The COVID-19 pandemic has disrupted the clinical trials landscape, creating new challenges and accelerating the industry’s shift toward more direct-to-patient services. In a video interview with leaders at World Courier and Xcenda, both a part of AmerisourceBergen, Fierce Biotech’s publisher Rebecca Willumson examines the logistics services and regulatory considerations needed to design and execute a successful clinical trial—both now in the years to come.
“The big story of the COVID-19 pandemic, in terms of clinical trial design, has been a broad shift of clinical trial activity from healthcare settings into the patients’ homes,” said Alex Guite, VP of Services and Alliances at World Courier. Guite said World Courier has seen its daily volume of direct-to-patient shipments increase by up to three and a half times since the onset of the pandemic.
The COVID-19 pandemic has also affected the regulatory landscape and product approval process. “What we’re seeing now is more regulatory acceptance, specifically the FDA, of the use of real-world data for control arms,” said Kim McLeod, director of Prospective Clinical Research at Xcenda. “At Xcenda, we’re seeing an uptake in that type of study design across the board.”
In the interview, Guite and McLeod share insights on the evolving clinical trial landscape, including strategies for implementing a direct-to-patient model and perspective on the future of data collection.
Rebecca Willumson: Hi there. I'm Rebecca Willumson. I'm the publisher of Fierce Pharma, and I'm joined today by Alex Guite, Vice President of Services and Alliances at World Courier, and Kim McLeod, Senior Director of Prospective Clinical Research at Xcenda. Thank you both for joining me.
Rebecca Willumson: So today we'll be discussing trends in the clinical trial landscape, including how the COVID-19 pandemic has affected clinical trials and whether the trends will continue moving forward. So Alex, before we dive in, can you tell us a bit about your background and your role at World Courier?
Alex Guite: Hi Rebecca, thanks for having us. I've been with World Courier for around six years now. And in my role, I've got responsibility for a global strategy, everything we do around our key partnerships and then our fast growing transport and storage service lines, things like advanced therapies, making sure that those new wave of medicine can connect into patients. And then what we're doing around enabling at-home clinical trials, which I think will be super pertinent for our chat today.
Rebecca Willumson: And Kim, can you tell us about Xcenda and your areas of expertise?
Kim McLeod: Thanks, Rebecca. I've been with Xcenda for about seven years and I lead our prospective studies team, which essentially is conducting and designing late phase clinical studies. So that includes post-approval studies, observational studies and patient registries.
Rebecca Willumson: Thank you. So Alex, I'll direct this first question to you. Over the last year, the COVID-19 pandemic has effected nearly every aspect of our lives. Talk to me a little bit about how the clinical trial landscape, in terms of trial design and execution, has been impacted by COVID-19.
Alex Guite: Yeah, of course. The big story of the pandemic in terms of clinical trial design, but then particularly execution, has been a broad shift of clinical trial activity from healthcare settings into patient's homes. And that happened because of a number of shocks that hit simultaneously as the pandemic worsened overall. Supply for healthcare capacity was down. It had to go towards treating COVID. That meant less capacity for clinical trials. Supply of patients, if I can term it like that, stay at home orders, travel restrictions meant it was harder to get to hospitals. And then certainly there was social distancing in the workplace that meant that there were some constraints on frequent of clinical trial manufacturing. So all of that created a huge imperative to enable as many patients as possible to stay on trial, on medicine, overall. We saw a very, very large influx of new direct-to-patient projects through April, May.
Alex Guite: We put together a cross-regional triage group to ensure that we could execute against that volume. And what we've been seeing is up to three and a half times our daily volume of direct to patient shipments during this time. So I'm always making that we're meeting the nurse at the right time, usually for the kind of trials we're supporting, a nurse is involved to make the infusion in the patient's home, and then collecting any blood draws and directing them over to a laboratory for analysis.
Alex Guite: So what that's meant, that effort across nursing companies, logistics, sponsors, and other pharma services companies is that there were many more patients who were able to continue accessing their medicine today, as a result of these efforts than would otherwise have been the case. And I think just to put a bow around all of this, as most trends are being accelerated by the pandemic were preexisting, the same is true here of at-home clinical trials, has been an increasingly growing part of our business for a number of years.
Alex Guite: And the reasons for that are there were a lot of advantages outside of a pandemic. It's easier to recruit. You've removed geographic and mobility barriers to patients involved in a trial. It is a generally more pleasant trial to be part of when you're being treated at home around your normal schedule, particularly for example, in pediatric populations. And all of that means that time to study completion is reduced. And so the economics of it have been a very attractive and increasingly safer number of years to sponsors. And the result of the pandemic, I think, is going to be a feature of our clinical trial design execution for the decades to come.
Rebecca Willumson: So when evaluating whether to implement a direct to patient model, what do manufacturers need to consider, and are there specific products or disease states that you think are more suitable to this approach?
