Decentralized Clinical Trials Are Here to Stay

Decentralized trials are here to stay, says Dr. Isaac Rodriguez-Chavez, our podcast guests today. Hi, I'm Tom Rhoads, CEO of Spencer Health Solutions. We are delighted to have Isaac join the podcast to discuss decentralized clinical trials and why pharma companies should embrace digital technology for the benefits of patients. A former FDA officer who was instrumental in the review and approval of digital health technology in clinical trials, Dr. Rodriguez-Chavez is now the Senior Vice President for Scientific and Clinical Affairs and Head of Strategy for Decentralized Clinical Trials for Icon. I hope you enjoy this conversation with our team member, Janet Kennedy, on the People Always, Patient Sometimes podcast.

Janet Kennedy: (00:46)

I can't tell you how thrilled I am to have finally landed Isaac Rodriguez-Chavez as a guest on the People Always, Patient Sometimes podcast. He is an industry leader that is someone that everyone listens to, and it's really exciting to have him here today. He is formerly the FDA officer focusing on clinical research methodology, regulatory compliance, and medical policy development, and recently joined the private sector as the Senior Vice President of Scientific and Clinical Affairs, Head of Global Center of Excellence, DCT Strategy for PRA Health Sciences. So he's got a foot in both camps and it's going to be a very exciting conversation. Isaac, welcome to the podcast!

Isaac Rodriguez-Chavez: (01:30)

Thank you, Janet for having me and all the listeners, I am delighted to be here with all of you, sharing some thoughts on information that is really, I hope, pertinent for all of us.

Janet Kennedy: (01:43)

You have been very active as an FDA member and as a member of the PRA Health Sciences in promoting and discussing decentralized clinical trials, and it's time is now. However, for the one listener who might not realize who you are, I'd love to explore a little bit of your background, what work you did with the FDA, and then what made you decide to come over to the private sector. So can you tell me a little bit about your background and how you came to be where you are today?

Isaac Rodriguez-Chavez: (02:14)

Absolutely. I'd be happy to do so. The FDA, I was a senior officer for clinical developing medical policy and working internally. Also leading a program on decentralized clinical trials and supporting the modernization of clinical trials in general, including the implementation of digital health technologies in modern clinical investigations. The FDA is an amazing place. And my colleagues there are really wonderful, friends more than colleagues, because the work that we do really matters and impacts the entire nation. Essentially, I was a professional consulting internally and externally on decentralized clinical trials implementation of decentralized clinical trials. I believe in the modernization of clinical research. So I am a basic scientist by training with specialties in immunology and biology, but I became a clinical scientist also by training and experience over 20 plus years ago, conducting clinical trials, doing clinical research, being a sponsor, being the auditor, being essentially in multiple capacities, engage in investigations.

Isaac Rodriguez-Chavez: (03:32)

So for me, my passion is really what I discover is the direct impact on the patients and their lives, and clinical research, along with the infectious diseases, which is at the end of the generic or the bigger umbrella where my expertise lands, are the things that I like and I enjoy doing. Direct impact to patients and their lives in clinical investigations, with novel products and in infectious diseases and even in vaccines, which are also a love of my life. And that's what I did at the FDA. And then I transitioned to PRA Health Sciences to lead the strategy of a newly created global center of excellence for decentralized trials. The idea really for me was about to transition from the regulatory world and diversify into the real world in how the trials are conducted and essentially lead the strategy and implementation. We are in a transformative time in clinical research because of all of these modernization efforts that are happening building decentralized trials.

Isaac Rodriguez-Chavez: (04:43)

So I ended up believer in doing things better, and for the benefit of the patients, and PRA offered me essentially the venue to do so. So I am truly excited to be here with a group of professionals that are outstanding and they believe as strongly as I do in providing essentially end to end solutions and creating partnerships with multiple vendors, so that together and in unison, we can deliver the best in class and in the field in regarding decentralized clinical trials enabled by digital health technologies. And for the benefit of the patients and with efficiencies on the trials and the steps that can represent benefits for the sponsors, for the science - benefits for everyone engaged in the clinical investigation. This is the place, right now, as you said - now is the time, now is the place - in which everyone benefits. It's positive. There are multiple advantages for everyone, so, excited to be here. And my journey has been the one of love and passion for what I do and believing in doing things better for our people everywhere.

