Virtual Clinical Trials – Care from Anywhere

(This is an unedited transcript. For accurate quotes and presentations, please refer to the full-event video.)

Emily Gibb:

Okay. Hello, this is Emily Gibb from GSK. I want to thank the Alliance for Health Policy for hosting this conference and for bringing forward the voice of the patient. Patients, caregivers, and communities, in the US and around the world, rely on the medicines and vaccines, that GSK manufactures, and we take this responsibility very seriously. The pandemic has severely affected routine medical care in the country. There’s been a steep decline in immunization rates among adults, and many patients have had to delay cancer screenings. It is critically important that we educate patients about the importance of prevention and that we work together to help patients overcome any barriers they may be facing to getting their routine medical care. For example, for Medicare Part D patients who may need a vaccination, those patients can sometimes experience up to $100 in cost sharing. The Protecting Seniors Through Immunization Act would eliminate this barrier.

Emily Gibb:

We also need to work together on innovative financing models that recognize the value of one-time, curative therapies to treat significant and debilitating diseases like cancer. Together I’m optimistic that we can create a stronger healthcare system, now and after the pandemic. Thank you so much.

Kathryn Martucci:

Hello. And thank you for joining the third session in the Alliances 2020 Signature Series Summit on the Voice of the Patient. I am Kathryn Martucci, Director of Policy and Programs for the Alliance for Health Policy. For listeners who are new to The Alliance, welcome. We are a non-partisan resource for the health policy community, dedicated to advancing knowledge and understanding of health policy issues. And throughout this three-day event, we are examining how the patient voice is collected, how it supports shared decision making, and how it’s leveraged in policy translation efforts to improve patient experience and build healthier futures. I want to take a moment to think our 2020 Signature Series sponsors. You should see them on the screen, and we really thank them for their support in making this summit happen.

Kathryn Martucci:

I also want to highlight some upcoming sessions where we will continue to explore the Voice of the Patient. In particular please join us today at 12:00 PM for a panel discussion on how to support patients and communities as they navigate the current, highly complex healthcare system. We also want you to engage in a conversation with our keynote speaker today. You can ask him questions over Twitter, using @CraigLipset. And use the hashtag #AHPSummit20 to engage in the conversation. And now it’s my pleasure to introduce our keynote, Mr. Craig Lipset.

Kathryn Martucci:

He is founder of Clinical Innovation Partners, which brings vision and driving action at the intersection of research, digital solutions and patient engagement. Previously, Mr. Lipset was the Head of Clinical Innovation and venture partner at Pfizer. And he currently serves as an adjunct assistant professor in health informatics at Rutgers University, as well as adjunct instructor in the Center for Health and Technology at the University of Rochester. And Craig, we are so grateful to have you here today to share your expertise and insights in this really interesting subject. So without further delay, I will turn it over to you.

Craig Lipset:

Thank you so much for that kind introduction. It’s really a pleasure to be here with you today as a part of the Voice of the Patient series. And I think that the topic we’ll be covering today around virtual clinical trials, I believe is a great embodiment of how we can listen to patients and work together to make research participation more accessible.

Craig Lipset:

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Craig Lipset:

This is just a little bit about me. As was mentioned I’m on the faculty at Rutgers in Rochester. I’m on the board for MedStar Health Research Institute and the Foundation for Sarcoidosis Research, and have a number of other affiliations along the way. Some of which lean in directly to the topic we’ll be discussing today, including serving as an advisor for the IMI in Europe on their trials at home initiative, as well as the IEEE on a global basis, supporting standards for remote trials.

Craig Lipset:

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Craig Lipset:

Okay. For the time that we have together, I’m looking forward to talking about the curve. Because this is the year 2020, and we spend a lot of time talking about where we are in the curve and flattening curves, and what happens on the other side of the curve. For this conversation, we’ll be talking about the journey of clinical trials, not just the clinical trials of COVID related therapeutics and vaccines, but the clinical trials for the rest of the medicine portfolio. And what’s happened this year in order to keep our trials running, but also some of the silver linings out of this year and what we’re seeing in terms of change coming out for how we’ll be running clinical trials post COVID.