Alex Guite: Yeah, I think that's a good question. I think one thing I would say is in general, we don't see this as being confined to a particular type of intervention or a particular therapeutic area. In fact, broadly, we see all major therapeutic areas represented in the trials that we're supporting. I think that will continue to grow. And I think one of the things that we've seen is we have far more principal investigators, sponsors, regulators, and other participants in the healthcare space and clinical trial space familiar with our model. So then it turns to, what do you need to do to implement a direct to patient logistics model? And certainly that's got to be considered ideally right at the start as part of trial design. I think again, one of the trends we're starting to see is as folk are thinking about starting up new trials, not just in the pandemic environment but potentially beyond that, is they're looking at essentially for a hybrid design, one that includes site-based visits.
Alex Guite: And I think very likely one of the things that was common in at-home health care trials, pre-pandemic, would be that the first dose is administered in a hospital setting or other healthcare setting, so that there's support in case of adverse event. But then the subsequent doses are all conducted at home. I think you'll see a lot more mixed whereby patients will be ready to travel into healthcare settings and others would prefer to receive those products at home. And so one of the roles that I think logistics partners can play in this is thinking through best practices and indeed thinking through the specifics of a logistics model required to support your trial in different countries. And that can include things like why you join a stock investigation, medical products stock, from the site pharmacy, making a local journey over to a patient.
Alex Guite: Or do you use say a central pharmacy model in which a single location is the hub for dispensing products across an entire geography. Those both have pros and cons in respect of what it means by cost profile, risk profile, what it means by way of a burden on the trial site, if the pharmacy is involved in that dispensing action. So a good logistics partner is able to think through and help you plan for that wider supply chain to support the at-home clinical trials. The other thing, just to close on, is look for partners who have great interactivity and ability to connect in with the nursing support, because it's that interaction and actually landing together, if we can term this, the nurse and the drug at the same time is what makes a patient experience seamless and most attractive about the at-home clinical trial model.
Rebecca Willumson: Okay. So Kim, moving over to you, since the onset of the pandemic, we've seen real urgency from all stakeholders and bringing COVID-19 vaccines and therapies, that are shown to be safe and effective, to market as quickly as possible. So how has the pandemic impacted the regulatory landscape and the product approval process?
Kim McLeod: Well, I think it's really interesting. So we're doing primarily late phase studies for drugs that are already approved. But what we're seeing now is more regulatory acceptance, specifically the FDA of the use of real-world data for control arms. So what we're seeing now is instead of needing to randomize patients into control arms for drug approvals, we are using data that already exists and collecting that data.
Kim McLeod: So basically you're using real-world data to put together a control arm for regulatory approvals. So we've got multiple studies going on in that area. And so instead of enrolling these patients and requiring them to be in these studies, you've got the data that already exists and your matching that to what you're collecting in this study. From the manufacturer's perspective, you're really talking about a reduction in time, cost, efficiencies, everything across the board, because you no longer need this control arm with let's say 500 patients because you're able to collect that with data that already exists. So for me, being in the field for a really long time, and now seeing this acceptance of real-world data for control arms is really huge. And I think for us, we're seeing an uptake in that type of study design across the board.
Rebecca Willumson: Given that some of the regulatory changes and the shift to a more virtual environment, how should manufacturers gather and integrate data that supports the product value story, both pre and post launch, and then what's the value of real world evidence?
Kim McLeod: Well, it's interesting. I think for us, we were set up this way already, but what we're doing is a lot of virtual studies. I think that clients and manufacturers need to think more about modifying designs and thinking about studies differently. I think the pandemic has almost forced that. So for something, I think you've got some manufacturers who are more innovative, other ones who are not necessarily as innovative. But what we're doing is we are actually recruiting patients virtually for a lot of our studies, and we were doing that before the pandemic. But what that would include is something like identifying patients within a large healthcare system based on EMR and claims data, and actually recruiting patients directly versus going through a clinical trial site, as Alex was talking about.
Kim McLeod: But basically you're enrolling patients directly, you are collecting their data directly from them, and then you're pulling back in EMR and claims data. So you're eliminating the need for any physician-based clinical research visits, if you will, and having a nice story of what's going on within a patient, especially like in a real world setting.
Kim McLeod: I think you're getting to a place now where you're talking about alternative ways of monitoring, reduction in monitoring. Conservatively, back in the day, you were talking about going out to sites and you're verifying what is in the medical record versus what you're entering into the system. And nowadays, you're looking more towards different alternatives in terms of monitoring, in terms of design, in terms of virtual enrollment, in terms of what Alex is talking about in direct to patient. There's not this requirement to go into the physician office. You can get the medications perhaps directly, you can get telemedicine, you got the telemedicine component in there now, and all of these different pieces, it's almost like we needed to get there, and I think the pandemic's almost forced it if you will. So yeah.
