Bringing the Trial to the Patient

Advances in communication, information, and monitoring technologies have enabled the advent of decentralized clinical trials, but the COVID-19 pandemic crystalized the interest of regulators and trial sponsors. In fact, most biopharmaceutical companies today now expect to use elements of decentralized clinical trials in studies going forward. Science 37 is providing a software platform to enable decentralized clinical trials and offering a range of services on top of that to meet the needs of trails sponsors. We spoke to Jonathan Cotliar, chief medical officer of Science 37, about the move toward decentralized clinical trials, how technology is changing the types of data that can be gathered, and how it is forever reshaping clinical trials.

Daniel Levine: Jonathan, thanks for joining us.

Jonathan Cotliar: Thanks, Danny. Thanks for having me.

Daniel Levine: We’re going to talk about Science 37, decentralized clinical trials, and how technology is changing the way we’re gathering data. I’d like to start with the landscape and the confluence of developments that are both driving a move towards decentralized clinical trials and accelerating that. Perhaps we should be clear for listeners and start with what a decentralized trial is and how it differs from traditional studies.

Jonathan Cotliar: I think that’s a really good place to start. Decentralized trials have come into the forefront with COVID. Our organization started in 2014. So, when we first started engaging in decentralized trials, there was quite a lot of skepticism about the approach. It’s become, I think, more mainstream as a mitigation tool. Decentralized clinical trials conduct was a necessity as sites were shut down over the past 18 months or so. I think, in a nutshell, the concept of a decentralized trial is not depending on sites to conduct or execute a clinical trial for the purposes of drug development and drug approval. It doesn’t necessarily have to be that all the visits in a decentralized trial have to take place in somebody’s home. In most cases, everybody’s concept of what a decentralized clinical trial means is that there’d be an equitable split of study visits, which historically have taken place almost exclusively in hospitals or clinical settings, and now migrating some of those visits into a participant’s home. Of course, the stars all have to align. You have to have an investigational drug that’s safe. You have to have end points that make sense in terms of identifying whether a particular intervention is actually improving a given condition. You have to make sure that patients are aware that they have a certain diagnosis and that you can confirm eligibility on the grounds of patient narratives and then corroborating it with the review of medical records. Many things we typically take for granted when they occur in the context of a traditional clinical trial, like being in-person so you can know whether it’s actually the person it’s purported to be who’s enrolling for a trial, consenting them for a trial, doing blood draws, and doing all sorts of assessments. We can break down each of those activities and figure out whether it’s amenable and safe to do those in a patient’s home. Again, in summary, it’s going from a place where everything in a traditional trial is taking place in a clinic or a hospital and breaking those down and seeing which activities can be conducted in somebody’s home.

Daniel Levine: You alluded to the impact COVID 19 has had on decentralized clinical trials, and I do want to talk about that. Before going there, what are the different elements that have fallen into place to enable decentralized trials? What have been the long-term drivers, what are the problems in traditional site-based trials that this can address?

Jonathan Cotliar: That’s a great question. I think that the underlying motivation that a lot of sponsors have used to think about decentralized clinical trials is, if you look historically at traditional brick and mortar trials, there is a tremendous amount of enrollment challenges—largely because geography constitutes probably the single greatest variable as to whether enrollment and ultimately the execution of the clinical trial is successful. There’s a lot of good statistics that have been published over the last decade or two. The one that we typically look to quote is, if you take somebody off the street and surveyed a hundred people and say, ‘hey, there’s a clinical trial, it’s safe and we’re going to learn a lot of things, it has potential benefits for you’, nearly 90 out of 100 will demonstrate interest. The problem is that out of that 90 percent who are interested in a clinical trial, about 70 percent of those folks live two hours or more away from where the nearest clinical site is located. Even in cases where there’s a tremendous amount of interest to participate in a clinical trial, geographically speaking there are limitations. So, that type of travel, to and from a site, not just one time, but over the entire course of a trial, and getting arrangements for childcare and other dependent care and taking time off from work is a nonstarter. That really is a large contributor as to why so many clinical trials are delayed or fail to enroll all together.

Daniel Levine: For rare disease, clinical trials present their own set of challenges. How has the adoption of decentralized clinical trials changed these studies?