Craig Lipset:

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Craig Lipset:

But first I’d like to share some perspective on some of the trends that were already happening for clinical trials and medicine development before January, before March and shutdowns, before the pandemic started to shut things down all around us.

Craig Lipset:

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Craig Lipset:

The two main themes for trends in a clinical trial optimization and improvement before COVID really leaned into two categories. The first is around trial digitization. And the second I’ll speak to is around patient centricity. Around trial digitization, we already had trends that leaned into our use of real-world data, diverse non-clinical trial data, whether electronic health records, wearable sensors, or wherever else that data may be sourced, and how we can use that data to generate real-world evidence. Information that can help us whether planning and designing our studies, all the way through to so much more exciting use cases, such as our ability to have synthetic control arms for our studies.

Craig Lipset:

Around the world of digital there was a great deal of momentum related to artificial intelligence and machine learning with a host of different use cases, from our ability to have predictive analytics to better execute studies, straight through to these other two categories, our ability to use mobile and different sensors together with AI to rethink our end points and enable the digitization of trial end points, rendering legacy outdated end points to become much more modern, much closer to the patient, easier to capture and more reliable. But also our ability to use AI and digital to drive process automation.

Craig Lipset:

Automation isn’t very sexy, but it can be extremely impactful and disruptive in how we are executing our studies in much more efficient ways. Here by automation, I mean our ability to take a discreet process, which today may take time and manpower, and be able to lift and replace that with different machines that are able to handle that. Whether it’s around data quality and data cleanings, straight through to how we can author and quality control our regulatory submissions.

Craig Lipset:

But right alongside all of that momentum related to digital, has been a great deal of momentum related to patient engagement and patient centricity. Some of this had been related to our strategies to improve and optimize the experience of participants in our trials, including our ability to measure their experience so that we know if our interventions are doing any good. Our ability to provide information resources for those interested in trials beforehand, for those participating in our trials to help them in their journey, but also information for patients after the trial. Thinking about deliverables that are appropriate for a participant, whether that means patient friendly versions of study results, or even enabling patients to have access to their own personal health data from the study in which they participated.

Craig Lipset:

And then finally, themes that related to access, whether that means our ability to make trials closer to home through the use of digital and other solutions we’ll be talking about, or other ways to improve access such as ride sharing and other types of travel support, all with the goal of helping to open up participation for more patients and more diverse and representative patients.

Craig Lipset:

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Craig Lipset:

Okay. Now that we’ve talked a little bit about what was happening prior to COVID, let’s shift a little bit further into the curve and talk about some of the continuity measures that started to happen as the pandemic began to shut things down.

Craig Lipset:

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Craig Lipset:

As we hit March of 2020 and we started to realize that doors were closing and people had to stay in place, there were two primary objectives that the clinical research community had as we were looking at the global portfolio of medicines that were in clinical trials. First, how do we make sure that patient safety is always being tracked and understood, and our ability to intervene when necessary? Second, how to support patients to make sure that nobody is missing doses in their clinical trial. And then third, how to make sure that we, as the research community, were avoiding missing data, and that we were able to collect the information on efficacy and safety. The reasons why we were running the study in the first place.

Craig Lipset:

There were three primary areas of intervention that really helped to pull clinical trials through this period of history. The first was our ability to shift how patients were getting the investigational product, their study drug, while they were in the trial. For some that meant rethinking and extending their supply chain to enable the supply chain to go beyond just the research pharmacy at a research site, and extend all the way to the patient in their home.

Craig Lipset:

For others it meant rethinking large molecules and how infused therapies may be delivered, very often by looking towards home health professionals and our ability to send visiting nurses into the patient’s home to support drug delivery.