Rebecca Willumson: So Alex, moving back over to you, you mentioned earlier the impact that the pandemic has had on clinical trials with some sites reporting the trial's been put on hold or canceled. So as manufacturers look to restart trials or launch new clinical trials amid the pandemic, what do you think they need to consider?
Alex Guite: Yeah, so we're recording this during the Northern hemisphere winter, and certainly there are trials that are starting up. But it's also a time of continued stress, not just on healthcare, as in most geographies, a greater number of patients are being treated for COVID. Again, that places that constraint on healthcare capacity for clinical trial activity. Certainly when I think about logistics, and this is far wider than just whether or you're doing at-home trial, it extends to all trials, is really getting in touch with your logistics provider and sharing with them project requirements, any requirements very early, so that they can start understanding the supply chain, the temperature control needs in addition to any special instructions.
Alex Guite: And that's good practice in most cases, but particularly so during this pandemic because as well as I mentioned, we've well-covered the clinical trial ramifications, the logistics environment with far fewer freight options. And again, continued travel restrictions. That mean that there are fewer logistics often, particularly in the belly of passenger planes than there were previously. It means that logistics planning is a more time-intensive task and getting that right early will prevent challenges down the road.
Alex Guite: I think the other thing to think through is around flexibility and contingency planning. I think there's no question, pretty much every aspect of a business, the pandemic has highlighted the importance of full contingency planning. Again, something that pharma would often do as business as usual. But I do think it means that it is contingency to think about how the supply chain might pivot if particular routings or manufacturing sites aren't available in particular, when we start thinking about at-home and clinical trials, it comes back to designing whether or not you're going to serve patients from the pharmacy or central dispensing location overall.
Alex Guite: And then I think there's something else that has changed, but was changing anyway, prior to the pandemic as well, which is thinking about how you adapt your clinical trial design to a patient mindset, that in some cases it's more consumer orientated. And I think it's important for us, as seeking to recruit patients again, to specifically consider the additional challenges and concerns that patients will face during the pandemic, or immediately after. One of the things of course, is that many of them have become accustomed to contact-free home delivery services and are continued be concerned about visiting hospitals. And again, there's a role for at-home clinical trials and a bit well-designed logistics around that, that made them feel secure. But all of that needs to be designed into the clinical trial from the get-go.
Rebecca Willumson: So to wrap things up a bit, and I'll ask you both this question and Kim, we can start with you. What clinical child trends do you anticipate will continue in a post pandemic world?
Kim McLeod: Well, it's interesting. I think that we've been having conversations for a while now around real-world evidence and expediting trials and things like that. I really do think the pandemic has forced manufacturers, payers across the board to actually take action and do things differently. So I think before we were talking about it in these situations, you actually had to do it. So whether or not you're recruiting virtually, you're doing enrollment direct to patient, all of these different ways of designing studies and doing things differently, I think everybody's realizing that this is an acceptable way to do it and perhaps a better way to do it. So at the end of the day, I think that you are really reducing drug approval times. So for something that on average may take 10 years from start to finish in terms of drug approvals, really reducing that perhaps maybe even in half by using these methods, whether again, it's virtual enrollment, whether or not you're using real world evidence as control arms, different ways of monitoring, everything across the board.
Kim McLeod: Really, I think for the benefit of the patients, being able to recognize that this reduction across the board in terms of overall drug development. And so again, I feel like everybody was talking about it. This forced everybody to actually do something about it in a very quick amount of time. And as we've done it, I think that everyone's coming to the realization that this does actually work and it's something that we should actually implement moving forward. It's nothing for the short-term. It is the model that will be used as we go forward with drug development.
Rebecca Willumson: Alex, how about you? What are your thoughts there?
Alex Guite: Yeah, I would certainly echo what Kim says there. In conversations with customers, it is very clear that forecast thinking that we're going to be in an environment in which trials are shorter and as Kim says, therefore less costly. And that might mean as well that a different threshold is applied to moving products through phase two, phase three and so forth. I think for me, the key thing that I see staying is the use of direct to patient at-home clinical trials. It is proven, it's shown itself with working pre pandemic, during a pandemic, at scale. And what that means is that there were far more sponsors, investigators and other stakeholders who are used to the model, familiar with its benefits. We did a survey of some of our manufacturer customers at the end of 2020. We found that three and four plan to design at-home clinical trials, as a default into their trial design. And again, that's really about ensuring the border is raised for patient access. So that's going to be a feature that lasts way beyond the pandemic.
Rebecca Willumson: All right. Well that's all the questions that I have. Thank you both for joining me today. I've really enjoyed our conversation.
Alex Guite: Thanks so much.
Kim McLeod: Thank you.