VIRTUAL TRIALS AND COVID-19: ENSURING PATIENT SAFETY AND DATA QUALITY
Host Todd Rudo, ERT’s Deputy CMO of Cardiac Safety, is joined by Head of Patient Safety for Immunology, Hepatology, and Dermatology at Novartis, Dr. Ignacio Rodriguez. Together, they discuss clinical research in the time of COVID-19 and how the acceleration of virtual trials could be a silver lining.
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Speaking from a general safety perspective, as well as a cardiac safety perspective, what challenges have you observed in clinical trials resulting from the COVID-19 pandemic? [3:07]
I speak for myself and others, no one trained us for this and we had to quickly react. We want to ensure the safety of the participant as well as making sure the data is right. We have to consider what is in the best interest of the patient and how we can ensure that the data that is collected will be able to be analyzed at the end of the study. We had to rethink what to do, but the situation differs. For a company in Phase I with very little information, it’s not the same as a Phase IV clinical study. However, the common ground is that they try their best to maintain the integrity of the trial. In particular with cardiac safety, there are certain parts of the clinical trial where remote monitoring can continue to be done.
What approaches have you seen employed in managing these challenges? [8:40]
What I see the most is that one size does not fit all. Certain studies you cannot stop. Overall, what we have been trying to do is hold a very careful assessment of the conditions of the patients under study and the risks vs. the benefits of stopping or continuing the study.
Thinking back, what do you think was the general consensus in the industry with respect to virtual clinic trials one year ago, versus today? Was this something under discussion? If so, how was it meant to be applied, versus what are you seeing now, and versus what we may see in the future? [12:00]
One year ago virtual trials was an interesting topic that needed to be further developed and was worth discussing. Now, it is something that we jumped into in order to ensure trial integrity and safety of the patient. What do you do when you’re in the middle of a study and you realize you cannot collect that data and if you want to complete the study, changes have to be made? If you were supposed to collect the data in a certain way at a certain location, now you have to modify what you had done before in order to ensure the safety of the patient and the accuracy of the data. Virtual studies was no longer an idea, but an urgent need that had to be implemented immediately.
As we adapt to the current paradigm, certain changes are occurring in the way we all operate. There’s a lot of talk now of a hybrid model in clinical trials as a means to continue studies during this pandemic. Of these changes, what do you see as temporary, versus a change reflective of the future of safety monitoring in clinical trials? [17:48]
During these times we are getting a crash course on things like digital collection of many different outcomes and safety monitoring that in the past we were underusing or didn’t know how to properly implement. This is pushing us to better define, monitor and focus on the essentials in clinical studies. If we can make it easier for patients to be a part of clinical studies, there might be a higher participation of people that want to volunteer. If we can take advantage of the tools that we currently have available and the others that are yet to be developed, there will be more real life data.
From the patient’s perspective, do you have any thoughts as to how they might view clinical trial participation in context of the COVID-19 pandemic? [20:33]
If you can ensure patient safety and can communicate that the setting that’s been set up in a study is ensuring safety for them, that will make them feel reassured. We are making it easier for them to complete the different assessments. In order to do so, there has to be adequate training to ensure the safety of the patients and adequate data is collected.
[00:03] Dr. Ignacio Rodriguez: We are getting a crash course on things like digital and digital collection of many different outcomes and safety monitoring that in the past, I think maybe we were under using them. The beauty of that is this is really pushing us to better define the studies to monitor at least some have a major focus on the essentials.
[00:33] Intro: Welcome back to the Trial Better podcast. Today we want to shed light on clinical research in the time of COVID-19. As the world moves into a second wave of the pandemic, we want to discuss how sponsors are continuing clinical research. In this episode, we’ll discuss patient safety in the time of COVID-19, how studies are changing to ensure an even improve data quality and how the acceleration of virtual trials can be a silver lining. Leading this conversation is host, Todd Rudo and guest, Dr. Ignacio Rodriguez of Novartis. Let’s not waste time and jump into this edition of Trial Better.
