Dr. Rodrigo Munhoz (Sírio Libanês Hospital, Brazil) moderates a discussion highlighting the impact that COVID-19 has had on clinical research. Featuring Drs. Nathan Pennell (Cleveland Clinic), Kathryn Mileham (Atrium Health), and patient advocate Dr. Jane Perlmutter. Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us Air Date: 9/22/2021
SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
CLIFFORD HUDIS: Hello, and welcome to the ASCO Education Podcast. In today's episode, we'll be discussing the far-reaching effects that the COVID-19 pandemic has had and continues to have in clinical research. Today, I'm excited to be joined by three authors of The American Society of Clinical Oncology's Road to Recovery Report, Learning from the COVID-19 Experience to Improve Clinical Research and Cancer Care, medical oncologist Dr. Nathan Pannell, who's a Professor of Medicine at Case Western Reserve University and Deputy Associate Director for Clinical Research at Case Comprehensive Cancer Center, Dr. Katherine Milehama, medical oncologist and Chief of Section of Thoracic Medical Oncology at Atrium Health, and patient advocate and cancer survivor, Dr. Jane Perlmutter. So the first question is, how has the COVID pandemic affected clinical research in the United States and worldwide regarding impact on ongoing clinical trials, ability to launch new trials, and ability to enroll patients into trials.
NATHAN PANNELL: Yeah, that's a really great question, and it's evolved over time as the pandemic has gone on. When things first started in early 2020, there was an immediate massive drop in enrollment to clinical trials as physicians were redeployed, nurses were redeployed to other jobs. Suddenly, all the research personnel had to start working virtually from home and didn't really have systems in place to allow them to do that. Suddenly, people could not travel to sites anymore to monitor trials or initiate trials.
And, of course, the focus for patient care really was on protecting people from being exposed to COVID. So patients suddenly were being seen as telehealth visits rather than in-person visits, and scheduled scans and other things were moved out to become less often, just to reduce their exposure. And this really, essentially, initially, stopped a lot of clinical research. So studies showed that enrollment dropped by about 40% almost immediately.
On the flip side, though, the good things that happened with this were that there was a lot of flexibility immediately taken up as the result of this. So telemedicine not only made it more convenient for patients to be seen, but it expanded the reach of being able to get to patients. Suddenly, patients could get studies done, scans and such done at local sites rather than having to drive, in my case, from West Virginia up to Cleveland.
Instead of showing up to get a bottle of pills, we could ship it to them so they could get it at home. So a lot of these flexible elements were actually boons. And so those are part of the things that we wanted to incorporate in our recommendations.
JANE PERLMUTTER: So, from a patient perspective, I think Nate has covered quite a few of the issues. To begin with, people who are very scared to come to cancer centers, and, in fact, diagnosis of new cancers went down because people were avoiding the hospital. Later on, things sort of straightened out a bit. But there's always been a challenge of getting people to enroll in clinical trials, and this added to it, the anxiety for new patients.
But as Nate pointed out, there was increased flexibility, and that really is something that patients have been and advocates have been talking about for a long time. So the use of telehealth is not universally appreciated by patients, particularly for really important visits, new diagnoses. But for more routine visits, they're very much appreciated, particularly for people who live far from the cancer center, and likewise, things like distributing drugs to their home or having some of their lab tests or scans locally. So things that we have put in our road to recovery recommendations, many of them should increase the access and availability, and therefore, diversity of patients in clinical trials and are things that advocates have been arguing for awhile. It's lovely to see that it's possible and we shouldn't go back.
KATHERINE MILEHAM: I would add to what Nate and Jane have said. The pandemic also highlighted how variable approaches are to conducting research. During the pandemic, regulators, sponsors, CROs had to implement new policies and guidance to reduce the administrative and regulatory burden and change some of those requirements. Staff positions evolved. We had people cross-covering trials and cross-covering different positions. Many tasks were completed remotely.
So, I mean, really how can we adopt what we have learned from the pandemic for future emergencies and whatever situation we may face? Certainly, we would want to continue virtual and options, maintain some of the efficiencies that we've learned. I think a word that's already been used multiple times today is flexible.
We need to be flexible in our utilization of options for site selection, study start up, signatures, maybe electronically completed, and study monitoring and adapting a more uniform system for amendments and deviations may improve our data quality ultimately and efficient use of our resources. All of these changes have impacted time, cost, and workload in clinical research, which were affected by COVID-19.
