their disease and their experience, what kind of physical limitations do they have, or what are some things they might be comfortable doing or what might be too much to ask. It’s a way to create a dialogue between a sponsor and a patient in a safe, controlled, and somewhat confidential manner to get patient feedback and input upfront. It helps the sponsors be a little more patient-focused.

Daniel Levine: The third component of the toolkit is a patient involvement value dossier. What is this, and what’s its purpose?

Scott Schliebner: The purpose of this is for those colleagues of ours who think being patient-centric or patient-focused is a good thing. Maybe it strikes some sense of altruism in you and you like the idea of it. At the same time, we all work for organizations that have top and bottom lines that they are focused on. This dossier around value shows that not only is involving patients the right thing to do, it makes financial sense to include patients in the process and incorporate their input. This impacts some of the challenges we talked about earlier: enrollment and retention. It allows clinical trials to be more realistic for people to participate in. If you’re having a hard time internally gaining support and consensus around why we should move to a more patient-focused approach, this dossier outlines some evidence around why it’s financially impactful. Hopefully it can speak to anybody whatever their motivations might be.

Daniel Levine: And the final part, I think would be of particular interest to any patient who’s considering participating in a clinical trial. This is a guide for patients and caregivers. It provides a rather full set of questions they should ask before participating in a study. Are there things patients in general don’t understand about clinical trials that they need to?

Scott Schliebner: I think that’s a fair statement. We’re trying to encourage a little more dialogue. We’re encouraging sponsors via tools to be able to reach out and solicit patient input and feedback on a study. At the same time, this participant guide informs patients. It’s good for patients who may not know a lot about clinical studies or may not know a lot about the drug development industry. It informs them and provides a guide for questions they could ask. If they’re thinking about participating in a clinical study, it allows them to have a sense of what’s realistic. As a patient, what can I ask for from a sponsor? Is it okay to ask for travel reimbursement? Is it okay to ask for some support and what are the options available to me as a patient? Could I have a nurse come to my home to support a blood draw, as opposed to going into a clinic? Some patients might not even know that’s an option. Putting that opportunity in front of them might make the difference between them participating or not. It’s the backend of trying to support dialogue between industry and patients.

Daniel Levine: I suspect there are patients and caregivers who are very anxious to participate in a clinical study, particularly when they have a condition where there are no treatments available. What types of questions should patients think about before consenting to participate in this study?

Scott Schliebner: That’s a great question and you have some good perspective on this yourself. There is, of course, a big range of patients. The level of education or exposure people have had to industry and clinical research varies quite a bit. In this new kind of world we’re entering, COVID has served as such an incredible accelerant for us making a change to this somewhat archaic paradigm that I’ve alluded to. It’s forced us to leverage technology and new tools to keep things going. With that, this paradigm now is shifting a bit to the benefit of patients as it will provide more opportunities. At the same time, with the change occurring rapidly, there are things available to patients that maybe weren’t available 12 or 24 months ago. For example, a lot of the clinical studies that we’re involved with in the rare disease space, most of them include some type of telehealth component. The ability to interact with your physician remotely, from the comfort of your home, as opposed to flying or driving to a clinic and all the time and hassles associated with that. Those are hassles and inconveniences, but when you overlay that on top of a rare disease patient who’s already struggling with a chronic life-threatening illness, or perhaps there’s a child that’s being taken care of with such an illness, the barriers all become exponential. Some of the opportunities available to patients these days are things like telehealth. I alluded to home health care nursing earlier, which essentially moves some aspects of a clinical site to a patient’s physical home. If the patient is comfortable with that, or would prefer it, it can remove a lot of challenges from that patient’s plate. We can minimize the burden so that they can participate and they can stay in the study. We’re trying to arm patients with the possibilities that now exist and let them know that there are options that might not have been available to them in a traditional old school paradigm.

Daniel Levine: One of the longstanding complaints you hear from patient advocates with regards to clinical trials is that they’re consulted too late in the process, after the trial design has been completed. They may be frustrated that studies don’t consider endpoints they believe to be meaningful, or that trials are too onerous in their design for patients to participate, whether it’s due to travel or other demands. How do you see the industry changing? Has it become more enlightened about the value in working with patients early in the process?

Scott Schliebner: There’s good trends this way. I think we’re moving in the right direction. Again, COVID has been helpful in this regard. Some of us have been evangelizing for the need to include patient inputs, and think about the studies you’re asking people to participate in. This old mantra of “if you build it, they will come,” is it really true anymore? Patients are more educated and they have choices. There’s competition out there. Certainly, patients are altruistic and they’re looking for a new treatment that will help them with their disease, but they also have choices and preferences. They understand that there are options available to them and that we can be thinking smarter and this age old paradigm can be shifted to be more patient friendly. I think sponsors are now seeing this more. I think sponsors have seen that COVID has required us to operate a little differently to get things done during the pandemic. As we come out of this, hopefully soon, you see the movements, like the hashtag, never go back to old paradigms. I think people are seeing the light and it will be really challenging to revert back to older models when we’ve seen that we can operate in a smarter, more patient friendly way. I’m really optimistic. We’re also supported by agencies like the FDA that are encouraging a more patient-focused drug development mindset and approach. It’s long overdue and I would never have bet a pandemic would help us with this effort, but you know, we’ve seen some good progress as a result.

Daniel Levine: Scott Schliebner, senior vice president and head of the Center for Rare Diseases at PRA Health Sciences. Scott, thanks so much for your time today.

Scott Schliebner: My pleasure. Thanks for having me.


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