Craig Lipset:

We saw radical shifts in how research sponsors, together with contract research organizations as partners, began to rethink how they were monitoring studies. Typically a process that involves sending clinical research associates out in the field to visit different investigators sites, this clearly became impractical or impossible at the start of the pandemic. And so began the adoption of different types of remote and monitoring approaches. Data-driven monitoring approaches, risk enabled monitoring approaches. And then finally, shifting location for participation. As patients weren’t able to leave the home, as sites were no longer able to open their doors to see patients, as clinical staff began to be repurposed to more urgent areas in their health systems, how did we enable the patients to stay in place, but maintain their participation by leveraging video and televisits, by shifting our end points to more contemporary ones, or by using different types of statistical and modeling driven approaches to make sure that we could fill the gap in terms of some of the data that we might wind up missing.

Craig Lipset:

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Craig Lipset:

As we look at survey data from that period of time, we see that close to eight out of 10 sponsors and their CRO partners indicated that that time in terms of the initial period of the lockdown, there was the rapid adoption of different types of virtual, decentralized research techniques. In fact, when patients were being surveyed around that same period of time, nine out of 10 patients who are participants in research indicated that things had changed in their study, with the top things that changed being identified as the use of telemedicine and other approaches to enable virtual visits to the site.

Craig Lipset:

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Craig Lipset:

So what drove all this change? Some have indicated that maybe this change means we’ve became more innovative. We suddenly began to adopt tools and approaches that were already available, but simply struggled to get meaningful adoption inside of research studies by large research organizations. In fact, these organizations have long been risk averse, and in many ways it’s actually that aversion to risk that drove the adoption, even more so than the draw and appeal of suddenly being innovative.

Craig Lipset:

The environment changed. The environment created risk in terms of the continuity and sustainability of clinical trials that were going on throughout the world. And suddenly the solutions that had been viewed as risky just a few months earlier, suddenly became the countermeasures to risk in the environment. Those same solutions suddenly became the keys for continuity. Now some may wonder, will this change last? Is this now the new normal? In fact, most of the early implementations that we saw were done using countermeasures with names like SOP waivers and protocol deviations. When we’re documenting SOP waivers and protocol deviations, it clearly implies that these are temporary countermeasures and that we’re meant to revert back to a prior way of operating. And so it raises the question, certainly at that time, is there a commitment to these areas?

Craig Lipset:

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Craig Lipset:

So let’s talk about the period, say we’ll call this at the end of the summer and into the start of the fall. Pretty close to where we are right now.

Craig Lipset:

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Craig Lipset:

When surveyed about the anticipated difficulty that sites were going to face in resuming studies that had been halted or paused, the number one concern that sites were facing was about the ability to bring patients back in. But when we look at the curve on the right, in terms of data that’s being collected by WCG, one of the largest ethics committees out there, we see trends as far as enrollment, as investigator sites, and how these really bottomed out at the start of May. But that was really our trough. And we see how of the clinical research community was able to respond and bring studies back online.

Craig Lipset:

I would say, by and large, the countermeasures that were introduced into clinical research studies during this time were successful. We did not see significant studies that had to be terminated because of the pandemic. We saw enrollment delayed, or we saw new study starts being put off, many of which are now coming back online.

Craig Lipset:

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Craig Lipset:

But as I mentioned earlier, none of this just becomes the new normal simply because it was being done for some short period of time. In fact, what we’re starting to see now is what I call the commitment to change. What we’re starting to see now are organizations that are going through the steps that they know are needed as large complex organizations, the steps that they need to do in order to make these changes the new normal. To make them sustainable. This involves relooking at their existing policies and procedures to see if any language exists that runs contrary. For example, contrary to the ability for a patient to have a visit at home. They’re relooking at their partners and their vendors to make sure that, wherever needed, they’re reopening the doors for new partners to come in and fill some of the gaps that may be required to drive this new future in their studies.

Craig Lipset:

But perhaps most importantly, they’re looking at their own training and their own culture. The training for both internal staff at a large pharmaceutical company’s development organization, but also the training at their investigator sites and the training that ultimately reaches all the way back to the patients and their caregivers who are participating in the studies. But training alone isn’t enough. We have to make sure that the culture in these organizations is embracing the change. As we know, that can ultimately be the true rate limiter to sustaining adoption of these new tools in our research studies.