NATHAN PANNELL: I just wanted to add that in the year and a half since all of this started, a lot of the clinical research has returned very close to the level that it was before in terms of being able to open trials and enroll patients to trials. So it's not nearly as impaired as it was initially. But I will say that the flexibility has been mixed.
A lot of the regulations now have started to remove the interstate telemedicine visits, which is really starting to impact our ability to do trials. On the other hand, we're still doing mostly virtual startups and monitoring and whatnot, and a lot of them move to more electronic signatures and other things, I think, is continuing to move forward. So it's been a bit of a mixed bag in terms of how it's impacted clinical research.
CLIFFORD HUDIS: And what have been and may continue to be the downstream consequences of slowed clinical research progress and patient care.
KATHERINE MILEHAM: It's interesting when we think about the downstream consequences slowing that clinical research progress. I think there are multiple facets, some of which, as a clinician, I may not have seen. We've considered quite a bit regarding the clinical research, but also need to think about the implications of translational and basic science.
From a translational perspective, extra biopsies and blood, do we really need that or will we learn in the future that that information may have been valuable for next steps in research? We need to think about the impact of labs closing and those downstream effects. Despite grant extensions for projects, funding may have been resourced to staff retention, and that may have an impact on some of the basic science developments that will, ultimately, influence our clinical research progress on patient care years from now.
JANE PERLMUTTER: So I think Kate brings up some really important points. And I think it will be very hard to tease out the impact on basic and translational research because there are so many other factors going on. So use of liquid biopsies, which can be distributed locally, can perhaps take the place of some of the other biopsies.
From a patient's point of view, the hope is that if we keep some of the flexibility, we'll have more patients enrolling and more diverse patients. And I think we can make sure that happens, but we might not if countervailing forces return to normal. The other thing is to the extent that we are flexible and run more pragmatic trials, we might actually slow down new drug development, but we might actually improve treatment for patients.
One of my key sort of points these days is, what is the value of an efficacious drug that is not effective? And to the extent that we're running more flexible, more pragmatic trials, we'll find treatments that improve patients' lives as opposed to drugs that have minimal efficaciousness and perhaps no effectiveness, something that many patients are not aware of that distinction, but is really, I think, something we should be paying more attention to.
NATHAN PANNELL: Yeah that's a fantastic point. Fantastic point, Jane. The slowdown in some of the trials and development may be worth it if it leads to improved design of trials that make things more accessible and equitable for people to enroll in clinical trials. And I also endorse what Katie said here.
I think a lot of the-- very underappreciated how much non-clinical or clinical trial research slowed down in the last year. Doing translational research and other projects, I know at the Cleveland Clinic, our IRB was utterly overwhelmed with COVID-related research and could not even review non-clinical trial trials for much of 2020. They just refused it. They would send it right back and say, you can't-- we can't do this right now. We don't have the bandwidth for it.
And one of the other things, of course, is because clinical trials weren't designed for the pandemic and all the flexibilities that were worked into it, there were a lot of what we call protocol deviations that were happening throughout the pandemic. And a lot of work will be done now, both through ASCO and FDA, studying the impact of these deviations and how this may have impacted access to trials and the safety and validity of the results of these trials. So a lot of interesting research should be coming out of that, hopefully, in the next couple of years.
JANE PERLMUTTER: Right. And I do believe that many people are looking to do that kind of research to see the impact retrospectively. But I hope that we also devote some time to looking prospectively at to what extent some of these recommendations are actually carried forth and what impact they have on the accrual and diversity of our trials.
CLIFFORD HUDIS: And based on your experience during the pandemic, do you believe that physicians have been more hesitant to refer patients to clinical trials during the pandemic?
NATHAN PANNELL: I don't know if necessarily they're hesitant, but I will tell you that we really cannot under emphasized the pressure that's been put on our health care workforce during the pandemic and how incredibly overwhelmed everyone has become. Burnout and overwork was a major problem even before the pandemic, and it's only become worse. Many physicians, oncologists are really at their capacity in being able to take care of people.
And what we know is enrolling patients to clinical research takes time and it is really a labor of love. Most places don't get paid more for doing that, but it takes extra time. And you really-- that's one of the things that, when you run out of time in your day, that sometimes gets sacrificed, is offering someone a clinical trial. I wouldn't be surprised if overall accrual to trials went down.
The other thing that we saw is that, of course, patients have been less willing, in my opinion, to travel as far for clinical trials and are seeing their care closer to home where they don't have to travel as much. And one of the things we hope to do with the road to recovery recommendations is increase access of trials to lots more sites that are closer to patients. But as of right now, that probably is limiting access to trials.