[01:11] Todd Rudo: Hi everyone and welcome to the Trial Better podcast. I’m Todd Rudo, and I’ll be filling in for your normal host today Jason Eger. I’m a cardiologist by background, I’m the deputy chief medical officer for ERT based in the Philadelphia office. And today we’re going to be talking about the impact of COVID-19 on clinical trials. The global pandemic has presented unique and challenging times for pharmaceutical companies, for patients participating in studies, for sites; and today we’re going to have the opportunity to speak with a close friend of mine and colleague Dr. Ignacio Rodriguez. Dr. Rodriguez is trained in medicine and internal medicine in Bogota, Columbia and then completed his fellowship training in clinical pharmacology at Georgetown University. His emphasis in his career has been in drug induced disease and has spent almost the past 20 years working in pharmacovigilance in various pharmaceutical companies. He has experience in all phases of drug development, both with small and large molecules and is definitely considered a thought leader in the field of cardiovascular safety, which is why we’re excited to have him join us here today. He is currently working at Novartis in East Hanover, New Jersey as the head of patient safety for immunology, hepatology, and dermatology, and is an active member of the cardiac safety research consortium, currently co-chair of the CSRC executive committee. Dr. Rodriguez, thanks for joining us today.
[02:31] Dr. Ignacio Rodriguez: Thank you very much. Glad to be here and happy to talk with you about these very critical times that we are all living in.
[02:38] Todd Rudo: Wonderful. So I think what we’ll do is just kind of jumped right in and hear your thoughts about how this pandemic has been affecting the pharmaceutical industry and most specifically, what we’re going to focus on today is safety monitoring in clinical trials. So starting off there, just thinking about general safety in clinical trials and perhaps focusing on cardiac safety as well. What challenges have you observed developing in clinical trials that you’ve been a part of?
[03:06] Dr. Ignacio Rodriguez: It’s been a very, very interesting and exciting times, and this is something that I am particularly interested in and happy to be part of this because I don’t think, I think I can speak for myself and for others, nobody trained us for this and so we have had to very quickly react, in particular, looking for the safety of the patients in the clinical trials, but at the same time, also for the integrity of the data within those clinical trials to make sure that we are while continuing ensuring the safety of the participants at the same time to make sure that the data is the right one. This has made us have to rethink what to do and it’s completely different depending of the phase of development for a compounding in a phase one and with very little information on both the safety of a compound is not exactly the same thing that we have to do for a compound in a clinical trial or in a phase four clinical study. But the common ground of all of the activities that we have encountered is to ensure the well-being of a participant in these studies and try the best to maintain the integrity of the trial.
In particular, with cardiac safety perspective there are certain things that you can do in a clinical trial where remote monitoring can continue to be done without major perturbations. When you did not set up the study at the beginning with such remote monitoring, there are limitations of how we are going to start collecting ECG, for example, of blood pressure or specific monitoring, how can we ensure that the data that is collected will be able to be analysed at the end of this study and as for the individual patient safety? What we have to consider is what is in the best interest of the participant, is it to come to the clinical trial unit or is it better it to be monitored at the other location closer to where they live, where they can be attended, or if it is in our major tertiary hospital that is attending a big number of patients are on where in the world and at what time. What is really amazing is what you see at a particular time has changed almost on a weekly basis. We are seeing already searching places that recovered or are recovering and others that are just only starting to go to the peak of cases. I would also like to, from your perspective as a major cardiac CRO what have you seen?
[05:59] Todd Rudo: So I think you touched on several of the most important elements, which we’ll dig into a little bit deeper on our discussion today, but patient’s safety has to be first and foremost. The challenge is how to seamlessly continue to monitor patients in the clinical studies, not having the situation we need a halt a study or take them off medications but also protect their safety in terms of exposure to healthcare workers to other patients if they’re going to a clinical trial site where other patients are present. So technologies have existed that are now being leveraged very heavily to address the issues that you mentioned, for example, ECG monitoring, means of adapting that to be either in a scenario where a visiting nurse can go to a patient’s home and acquire an ECG or scenarios where a device can be used at home by the patient independently in order to not lose the data and to maintain safety, but also limiting exposure. Each study is different, each population is different and where the different technologies fit in best is certainly a case by case, but I think as you’re implying, I think we’ve seen very rapid evolution in the industry or adaptation in the industry to address this need. So if I could ask you just in follow up of what you discussed there, the concept of maintaining patient safety, while also protecting the integrity of the data, in recent months, have you seen any changes rolled out within clinical studies you’re participating in that have been effective, or if not, challenges that you’ve seen in trying to make these adaptations that I mentioned as needed
[07:55] Dr. Ignacio Rodriguez: Overall, what I’ve seen both within the company that I work at and what I’ve seen from other companies is that a one size does not fit all. I know that there’s some companies that have decided across the board we should stop before we continue, but there’s very simply put, there are certain studies that you cannot stop, and that is more deleterious to the patients to stop the compound in the middle of the study. Not to mention that you need to leave outside, make decisions or what to do with the patients who have already been enrolled in the middle of this study, patients that have completed those units, that’s when you still need to continue wanting to, or what to do with a patient that has to be enrolled, or if you decide to continue enrolment or not. Also to highlight that one size does not fit all, a lot will depend on what is the compound that you are talking about? Is this a compound in a critical care disease that is critical to continue or is this earlier development company in a non-critical indication in a health voluntary study, in an affected area and in that case, that decision is quite easy. Even over time, we’re seeing that you cannot even generalize say for example, country affected because we’ve seen very diverse impacts within the country and at different time frames. Overall what we have been trying to do is do a very careful assessment of the conditions of the patients on their study, the mechanism of action of the compound, the phase in development and the risks versus benefits of stopping versus continuing to study.