Jonathan Cotliar: Similar to common conditions, rare diseases and the geography associated, where participants and their caregivers live in relation to where the clinical trials are taking place at sites, is probably the biggest variable as to whether a trial will ultimately be successful. On top of that, compared to more common diseases, for rare diseases, the sheer numbers of people who have conditions X, Y, or Z, is so much lower that your total denominator of available patients who’d be interested in a study is just so much lower. So, that further amplifies the problem of geography. Look we cut our teeth on a rare disease trial and it’s a huge component of our business because we’re so mission focused on enabling people to participate from anywhere in clinical trials. From our standpoint, the rare disease category is something that drives our organization and brings a lot of sponsors to the table to work with us in embarking on studies for rare disease patients.

Daniel Levine: Think of the confluence of technology, smartphones, cloud computing, ubiquitous and inexpensive monitoring devices. How have these enabled what you’re doing with decentralized clinical trials?

Jonathan Cotliar: Great question. I think that the fact that in our pockets we’re all carrying devices that allow us to do everything from hail a ride to the airport, order food, buy homes, and arrange our vacations. There’s an expectation now that, not just standard of care in healthcare delivery, but also participation in clinical trials needs to echo what people typically expect in any given day for their workflows, whether that’s professionally or personally. So, there’s a certain expectation now that technology will enable participation in clinical trials in the same way that technology enables so many of these other things. We hear that directly from patients. They don’t want to travel to sites for a blood draw or to be weighed and measured because those are things that, in the world we live in today, are delivered at a reasonable price for patients in their home. Those expectations now through technology are really no different on behalf of patients. That’s been a huge driver to get drug companies to move in this direction. Of course, patients have the loudest voice and I think that’s been hugely powerful.

Daniel Levine: We touched on COVID, but how did COVID accelerate this move towards clinical trials? How did it change the landscape?

Jonathan Cotliar: I sort of alluded to this earlier. When we first started in 2014, we basically created the category of decentralized clinical trials. We were committed to that as an organization. At that time, there was a lot of skepticism on behalf of the industry and justifiably so because it’s a new way of doing things and our industry doesn’t tend to move tremendously quickly. Back then, most of what we did was blending our interpretations of state and local telemedicine laws with guidance documents on the books provided by the FDA that largely were dictating trial conduct at brick and mortar sites. That was an interesting proposition to undertake. Some biopharma companies were really innovative. Others yearned to innovate, but were still skeptical of the DCT model. I think what happened with COVID is we saw the FDA and its European counterparts, the EMA, issue guidance documents in March and April 2020, where they called out specifically the use of decentralized clinical trial conduct, virtual visits, telemedicine as mitigation tools to provide continuity for patients who were soon to be enrolled in clinical trials before COVID hit and those that were already enrolled in clinical trials. That provided the kind of rocket fuel for the entire industry to say, we have to move to decentralized clinical trials because the sites are shut down. We can’t bring patients reasonably safely into sites without PPE being given to them. We can’t even get PPE for our own medical and nursing staff. So, let’s just keep patients at home and see what we can do using technology and decentralized clinical trial companies like Science 37 in order to keep patients safe. That’s really, what started giving some safety to organizations who may have been a little bit more resistant to incorporate DCTs into their normal tools for execution.

Daniel Levine: I think of this kind of push and pull between industry and regulators. Who’s been more ahead of the curve on this one? Has it been regulators or has it been industry?

Jonathan Cotliar: It’s funny you say that because we’ve had the luxury of being able to meet at a policy level with the FDA on several occasions over the past few years. What I would say is, between those conversations and the conversations that we routinely have with some of our collaborators and sponsors, the sponsors are always saying that the FDA would never go for something like that. Yet, when you speak to the FDA directly, it’s like, no, we want to go for this and we want to innovate. So, tell your sponsor partners to push for this and we’ll move forward. I’d have to say if I was flipping a coin, I think that the FDA has been quite progressive. In many cases, so have our global biopharma partners. In some cases, there’s been some reticence on behalf of the pharma partners to move forward based on assumptions that the FDA would be a little bit more conservative than they actually are.

Daniel Levine: Having been through this year of COVID, did anything change in perceptions of decentralized trials or is industry more open to this now? Do they see it works?

Jonathan Cotliar: I think organically, even without COVID, I think we were on a path to ultimately get to more widespread industry acceptance. There’s a soon to be guidance document that the FDA is going to be publishing on decentralized clinical trial conduct, as will ex-U.S. regulatory counterparts around the globe. I think what COVID did is really accelerate that adoption and that acceptance in a way that ultimately would have happened, but probably sped up the process by at least a couple of years.