JANE PERLMUTTER: Right. I've seen quite a bit of data on accruals, and it varies quite a bit. I think Nate has pointed out that it changed over the 18 months that we've been involved. The NCTN, the NCI cooperative group trials initially really dropped, but is pretty much back, maybe even a little bit ahead before the pandemic. Other trials, I've heard mixed results. So we'll see.
KATHERINE MILEHAM: Yeah, I think providers remain motivated to offer the best care for their patients. I think there's a challenge in lack of knowledge in which trials are open, which trials have slots available, or maybe under amendment just because of some of this backlog and need for updating some of these processes. We always want to improve care for a patient. That hasn't changed.
But to your point, we're really reevaluating how patients can participate in these trials, and maybe rather than referring them to one of your larger, top-tiered academic centers that may have a clinical trial, they may be looking for one that is closer to home. That may be a little bit different than what they would have initially but the opportunities to seek clinical trials in a regional setting rather than with as much travel, I think, is becoming a greater focus. I would also add, Nate, your point about just wellness and the need to continue to address stress and burnout for all staff members throughout this process has really come to the forefront. And I think that this has been a very unfortunate setting, allowed us to have comprehensive and open discussions about how to create a better work environment, despite all of these just overwhelming situations related to the pandemic.
CLIFFORD HUDIS: So, on the other hand, do you believe that patients have been more reluctant to enroll into clinical trials during the pandemic?
JANE PERLMUTTER: You know, I think that varies. Certainly, patients, as we said, particularly at the beginning, did not want to have to travel, so that could have limited some, and did not want to have to have extra visits where they had to go to the hospital. To the extent that the trials have been flexible and have reduced those, I think it actually could have helped, certainly, having drugs delivered to home or having home nurses do infusions. Having local scans or fewer scans could possibly be an incentive to patients. But it really varies so much from the trial, from the location, and from those curves of when COVID was up and when it was down and how we've all been adapting to it.
NATHAN PANNELL: I think that's going to be one of the most interesting questions in my mind that hopefully will come out of this is the influence of telehealth on access. I think the hope when we were first discussing and putting together our road to recovery recommendations was that expanding telehealth improved access and equity, but I've definitely heard people talk about how access to broadband and cellular services is not universal in the United States, and, certainly, there is varying limits of technological savvy, older adults not necessarily quite as comfortable with that. And I've certainly seen that myself. A lot of my patients older patients want to just do a telephone visit because they can't figure out their smartphone for Zoom. And studying the influence of this on equity and accessibility to trials, I think, will be a very interesting question.
KATHERINE MILEHAM: I think one of the things I've noticed about reluctancy in clinical trial enrollment has been in early development of agents, and patients have had some hesitancy on that drug effect on the immune system. How will this affect my immune system? Will it increase my risk for complications from COVID? Are there restrictions on COVID vaccination and my participation in this clinical trial? There have been some really wonderful questions that patients have asked in regards to their health and well-being when it comes to early investigational agents and their potential participation in clinical trials.
CLIFFORD HUDIS: in this setting, which patient populations have been most affected by lower availability of clinical trials?
NATHAN PANNELL: I think, unfortunately, the populations that were already most at risk of having less access to trials were the ones that were affected the most, so patients in lower income areas, rural. Communities that have perhaps limited access to academic sites that might offer clinical trials were probably the ones that were most impacted by the pandemic as well. Certainly, once you enroll in a clinical trial and once you've seen someone, the ability of telemedicine to help was tremendous for a lot of my patients who are from rural communities.
But initial access, probably, was significantly impacted by that. And that probably has continued, but the recommendation to increase the use and allow the use of telemedicine more routinely, things like being able to do electronic consents would, I think, greatly improve the access to clinical trials. That's one of the recommendations that we made. Continuing to allow people to get scans locally in their community hospitals and cancer centers, shipping drugs, as Jane pointed out, to patients so they don't have to drive to pick them up every month. I think a lot of things we can do will hopefully improve this access going forward.
JANE PERLMUTTER: And one thing that COVID did is it really put a spotlight on the health disparities in our country. And in some ways, I think cancer trials have been aware of this for a while and have been taking some steps to expand eligibility in a lot of ways and to provide some outreach to recruit more less represented populations. But in general, I think the United States, at least health care, is going to be paying more attention to that, and hopefully, it will ameliorate some of those issues.