[09:57] Todd Rudo: Yeah, and I think what that takes us to is the concept of maybe the adaptations we need to make to our clinical trials are not necessarily, or shouldn’t be focused simply on what’s the scenario within that country or at that site at the time. But rather what are some changes we can make to just clinical trial practice in general and adapting towards probably a new future of clinical trials. So with that, let’s sort of take a step back from the pandemic issues for a moment and just talk about the concept of virtual clinical trials. As you and I have both seen in the industry, this is a topic that’s been discussed for some time now, if you think back, let’s say a year ago today, the concept of virtual clinical trials, if someone had brought up that topic with you what was your thinking about that at the time? And maybe what were you thinking in terms of a timeline as to when we may be making changes towards that? Obviously then we’ll take it and then say how that’s perhaps changed since the events of recent months. So virtual clinical trials, what comes to mind when you think about that?
[11:11] Dr. Ignacio Rodriguez: It was a very interesting topic that needs to be further developed that is worth discussing, that we could try here and there that was more or less a talk a few months back. Now it’s something that we were jumped to do in the middle of this for what we said before at the very beginning of this: to ensure trial integrity but most importantly, the safety of the patient. What I’m talking about here and I’m expanding beyond simply a virtual trial, because one might say, if it’s really a virtual trial, it needs to be assigned as such from the beginning. Here I think what you are referring is not only the design from the beginning, but what to do in the middle of a study when you realize that you have a set of desires to collect we need to identify that within the study, we have certain data that is collected, that is critical for understanding of the effects of the drug. Some are critical for understanding of the safety of the patients and there are others that are a mixture of those.
So there are some data that is very good to have, it’s important to have and it’s input that you need to have. And as such, when we are in the middle, that you realize that for many different reasons, either you cannot collect some of the date at all that if you want to continue this study and before stopping, you need to make changes into the design of the study and/or you decide that you were planning to collect the data in a certain way, in a certain location that you need to immediately for the benefit of the patient, for the safety of the patient, and to ensure that the data is accurate, you need on the spot to modify what you had done before we were thrown into the whole concept of virtual monitoring, virtual studies, flexible monitoring, in home visits, we were told that it was no longer an idea, but an urgent need to be implemented immediately.
So I have no doubt that we are living right now is going to change the paradigm of many of the things that we have been doing. I don’t think that everything is going to be 180 degrees switch now to everything virtual, but it will definitely highlight the need to add a further flexibility of what will be designing our studies, and also rethinking some of those good to have if we really need them and in case we still want them, do we really need to have them at the same level of detail as where we’re collecting other critical data on like major outcomes for efficacy or critical monitoring for safety. We could start, I would say, having different grades on the level of required evidence and I would say cleanness of the data for different levels of estimates.
[14:33] Todd Rudo: Interesting. Yeah. I mean, I think as we want to try and look for perhaps silver linings in what’s happening across the globe right now, this may be a push in a good direction with respect to that virtual clinical trial concept and just accelerating it perhaps to a different timeline than everyone had envisioned, but there are some potential advantages of these virtual time points and the concept of a hybrid model where you have clinical trials that include both clinic visits, but also home visits, utilizing different technologies. Again, the concept of silver lining, there are certain types of data that perhaps could be better collected at home rather than in the office. So thinking about blood pressure data, or heart rate trends or things like actigraphy, if we want to see how medicine may be affecting activity levels for patients. Those are our data elements that may actually become more accurate if collected remotely through virtual time points rather than in the office. So what are your thoughts there in terms of either that or maybe other potential benefits as the clinical trial space evolves to adapt to what we’re going through.
[15:56] Dr. Ignacio Rodriguez: One of the things that I see where we’re moving is that, this is a little bit of what I said before, some of the things that were discussed in the past, you know what this could be interesting to do. This would be something to explore. We are living it and we are living it because we have to. So we are getting a crash course on things like digital and digital collection of many different outcomes and safety monitoring that in the past, I think maybe we were under using them or maybe we did not know how to better incomplete implementers and we are learning on those. The beauty of that is that this is really pushing us to better define the studies to monitor at least have a major focus on the essential in the clinical study.