Daniel Levine: We hear a lot about patient centricity. How has this changed the view on patient centricity in clinical trials?

Jonathan Cotliar: I don’t know if it’s changed it. I think, if anything, it’s reinforced that there’s a delivery model that centers on the patient’s own personal schedule, that’s centered around where patients live, and not necessarily on dependence on the site. I think it’s probably just reinforcing what we already knew was going to take place with respect to the transformation to a more patient centric decentralized model, but just expediting the path to get there. I do think that there had long been recognition that it’s challenging to ask patients to put everything in their personal lives on the back burner and drive to sites repeatedly over the course of their involvement in a clinical trial. I think technology can enable a lot, but it can’t enable somebody to be teleported to a clinical site if they live a hundred miles away. So, bringing everything into the patient’s home had long been aspirational, but now we and others are doing that in a way that feels very comfortable. In many ways, I think this will be the model or the paradigm moving forward for many trials.

Daniel Levine: We’ve also heard a lot about real-world data and the desire to incorporate more of it into the drug development process. Is this technology changing the types of data we can gather in a clinical study?

Jonathan Cotliar: For sure. Certainly, in the context of an interventional traditional phase 2 or phase 3 trial, you can migrate some of those procedures and assessments and endpoint data collection that would typically occur in the clinical space or the hospital, and now you can deploy a mobile nurse into somebody’s home and do everything from vital signs to biospecimen collections to some endpoint data collection through telemedicine. Over the last seven years we’ve been doing that. Even if you look at just the way registries traditionally have been built, you can think about somebody who has de-identified data within a registry, and all of a sudden you can tokenize their data, obviously after explicit approval from a consenting patient, you can add in things like medical records or wearables, and then you can do telemedicine check-ins and have nurses come into the home and draw biomarkers, and you can really improve the data set and the quality of the data within a registry to better inform drug development. Also, better understand what patient journeys are in a way that we’ve never been able to before.

Daniel Levine: One of the challenges with a clinical trial that uses multiple sites is getting consistency in the way data is gathered or measured. I’m wondering if decentralized clinical trials amplifies that issue, or if you’ve discovered other limitations or obstacles.

Jonathan Cotliar: Yes, there’s always going to be obstacles. Frankly, there are certain indications and certain endpoints that cannot be, at the present time, migrated successfully in a validated way from the clinic or the hospital space. The way I think about that is you take the UPRS, which is a traditional end point for Parkinson’s disease, that is a really challenging endpoint because, among other things that go into an overall scoring system, you need an experienced neurologist who can detect nuances from one patient to another with respect to rigidity. To be able to do that through telemedicine is obviously challenging because you have to lay hands on a patient. Even in a clinical scenario how one experienced neurologist grades rigidity compared to another there’s always probably going to be issues with consistency. If you think about it from a decentralized clinical trial perspective with objective endpoints, and objective endpoints might be blood-based, like a hemoglobin A1C for a type 1e or a type 2 diabetes patient, you can make the case that it doesn’t really matter if the blood draw is taking place in the home or in the hospital if you’re using the same central lab to process that blood specimen and arrive at an endpoint. Probably not. The same would hold true with endpoints that rely on imaging where the images themselves can be reviewed in a de-identified way by a central group of raters and to standardize the way we employ certain criteria on the basis of reading those images. Those are the types of endpoints where taking a decentralized approach makes a lot of sense, because there really aren’t many site-based dependencies to engage in the collection of those endpoints. Again, every trial is different, but I think that there’s enough out there to make conduct in a decentralized fashion, not only compelling, but the right choice in the name of patient centricity.

Daniel Levine: Let’s talk about Science 37. If you go to the website, it looks more like a technology company than say a CRO. What’s the product, who’s the customer, and what’s the business model?

Jonathan Cotliar: I would say that the way we’ve positioned ourselves is as an operating system. Basically, the backbone of that operating system is the technology that we built. But really the take home message of what we’re trying to achieve through this operating system is enabling universal access to patients and also to providers. Over the course of the seven years that we’ve been in existence, that construct has allowed us to enroll faster, retain patients at a greater clip than what’s historically been published in traditional brick and mortar research, and also engage with a more representative patient population. Again, if the dependency is to drive to clinical sites, we know that there are certain communities that are located in proximity to clinical trial sites and other communities that are far removed. That typically is why we see, at a socioeconomic and ethnic level, a lack of diversity. It has to do with geographic proximity to where the clinical trials are taking place. We use our technology and our operating system, and then we have what we call our specialized networks of patient communities, telemedicine, investigators, mobile nurses, remote coordinators, and connected devices to allow for universal access in clinical trials.