Janet Kennedy: (05:55)

I'm very interested in the three-legged stool of the organizations that are involved in clinical trials. You have, of course the FDA, you have the pharmaceutical company, and then you have the groups like PRA, the clinical research organizations, that really are much more involved in the implementation of the clinical trials. What I'm curious about is, is that stool steady? In other words is one leg, a lot shorter than the others? Are all three of these organizations moving forward at the same speed? Or do you find that maybe the CROs might be ahead of the game and trying to get pharma to catch up a little bit with decentralized clinical trials? Or are you finding that partnerships with pharmaceutical companies - that everybody is about at the same place?

Isaac Rodriguez-Chavez: (06:42)

I could say I see these more as a round table with multiple legs and multiple parties being engaged. One thing that is happening right now that is historically never seen is a different type of collaborations and the level of collaborations and the frequency of the collaborations between multiple entities is unprecedented. The COVID-19 pandemic really has put everyone on the discussion table to find ways to continue the traditional clinical investigations that were happening when we were hit by the pandemic. So the way to do it was the implementation of elements of decentralization. And with that, the creation of hybrid decentralized clinical trials in which some elements of decentralization are happening, and others are still happening in the brick and mortar site - the traditional clinical research site. Now days. And what we're seeing is essentially the business beyond the pandemic. The transformation that is happening really is permanent, is driven by multiple factors, and the engagement is at all levels.

Isaac Rodriguez-Chavez: (07:58)

So the industry, the regulatory agencies, the clinical research organizations, such as PRA health sciences, are really making huge efforts to work together, to drive this transformation. Of course we are in a learning curve and a learning process. All of these happened suddenly. And though we are embracing decentralized clinical trials and technologies to modernize clinical research, we're still in the transition time, we're still in the changing of how to do things. Everyone is not at the same level. Everyone's not at the same speed. There is a spectrum in terms of the uptake and implementation and racing, decentralized clinical trials and technologies; that kind of goal. Everybody's thinking about how to do it in the pharmaceutical industry, in the biopharmaceutical industry - small, mid-size, large size pharmaceutical industry - but the implementation is different. So there is a whole spectrum that can go anywhere between 20% to up to closer to 80%.

Isaac Rodriguez-Chavez: (09:08)

And the surveys show that information. But everyone is having conversations and the projections are very strong, that decentralized clinical trials really will become the mainstream of clincal research within the next two to five years. So this is happening, it is irreversible, it is transformative for everyone engaged in the clinical investigation. And the conversations are happening and the collaborative work is happening between multiple parties. So I not only see the regulatory agencies and the pharmaceutical industry and the CROs; I see the vendors, I see multiple vendors engage. I see the science engaged. I see the patient advocacy groups engaged. It's really multiple entities engaged in the conduct of these kinds of investigations. And it's for the benefit of everyone, as I said.

Janet Kennedy: (10:06)

So you're saying you really don't think we're going to go backwards to the way it always used to be done - that people have learned, not just that patients want a new way of participating in clinical trials, but this is actually a better way?

Isaac Rodriguez-Chavez: (10:21)

Pretty much. Though decentralized clinical trials are not the universal solution for every single medical product that is going to be tested, it is very common to see decentralized clinical trials in multiple therapeutic areas, and in all phases of the clinical investigation. There are multiple reasons and benefits for doing this. Essentially, the potential for enhancing convenience to the participants is a main driver for the implementation of decentralized clinical trials, the opportunity to improve recruitment and retention of participants, participants in the ecosystems where they live - meaning their homes, their towns, their cities, their countries - and not having them to fly or travel to distant places to go to a clinical research site to participate in clinical investigations is a major advantage, is a major driver. The use of technology as never before is amazing. And though technology has been utilized in traditional clinical investigations, the uptake of technology by modern clinical trial designs is very powerful, and it's happening.