And also, as you were saying with virtual studies and virtual monitoring and the use of digital tools to get closer to real world experience in-home blood pressure and even from the logistical point of view, if we are able to make it easier for the patients to be part of the clinical studies, I think we might even get a higher participation of volunteers to be part of those studies and be able to collect a lot of information. We have always been saying that the clinical studies that we are conducting nowadays are in a certain way an artificial setting, that when we go after approval and we make it a completely different mode of use, maybe if we are able to take advantage of the tools that we currently have available and I’m pretty sure more that will need to be developed will allow us to have more real life data by the time of the drug is approved.
[18:03] Todd Rudo: Yeah. I think that that’s really an important point, the applicability of the data, not just the integrity of the data, but perhaps the applicability of the data to the real world may actually be improving through some of these changes we discuss. So just in our last couple minutes here, one last question to hear your thoughts. So I think it’s important we always consider the patient’s perspective and do you have any thoughts as to how patients may be viewing clinical trial participation, again, volunteers essentially, but participation in the context of this pandemic and any thoughts that you have on how we could adapt to, or even innovate to meet the concerns of patients and not be in the difficult position where we simply can’t find, volunteers to participate in our clinical studies. So thoughts, some changes we can implement to make participation more attractive to patients in the context of this pandemic.
[18:58] Dr. Ignacio Rodriguez: I would guess that this goes back to the basics. If you are able to ensure patient safety and you can clearly communicate to the patients that the setting that has been set up in this particular or a particular study is ensuring the adequate safety for them. If at the same time, we’re making it easier for them to complete all the different assessments that are required in a clinical study. I think that will make them reassured in the middle of the pandemic. There is a concern from with social isolation and they don’t want to go to the medical sites because they are going to be infected. So that is a key component and from that perspective, many companies have stopped some studies or stop recruitment of new patients because A, the patients are remaining at their houses and apartments and they don’t want to go out.
And on the other end, there are other patients that are in real need and they are more or less crying for help say, I want to be part of this study, but I want you to be able to ensure that I will be safe and that’s where I think it’s your part, going back to the previous question is the critical relevance that when we are stuck having these digital tools, it’s virtual, we all need to work together to make sure that there’s an adequate training and when I’m talking about training, is everyone, at the companies, at the clinical trial side, the investigators, the monitoring, personnel and the patient to make sure that we have very well standardized an adequate data collected from these remote visits. If we’re able to accomplish that, I think we’ll be able to ensure the safety of the patients and the adequate data collected, because if we have very poor data collected or a very diverse and variable data collected, it’s going to be very difficult to get to meaningful conclusions from that data.
[21:27] Todd Rudo: Yeah, I completely agree. Really excellent points. All right. So I think as we are out of time here, I just want to, especially say thank you, sincerely appreciate you sharing your thoughts, your insights with us today. I think these were interesting topics and certainly relevant today and hopefully useful for our audience. Again, appreciate your time and thanks so much.
[21:50] Outro: That’s a wrap special, thanks to Dr. Rodriguez and Todd Rudo for helping us understand the current state of clinical research. With the accelerated adaptation of virtual trials, we’re eager to see the next phase of clinical research and the innovation to come. Finally, please remember to comment, rate or review Trial Better on Apple podcasts or your favorite podcast channel. You can also reach us [email protected] Thanks for listening and stay safe everyone.
Dr. Ignacio Rodriquez
Dr. Ignacio Rodriguez began his work at the Javeriana University in Bogota, Columbia and trained in internal medicine. He was a visiting fellow in cardiology at Georgetown University Medical Center and completed a fellowship in clinical pharmacology at Georgetown University School of Medicine. His academic work focused on cardiovascular research and drug-induced effects in cardiac repolarization.
After holding various clinical practice and teaching positions in Columbia, Dr. Rodriguez joined Pfizer Global Research and Development in 2001. Later, he joined the Safety Risk Management Department at Roche. In 2006 Dr. Rodriguez was the Executive Committee Co-Chair at Cardiac Safety Research Consortium. His professional interests and expertise center on drug-induced disease and clinical safety, with a major focus in cardiovascular safety and drug-induced QT prolongation. Currently, Dr. Rodriguez holds the title of Head Patient Safety of Immunology, Hepatology, and Dermatology at Novartis.