Craig Lipset:

Finally, we see how organizations need to rethink their protocols. It is not enough to take a protocol that’s been written and try to bake quick changes in at the end. In fact, as I mentioned earlier, at times, our end points themselves are the rate limiters for our ability to use these new approaches. And introducing a new endpoint requires time and resources to validate a new digital instrument.

Craig Lipset:

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Craig Lipset:

Fortunately, we’re seeing this commitment being realized. One of the data points I’ll point to on the left side of your screen shows the rate of adoption of telemedicine by investigator sites. And we see how, prior to COVID, only 28% of sites indicated using telemedicine. During COVID this clearly shot up, 64%. But importantly, the forecast from the sites themselves is that 73% of them will continue to use telemedicine after the pandemic. We see this in other areas as well, such as the site’s ability to deploy remote workforce to support studies when needed. Prior to COVID, that was a small minority at 15%, but now after COVID, reaches all the way up to greater than 60% of sites. A great sign of commitment to change by the investigator sites that are required to support our studies.

Craig Lipset:

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Craig Lipset:

Now, as I mentioned, one of the primary countermeasures that kept these trials running was our ability to shift location. And this goes by a lot of different jargon. Virtual trials, sightless trials, remote or digital trials, direct-to-patient trials. For much of this conversation here, I’m going to use the term decentralized trials, if for no better reason than this is the term that the FDA used when launching a workstream at the Clinical Trials Transformation Initiative, CTTI, public private partnership with the FDA and Duke, which would produce some guidance and recommendations with best practices for decentralized trials.

Craig Lipset:

Let’s click forward. Next slide please.

Craig Lipset:

79%. When surveyed prior to the pandemic, 79% of individuals responded that home nursing visits would make participation in a trial somewhat or very appealing, indicating that there’s clearly a sense of burden and a desire for a shift in location that can help open doors. But opening doors, importantly, for diverse and representative patient populations. Because as we look at the race and ethnic differences in that particular survey, which is an important survey to the industry, done by CISCRP, the Center for the Information on the Study of Clinical Research Participation, CISCRP runs a survey every other year looking at public perceptions and insights.

Craig Lipset:

And importantly here, 85% of black respondents indicated that this shift in location was important for them. Obviously, now more than ever, there’s heightened appreciation and awareness for driving better diversity and inclusion in our studies, opening the door that these types of home-based approaches for participation are not only a good countermeasure for a pandemic, are not only important for impacting patient experience, but can also support our diversity objectives.

Craig Lipset:

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Craig Lipset:

We see these same numbers carry through when surveys were run at the start of the pandemic, or early in the pandemic, back in May. 58% of individuals indicating that they were more likely to participate in a trial with tele-health. Interestingly, these types of data are coming back on a global basis where Japanese research participants were surveyed, finding 60% would have welcomed a shift in the location away from a clinical site for participation. I call out Japan in particular, because at times we see data suggesting that shifting to, for example, home visits, may be seen as a cultural burden to some stakeholders. That say, in Japan, the concern that having nurses into the home may create extra work for the individual to get their home ready. But clearly in this case, the use of digital and telehealth solutions helps to expand and open more opportunity for patients to participate.

Craig Lipset:

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Craig Lipset:

In 2011, when I was at Pfizer, we announced the remote trial, which was the first clinical trial attempting to run entirely from the home. 2011 is when we announced it, but I began to work on the design for this study, it’s now 11 years ago. This was an opportunity that we had created to reproduce the registration trial for an approved medicine, Detrol for overactive bladder. And to repeat that study using an entirely at-home approach.

Craig Lipset:

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Craig Lipset:

We wrapped up the remote study early. We were not able to successfully complete the study because, while we were able to find many women who self identified with an overactive bladder to complete our screener and explore participation, the highly restrictive eligibility criteria for that registration study and our approach of engaging patients directly over the internet did not work to our advantage. And many of the women that we found simply did not meet the stringent eligibility criteria.

Craig Lipset:

In hindsight, had we better engaged with treating physicians in the community, we might’ve had a better chance at finding these targeted individuals. However, we were able to demonstrate a model that passed regulatory scrutiny in terms of how to enable patients to participate using telemedicine from home without ever physically seeing an investigator. A model that had never been done before and served as a catalyst for the industry.