Isaac Rodriguez-Chavez: (11:41)

And it's happening here to stay. The opportunity to essentially monitor participants remotely with the use of technology, the opportunity to break socioeconomic barriers and geographic barriers are very powerful. And this is all because of technology. Also, if you have technology, which is one of the elements that enable these trials, but you also make plans, proactive plans to increase diversity and inclusion, you break the geographic barriers right there. And if you optimize and you think proactively from the get-go in how to design these trials and not to retrofit a traditional trial, you have a huge potential for cost savings - something that is really appealing for the sponsors. So there is an opportunity to improve efficiencies at all levels of the modern clinical trial design, decentralized clinical trials, use technologies to enable them and maintain the quality. And the regulatory agencies, particularly the FDA, is tuned to all of this. So I think, again, this is enabled by the cities or digital health technologies are here to stay. Traditional trials, they're still exist. They will continue to exist. There will be just an increase in the use of these cities enabled by the colleges. That's what I'm saying.

Janet Kennedy: (13:10)

Sometimes I feel like people oversimplify and think of decentralized clinical trials as just the use of tele-health. And yet there is so much more in your current work, or even in what you were looking at when you were at the FDA, what kind of technologies do you think enhance a clinical trial?

Isaac Rodriguez-Chavez: (13:31)

There is not a universal answer for your question. Your question is very important, but essentially all technologies are important. And the key point in regards to the use of technology really is the adaptation that has to happen on that technology to support the specific needs of every clinical trial. And that is the point. Each technology has to be verified. It has to be validated to the end user. It has to be justified to measure, for example, the specific end points that are relevant for the clinical investigation that is being conducted. And it has to be usable. Nobody wants to have a two pounds watch on the wrist because it's going to be really difficult to wear that on a daily basis. So the technology has to be usable. It has to be user-friendly. It has to be something that everyone from the clinical staff, to the investigator, to the actual patients need to use in a meaningful way. So technology is here to enable the trials. Technology has to be adopted on a fit for purpose basis, according to the needs of the trial, the specific end points, the specific communication plans that are put in place, depending upon the nature of the disease that we're dealing with. There are many ways of dealing with technology and the bottom line really is to optimize it, to adapt it, and to make it meaningful fit for purpose technology that supports clinical trial. That's what it is.

Janet Kennedy: (15:14)

I'm very curious to hear your thoughts on the overwhelming potential for real-world data to come into play. Not that many years ago, the data from patients was sitting in the parking lot of the clinical site where they're filling out their paper diary and going, "yeah, I think I took it that day, and I think I take it that day." And now we're in a situation where not only do we know that you've taken a medication, but we also know your blood pressure or your weight or your glucometer results, things of that sort. Well, that is an overwhelming amount of data. Are the scientists that are dealing with this data, thrilled and excited to have all of this, and is it leading to a whole new level of analysis and analytic skillsets coming into clinical trials? Or do you think people really aren't prepared to know how to manage this? Because I'm thinking from a primary care physician. If I were to turn over my Fitbit data to my primary care physician, they might go, well, what do I do with this?

Isaac Rodriguez-Chavez: (16:18)

Definitely the real world data and the real world evidence are important trends that were clearly supported by our legislation. When the 21st Century Cures Act was passed in 2016. That is a different work stream and trend compared to decentralized clinical trials enabled by digital health technologies. They both have in common, the use of the real world settings to collect clinical data to assess the safety and efficacy of investigation or medical products. So in that regard, they both are really powerful. And the FDA uses real world data and real world evidence to monitor, for example, post-market safety and adverse events, and also to make regulatory decisions. And that's what they actually mentioned on the website In the real world data, real world evidence space. They also use computers and mobile devices and wearables sensors. And the idea is to gather big amounts of data - data that is related to clinical research - and that is health-related data that essentially is collected, can be collected at the clinic at the doctor's office.