CLIFFORD HUDIS: And now, moving forward to the final two topics of this fantastic discussion, ASCO recently published its Road to Recovery, Learning from the COVID-19 Experience to Improve Clinical Research and Cancer Care Report. What are the main recommendations for modifying pre-pandemic policies and practices to improve patient participation in clinical research?
JANE PERLMUTTER: Two of the recommendations from the Road to Recovery Initiative are really very much patient-focused. The first one is to ensure that clinical trials are accessible, affordable, and equitable for patients. And in the report, we outlined quite a number of steps that we've actually talked about already on this podcast that can actually have an impact on that, but they have to be implemented mindfully.
And the other goal that is very much important to patients and that we've also discussed is to design more pragmatic and efficient clinical trials that are better integrated into routine cancer care. And I think if everybody who's designing a trial thinks about each step that they're taking, whether it's eligibility or extra scans or biopsies, and thinks about how important they are and where some flexibility can be added, I think that would really help patients increase accrual. Might possibly require a slightly larger trial, but if we do trials-- if we accrue faster, that should compensate.
KATHERINE MILEHAM: Yeah, I would certainly encourage anyone listening to this podcast that has not read the Road to Recovery to take the time and really review the comprehensive approach and recommendations from the team, and then take it to that next level. In order for us to really be successful from what we've learned, we need to have an action plan and we need to then implement this into the future of the way that we conduct research, first, by implementing it into trial design. ASCO has already published one stewardship of blood and tissue biopsies. ASCO has worked diligently on broadening eligibility criteria, and has worked with Friends of Cancer Research and the FDA, and that has been quite successful and continues to expand. I think the Road to Recovery needs to have that same value and provide impact and should be a reference when writing new trials. I think that the only way we're going to see that is if we change the way that we're writing the protocols and not lose the lessons we have learned from this pandemic.
NATHAN PANNELL: One of the things that I thought was so gratifying during the process of putting together these recommendations was that every stakeholder we spoke with, whether it was the NCI, FDA, pharmaceutical industry, the contract research organizations, everyone agreed that all of these goals were positive and wanted to move towards improving access for patients to enroll in clinical research. And so I'm hopeful that as things move forward, we will continue to have the same buy-in from all of the stakeholders. Because if any of them start to resist, it's going to make it much more difficult to make the change.
CLIFFORD HUDIS: And what progress has been made in implementing roadmap recommendations? And what are the next steps?
NATHAN PANNELL: Yeah, I think it is important to point out that the roadmap really is just what it says. It's an outline of general recommendations for next steps and what can be done. But already, many of these stakeholders are moving forward to try to implement some of the changes. The FDA has been very proactive.
So during the pandemic, they were wonderful and rapidly came out with guidances that allowed a lot of the flexibilities we've already discussed earlier in this podcast, and they have continued to say that they want the trials to be patient-centric. They do not necessarily require all the nitpicky bureaucratic details that we're used to seeing in clinical trials. The NCI has put together task forces to try to address many of the same goals that we addressed in our road to recovery in trying to move things forward, and I think we can't really underestimate the power of the National Clinical Trials Network and the cooperative groups to try to implement some of these.
We have very little influence on how pharmaceutical companies will design their trials, but we do have a lot of influence on how we design NCI-sponsored cooperative group trials. And we can even-- there are steering committees that can look at and make sure that pragmatic elements and efficient elements are put into trials as we go forward. And my guess is that will be really where we'll first start to see the power of these recommendations change. And then, finally, ASCO has put together a number of task forces doing things, for example, like looking at the impact of deviations on clinical trials, on how they influence the safety and scientific validity of the studies.
CLIFFORD HUDIS: Any final comments regarding this last question, Jane? Katie?
JANE PERLMUTTER: My final comments are don't go back, but build back better.
KATHERINE MILEHAM: I would just add that the pandemic is far from over, and we will continue to learn from these experiences, and these recommendations will evolve as we move forward and continue to learn from them.
CLIFFORD HUDIS: Thank you all so much for participating in this discussion. Indeed, the burden of the pandemic has been unprecedented. Nevertheless, the capacity for resilience, collaboration, and to adapt and incorporate technology will most likely result in long-term positive lessons that may translate into improvements to clinical research for years to come. This has been a great conversation. Thank you to all our listeners for tuning into this episode of ASCO Education Podcast.
SPEAKER: Thank you for listening to this week's episode of the ASCO e-learning weekly podcast. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at e-learning.asco.org.