Craig Lipset:

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Craig Lipset:

I track here the 17 year history of de-centralized trials, because even prior to that work at Pfizer, Eli Lilly had done some work with incremental use. Some visits bearing using technology. And some work with nutritional supplements at Boston University had also done the same. But as you see in this slide in the middle period, much of the energy was around that Pfizer remote study, with a lot of eyes on it to see what would happen. And what happened was what we see in the last five, six years, which is a tremendous amount of investment and creation and experimentation in this field.

Craig Lipset:

We see over the last five years just how many young companies were started, how many investors started to come into the space, whether pharmaceutical companies investing or other stakeholders in healthcare like McKesson, beginning to invest. We saw major CROs begin to create and promote capabilities in this area. And we saw a lot of experiments from large pharmaceutical companies in their portfolio.

Craig Lipset:

In the top right, we also saw the rise of a number of multi-stakeholder initiatives, bringing together different stakeholders to try to address this very topic. CITTI, the Clinical Trials Transformation Initiative I’d mentioned earlier, had a mobile trials workstream back in 2016, which included deliberate effort around decentralized trials. The IMI in Europe has their trials at home. The Digital Medicine Society is another organization. And this year alone, we’ve seen the IEEE begin work in this area around standards, as well as a new nonprofit, the Decentralized Trials and Research Alliance.

Craig Lipset:

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Craig Lipset:

Now you would’ve thought, with all of that investment in new capability being created, that everybody was doing these trials at home. But in fact, as recently as January, I stood on a stage pointing out the oversupply that we had as an industry. That our supply and demand was nowhere near in sync, given the level of investment creation and adoption and experimentation compared with how little meaningful adoption was being had in the industry. In truth, that oversupply worked to our advantage as we really came to need a lot of these capabilities this year.

Craig Lipset:

Now, how are organizations actually implementing here? We’ll take a look at the survey on the left side, and we can see that most organizations indicate that they’re implementing some virtual trial elements. Very few are saying we’re doing none. Very few are saying we’re going entirely virtual, where the patient is only from home. And in most, would refer to these as a hybrid trial, where on the one hand we have studies taking place entirely at a brick and mortar site, on the other hand, maybe there’s an instance where it could be entirely from home. But in truth, in most cases, there’s something that lies a little bit more in the middle.

Craig Lipset:

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Craig Lipset:

Okay. So let’s talk about where the puck is going.

Craig Lipset:

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Craig Lipset:

As I think about forecasts for what happens after the pandemic, there’s one baseline assumption that I hold true. And that assumption is that most everything in our lives after this pandemic will be hybrid. Before the pandemic, when it came to grocery shopping or how our kids went to school or how we took meetings or how we obtained healthcare, most of us were leaving the home for those experiences. Now we all went through a period in history where we were forced to stay home, where we needed to for the public good, and we relied more on virtual and digital tools to support us.

Craig Lipset:

As we come out of the curve, we want to get back to a grocery store. We want to send the kids back to school. But we also see that there are opportunities for us to leverage these digital tools in better ways than we ever did before. We see more and more workforces, large employers that are saying, going forward, their employees can work from home. It doesn’t mean that offices will go away, but we we’ll be more thoughtful around this future of hybrid. I think this future of people having choice in how they engage, well, I feel like I experience it every time I take the kids to Panera for dinner. I fire up an app and it lets me have a choice in that experience of having the food come to the table, being able to pull up outside and having it brought to the car, having it delivered to home. These are the types of choices many of us as consumers have gotten used to.

Craig Lipset:

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Craig Lipset:

In fact, when we look at grocery shopping, we can see that prior to the pandemic, only 3% to 4% of grocery shopping was happening online. A percentage which spiked up to as high as 15% during the pandemic. But we can start to see where this settled. The new normal is not all digital. The new normal is never going back to a grocery store. It lies somewhere in between.