Isaac Rodriguez-Chavez: (17:38)

And so this data can be adapted to allow for better designs and the conduct of clinical trials and studies. And essentially is, in addition to that, it really is a way of developing more sophisticated, new analytical capabilities. And essentially the data can be applied to resolve and do analysis of medical products in ways that were not done before. The same is with decentralized clinical trials. They are conducted in the real world setting. They are utilizing all of these technologies, and there is a need to create new ways of doing data analysis. The data analysis can be done with the use of, for example, artificial intelligence, machine learning, and new ways of doing these and ways of doing it quickly in almost real time or in any real time sometimes. For example, the capacity to see in any of these two in real world evidence trials, or in these CTs an outlier detected by artificial intelligence analytics that might represent, for example, an adverse event and if their protocol that is being monitored, there is an opportunity right there to react in more real time compared to for example, a traditional clinical trial. So yes, these are modernization of clinical research happening in the real world setting with new analytics, a lot of power in place to do things in real time or almost real time. Very powerful.

Janet Kennedy: (19:24)

What do you think are the challenges for implementing DCTs or decentralized clinical trials and DHTs?

Isaac Rodriguez-Chavez: (19:32)

I could say because we're in a transition time, though the FDA is supporting - and strongly supporting - the implementation of decentralized clinical trials and the assessment of the safety and efficacy of clinical investigations with decentralized clinical trials, and they have a history of supporting these CTs by creating a regulatory framework. That is not the same case for own regulatory agencies in the world. The EMA is in the process of understanding, for example, in Europe the EMA developed COVID-19 related guidances to enable remote activities of trials. The EMA is partnering with the Innovative Medicine Initiative, and they have implemented a center of excellence that is called "Trials at Home" to explore the use of DHTs - or digital health technologies - in decentralized clinical trials. They are developing methods to streamline data collection, as well as to essentially understand patient recruitment and retention in Europe, and use these five trials that they have put in place to inform the development of policy that is supportive of these CTs and technologies in Europe.

Isaac Rodriguez-Chavez: (20:54)

The Swedish Medical Products Agency received a grant of about 2 million Swedish, I don't remember their currency, but essentially they received a lot of money to conduct preliminary studies on decentralized clinical trials and examine the conditions and the requirements to conduct safety and efficacy studies using the CT approaches in Sweden. The Danish Medical Agency went ahead of the pack and they just issue in May of 2021, their guidance on the implementation of decentralized elements in clinical trials with medical products. And so there is a clear movement from the European regulatory agencies. In Asia, there are conversations between the regulatory agencies and multiple stakeholders to inform them on the implementation development and implementation of policies that support clinical trials. So we have a spectrum that is led by the US FDA that is really advanced in the regulatory framework that they have developed followed by Europe and the European regulatory agencies followed by the Asian regulatory agencies in the development of policies for decentralized clinical trials.

Isaac Rodriguez-Chavez: (22:20)

Meanwhile, we have to go on a country basis to understand the regulatory intelligence and the possibility of deploying multiple elements of decentralization required on each study to implement decentralized clinical trials. So a major challenge really is having the harmonization of policies, procedures, the regulatory framework, the legal framework, across multiple jurisdictions to implement the CTs globally - that it stays there. Another challenge is the digital health divide; we all know and talk about the digital health divide. And so democratizing having equal access to technology by diverse populations everywhere in the world represents a challenge. And it's also an important ethical marker. We are not supposed to include populations because of the lack of access to internet. For example, the lack of access to technology. This is something that becomes a costly enterprise because then the sponsors of the trials may need to provide that technology, that access to internet, while the participants are part of the clinical investigation. Another source of challenge is to bring your own device. For those who already have some of these devices, the use of those devices may represent sources of variability if it's not carefully looked at and controlled before deploying decentralized clinical trials. So these are some of the items that I could say represent the challenge in implementing decentralized clinical trials globally; they are surmountable if we think carefully and we plan carefully. These trials are not again, to retrofit traditional trials with a decentralized solution.