Daniel Levine: Are you enabling decentralized clinical trials or do you have more of a hands-on role in helping run them?

Jonathan Cotliar: Both, I would say. We check all the boxes. We have a variety of different offerings. In some cases we function as a site, I’ll be at a site without any geographic restrictions because we have these networks of broadly licensed nurses and telemedicine investigators. So, we have the ability uniquely to basically go into the living rooms of anybody who’s otherwise eligible for a study and gives consent to participate in a clinical trial. That represents the bread and butter of what we’ve done over the last seven and a half years, mostly in the phase 2/phase 3 interventional space across a variety of different therapeutic areas. We also provide technology for some of our customers. So, that might mean that they’re using our platform to help them gather evidence, whether that evidence generation is taking place in a clinic or a hospital or in somebody’s home. In cases where on top of the technology, organizations or sponsors want to work with us and leverage some of our other specialized networks, we support them in that way in a modularized fashion. It really depends on the needs of a given sponsor or a CRO or a particular trial. We can help enable either a little bit or a lot of decentralized clinical trial conduct.

Daniel Levine: Have you been able to quantify the benefits you deliver either in terms of time to enrollment, cost, retention, or in other ways?

Jonathan Cotliar: Yes. We use all those metrics. Sometimes we’re able to deliver on shorter timelines from first patient to data lock. Sometimes we’re asked to engage in clinical trials explicitly for the purposes of engaging with communities that have traditionally been underrepresented in clinical trials. In some cases it’s both of those things. On the whole, if you look at the enrollment metrics, the retention metrics, and the diversity metrics they tend to exceed what we know historically has existed and has been published at the site level. We certainly like to think that a lot of that has to do with the way we design and deliver studies. I think, if you can bring trials to patients where they live, instead of requiring them to travel to sites, in many cases that unlocks some of the historical challenges we’ve seen with drug development and clinical trials.

Daniel Levine: As you think about the future of clinical trials, do you expect decentralized clinical trials to become the norm? Do you think that future trials will always include an option?

Jonathan Cotliar: Yeah. I don’t think that in the future traditional brick and mortar conduct will go extinct. That would be silly. There is certainly still a need to engage in clinical research at brick and mortar sites. It’s an important component of drug development. There’s a lot of trust engendered on behalf of patients and their doctors who are at sites. Our intent is not to circumvent sites or to make them extinct at all. I think whether it’s a mitigation against the pandemic, whether it’s a few visits or even all visits for certain trials where it’s a good fit, there is a place for keeping patients at home in cases where it’s safe to do. So, decentralized clinical trial conduct is here to stay. The extent of DCTs in any given trial, or across a number of trials in any given year, will certainly grow. I don’t see that as competing with traditional conduct, I see them as synergistic. From our standpoint, and we’ve done this in a lot of our trials, you have sort of juxtaposed traditional brick and mortar sites with what we call our Meta site, which is really nothing more than a virtual cohort engaging in a clinical trial from the comfort of their home. The two together deliver the best of what historically you’ve appreciated about clinical research at the site, but also allow us to recruit and enroll patients from the white spaces and outside of your typical geographic boundaries, where people are able to commute to clinical sites. So, I see it really just a blend of both.

Daniel Levine: Science 37 became a public company via merger with a SPAC, with other financing efforts around that you had a $1 billion plus market cap and $250 million to fund your activities. What’s the plan for growth here?

Jonathan Cotliar: I don’t think the plan for growth is going to deviate too much from what we’ve done for the last seven years. Frankly, from my standpoint, being a public company is great in many ways as it’s the fruition of a tremendous amount of work done by many people that have contributed to the success of the organization. Our focus is on delivering clinical trials in a way that ensures patient safety and generates high quality data. I don’t see that trajectory changing at all now that we’re a public company. I think we’ll just have the added benefit of continuing to be able to scale our company globally in a way that guarantees that patients and providers, all across the globe, have access to Science 37 capabilities and can be part of decentralized trials on a global level.

Daniel Levine: Jonathan Cotlier, chief medical officer of Science 37. Jonathan, thanks so much for your time today.

Jonathan Cotliar: Thanks so much, Danny. It was great.

This transcript has  been lightly edited for clarity and readability.