Craig Lipset:

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Craig Lipset:

So let’s take that same lens and think about what I mentioned earlier, this idea of hybrid for clinical trials, where some visits may take place at a clinic and some at a site. The way the implementation is happening today is that our study protocols allow visits at the site, or they expect the visits to take place outside of the site. We put together study protocols, which will define where a particular visit will take place, In the clinic or in the home.

Craig Lipset:

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Craig Lipset:

But we can’t bring that same mindset into the way patients and consumers are interacting with the world. If Whole Foods told me that, in the month of January I had to go to the store, but in the month of February I had to have home delivery, and in the month of March I had to come back to the store, I wouldn’t call them particularly customer centric. And likewise, it’s hard to say that that model of a hybrid trial is particularly patient centric. It’s still all around the protocol, defining for where the patient can interact.

Craig Lipset:

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Craig Lipset:

And so the real future here, for me, the forecast is the next generation of hybrid trials will be trials with choice. Trials that enable the patient to participate where it makes sense for them, relative to where they are in their journey. For those of you under 40, I’ll say that’s kind of like Netflix Bandersnatch for clinical trials. And if you’re a little older, like me, I’ll call it the choose your own adventure for clinical trials.

Craig Lipset:

Now, obviously there will always be some instances where this is not feasible. There will always be instances where a biopsy is required, or we’re doing a dose escalation to a higher dose for the first time. And certainly in these types of instances, the ability to shift location will become harder, and even impractical. But we know that that’s the minority, and we know that by leveraging new types of digital tools to improve how we’re measuring, we will have more and more flexibility for patients to be able to decide where the visit makes sense for them. The kids are in for the holidays and it’s busy at home and it would be a burden to try and get across town just for a study visit, stay home. A little concerned because maybe your hand is looking a little more swollen than it did yesterday and you’d like the high touch experience of seeing your investigator, then go in.

Craig Lipset:

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Craig Lipset:

So what does this look like for research sponsors to be able to bring to life? For one, it’s a careful balance of understanding the external environment and your own internal environment. It’s knowing what types of solutions are out there in the ecosystem, looking at what competitors are doing, understanding what regulator feedback is looking like on a global basis, and understanding the environmental risk that you’re operating under for your study, whether an environment, pandemics hurricanes, or every other possible disruption that’s standing in the way of your patient getting to a site today.

Craig Lipset:

And then likewise, looking at your own internal environment, the therapeutic areas that you’re running studies in and the patient insights. The Voice of the Patient that you’re capturing to help guide you in terms of what those patients want or need in order to be able to participate in your study. Of course, looking at your geographic footprint and understanding your own culture are the additional measures that are required to figure out this pairing process. Because now what’s happening is, more and more sponsors are appreciating this opportunity to build a toolkit of these decentralized research methods electronic informed consent.

Craig Lipset:

Home health and being able to have visiting nurses or other professionals to send to the home. The ability for patients to travel to local laboratories or even local imaging centers, rather than have to travel a great distance just for a blood draw or a CAT scan. The ability to use video to engage with a patient in a remote way, and to supplement that with different types of remote monitoring technologies to be able to capture diagnostic and other data. In some cases, shifting entirely to a central investigator site model, where the patient may never go see a physical investigator because they may be located just in the cloud in a very distant space. And making sure that they have the processes and the tools in their toolkit to support drug supply for the patient, whether that means extending their supply chain so that small molecule, that pill, could get delivered to the home, or making sure that that large molecule, that infused therapy, can be administered in the home.

Craig Lipset:

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Craig Lipset:

It’s been my pleasure to share some time with you. I’m really looking forward to hearing and seeing what you have to say on Twitter. Please engage there and I will look forward to continuing the conversation. Thank you again to the Alliance for this opportunity to share.

Kathryn Martucci:

Thank you, Craig. Thank you so much for joining us today and sharing your insights. I felt like that was such a helpful framework to walk us through this topic. And we’re really excited to see all these innovations will continue to evolve and continue to assist the policy community balance high touch and high tech care for patients. So, thank you again. And for those of you listening, please join us for our remaining sessions, including our second panel discussion today at 12:00 PM. And a recording of this webinar and additional materials are available on the Alliance’s website. So thank you and have a good rest of your day.