Janet Kennedy: (24:25)

Well in thinking about the process of every country having their own regulatory process, their own design; are we at all in the same place with what the data means, or do we also have to worry about the interpretation of the data coming from a decentral trial?

Isaac Rodriguez-Chavez: (24:42)

Decentralized clinical trials is all about mapping communications and mapping the data flow to have continuity on the data flow and to mitigate sources of variability. The data can be characterized and understood as coming from remote locations, coming from central locations. And we're in the process of learning right now, sources of variability, but that's one of the beauties of decentralized clinical trials - you can implement and design multiple solutions to mitigate the sources of variability of the data in these trials. And there has to be a customized statistical plan put in place to analyze the data in a meaningful way. We are yet to learn how the regulatory agencies will take all of this data and essentially what level of tolerance they may have, in regards to some level of variability that might exist in the CTs, as exist in any clinical investigation.

Janet Kennedy: (25:48)

Now that you've left the FDA and you're working in the private sector, how in your role as the Head of the Global Center of Excellence for DCT Strategy, how does that impact your ability to get conversations going, and what is your role in that?

Isaac Rodriguez-Chavez: (26:05)

My conversations are not impacted. I respect and maintain the confidentiality of the work that I did at the FDA. I essentially recuse when I need to recuse from specific conversations with specific entities or products. But other than that, I am not impacted in my daily work by leading the strategy of decentralized clinical trials at PRA Health Sciences. In fact, my level of activity is, I would say very high; I'm very engaged with multiple entities in the industry and in the clinical research field at large. And so one of the things that I do - I wear multiple hats - is to essentially assess the suitability of trials and opportunities to implement end to end solutions from the start to the very end, using decentralized clinical trials, assess technologies that can be put in place in decentralized clinical trials, partner with a great team that we have in PRA Health Sciences, including the team of operations, regulatory affairs, technology team, quality control, quality assurance, the legal team, the qualified vendors that we have to holistically assess the suitability of every opportunity that we engaged on to implement meaningful, customized high impact to end solutions on decentralized clinical trials.

Isaac Rodriguez-Chavez: (27:42)

So that is a very dynamic work. I also engage on protocol design, protocol review, protocol assessment for decentralized clinical trials, and I engage on training and education - internally and externally. I am engaged on being a spokesperson for PRA Health Sciences regarding decentralized clinical trials for the industry at large. I also provide consultation services to assess the pipelines of multiple partners and pharmaceutical companies who would like to have a holistic view of their pipeline, and leverage one clinical trial with future possibilities, and to essentially participate as a leader in the field, sharing knowledge and information regarding decentralized clinical trials technologies, the modernization of clinical research in multiple areas, including the areas of infectious diseases, vaccines, immunology, virology, oncology.

Janet Kennedy: (28:50)

Well, I have to admit, I am both proud and amazed at your workload and exhausted thinking about all the things that you do. I'm thrilled that you are over on the private side and working for a company that has an office in our area, in the Raleigh area, and I can't tell you how fascinated I am with our conversation so far. And I feel like there's a lot more that I'd love to ask you about, particularly in regards to CRAACO, the Clinical Research As A Care Option, and how patients have both factored into the changes that happen as a result of COVID and also going forward with how they're embracing decentralized clinical trials, but we're going to have to save that conversation for another day. You've been listening to People Always, Patients Sometimes, and my guests, Dr. Isaac Rodriguez-Chavez, who is the Senior Vice President of Scientific and Clinical Affairs, and also the Head of the Global Center of Excellence for DCT Strategy at PRA Health Sciences. Isaac, thank you so much for joining me here today.

Isaac Rodriguez-Chavez: (29:57)

And thank you, Janet and listeners for the opportunity to share some thoughts with all of you in regards to the modernization of clinical trials, our services at PRA Health Sciences, on the use of digital health technologies technologies in general, and the unification of clinical research with the standard healthcare systems using the CRAACO principle that we applied to. I look forward to future conversations, and please connect with me in LinkedIn if you would like to continue the conversation. Thank you again for listen.