Besides being the biggest health care delivery organization in the country, the Veterans Health Administration is also one of the biggest medical research organizations. For how it goes about the business of research involving human subjects, Federal Drive with Tom Temin turned to the director of the Office of Research Protections, policy and education, Dr. Molly Klote.
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Tom Temin: Dr. Klote, good to have you on?
Molly Klote: Well, thanks for having me on, Tom. I’m excited to talk about VA research.
Tom Temin: And VA research involves many different modes of research. And I guess you’re most concerned with those that involve human subjects. And what are the priority areas right now that you’re looking at with respect to the type of research that requires people to be involved?
Molly Klote: So we have a whole series of strategic priorities, two that stand out, in my mind, look at increasing our veterans access to high quality clinical trials, and then putting our VA data to work for veterans. But when you talk about the specific medical research priorities, we have a few that cut across a number of medical specialties. And those include traumatic brain injury, PTSD, suicide prevention, we have pain studies, studies on opioid use. But then specifically for veterans themselves, we’re focused on military exposures like Gulf War illness. But in addition to that, we’re doing research in the areas of precision medicine, most prominently right now in precision oncology. But just to be clear, not all human research is about clinical trials. Some of our clinical trials – and as I alluded to in our priorities – is about leveraging data. And so we have large data sets within VA. And we leverage those for studies, to look at outcomes and risks. And we look at genomic data that’s been provided by veteran volunteers in programs like the Million Veteran Program. We’ve got more than 830,000 veteran volunteers in that research study. And we’re always looking to increase diversity with women and minority veterans into that study. But we also then have studies of – you know, there are surveys, there’s interviews or focus groups, those types of studies that go on with human subjects.
Tom Temin: So in other words, just to make an example, in the area of PTSD, you could get data on a large set of people that have PTSD. And by looking at the circumstances under which their injury occurred, what happened afterwards, their background, their activities – you can get a picture based on that sort of data without actually having them subject to a trial or a medicine test. Is that a good way to put it?
Molly Klote: That’s absolutely right. And sometimes we use the data that we have within the medical records to then design therapeutic-type trials or other interventions that might help people with PTSD.
Tom Temin: So that the data could lead you to then conduct a study or a clinical trial-type person, and then you would get volunteers to go ahead and sign up?
Molly Klote: Absolutely.
Tom Temin: And I noticed protections are part of your title: Research Protections, Policy and Education. I guess there’s quite a number of protocols that have to be followed for people to be involved in research?
Molly Klote: Absolutely. The VA is one of the signatories to the common rule, which is the federal regulation on how to conduct studies within the United States. So we adhere to all of those rules, we also adhere to all the FDA regulations regarding human research, and Protections really comes down to making sure the study is ethical to conduct in humans, and making sure that it’s scientifically designed in a way that the question is answerable and that, you know, putting people at any kind of risk is actually worth the time and effort that’s going into the study for those volunteers. But the clinical trials themselves are highly regulated. And especially if you’re doing an intervention, like giving a drug or other kind of treatment in those, there’s a whole slew of review processes that get involved when you do this. We have a very rigorous scientific peer review process. And then there’s reviews by safety committees, there’s all sorts of committees that get involved. And then ultimately, what’s called an institutional review board, which is the ethical review board. And that board then has responsibilities for ongoing oversight of the study as long as it’s going on. So if there are adverse events, if there are things that need to be changed in the study, and at times the subjects of the study, the participants in the study need to be re-consented that the information we learned during the course of the study is significant enough to change the conditions of the study. And we go back to the participants and let them know that information through an informed consent process. And just to back up a second, before anybody gets into a clinical trial, they go through an informed consent process. And it’s where they’re fully informed of any of the potential risks and all of their rights, including the option to stop their participation at any time. And all research involving humans within VA is voluntary. We also have all of our clinical trials registered at the national database of all clinical trials at ClinicalTrials.gov. So we’re pretty transparent about what we’re doing within VA. And also at VA, we have a separate office, from my office, called the Office of Research Oversight. And being independent, their whole job is to help ensure the protection of our subjects in our studies by making sure that the investigators are adhering to what was approved by the institutional review board.
Tom Temin: We’re speaking with Dr. Molly Klote, she’s director of the Office of Research Protections, Policy and Education at the Veterans Health Administration. And looking back on trials and studies and data accesses, and so forth over the years, this is something that VHA has been doing for quite a long time. What are some of the breakthroughs, or some of the contributions to medical science that have come from VA research?
Molly Klote: That’s one of the great things about being here at VA, because VA has such a long and proud history of contributing many, many advances in medical science and the most notable ones and the ones – hopefully your listeners have heard about – the approval of the shingles vaccine. We had a big part in that. We’ve played a big role in prolonged exposure therapy and telehealth and treating PTSD. We were actually involved in documenting the value of daily aspirin therapy in the prevention of heart attacks and strokes. We have participated in a number of studies regarding blood pressure control. We looked at cardiac bypass surgery, deep brain stimulation for Parkinson’s, we helped in the development of the cardiac pacemaker, the nicotine patch, managing tinnitus for people with ringing in their ears, and we played a large role in prosthetics. So the LUKE arm or the Empower foot prosthetic – again, lots and lots of studies, I could rattle off.
Tom Temin: Yeah, they go way beyond veterans, because I think you hit two or three of my own personal hot buttons, there, in that list of issues. And I was just wondering, in recent months, has the VA participated in any research connected to the pandemic or to COVID?
Molly Klote: Yeah, well, how long do you have? We have really taken a large role. And as you said in the introduction, we are the largest integrated healthcare system in the US. And we’ve got more than 100 research programs embedded in our medical centers all across the country. So at the start of the pandemic, we were in this really unique position to turn much of our research towards the COVID problem. And since March of 2020, VA also funds intramural projects, meaning projects by our staff to do research. And we’ve funded over 135 unique projects, or we modified an existing project that was going on to turn its attention toward COVID. We also partnered with NIH and a number of pharmaceutical companies. And today we’ve got more than 70 of our VA medical centers involved in COVID studies. And these include clinical trials, they include therapeutics, we’re again doing analyses of large data sets, looking for risk factors and outcomes. We’ve got a number of biomedical laboratory studies, which is sort of the basic research that you think about of people in laboratories, we’ve participated in 3d printing of personal protective equipment. And we do that in conjunction with NIH and FDA and America Makes. We created a volunteer registry, so in order to get the word out and get people motivated to join some studies, we created a volunteer registry and 56,000 people signed up, the majority of those were veterans, and about 23% non-white, which is really important because promoting participation among diverse groups, and especially in our communities of color, who have been the hardest hit by the pandemic has been a big focus of VA, to try to ensure that the therapeutics and vaccines that are being developed are going to work in those communities of color. But most prominently, we were a partner in the federal COVID-19 response known as Operation Warp Speed, and 26 of our medical centers participated in the COVID-19 vaccine trials. And we enrolled more than 1,500 veterans to date in those studies. But we’re also participating in what’s known as the active trials, which is an acronym for accelerating COVID-19 therapeutic interventions and vaccines. And that’s a series of inpatient and outpatient trials. And we’ve got about 30 of our centers working on that. But then we started our own project. So VA CURES – another acronym – is working on enrolling 700 veterans, looking at the effects of COVID convalescent plasma. So that’s the blood product that you give to someone who’s infected. It contains the antibodies against the virus and hopefully will shorten somebody’s course of COVID-19. But we’ve also established a large bio repository. It’s a biobank, it collects and stores and manages specimens so that we can do further bench laboratory research and other research on that. We’ve got partnerships with the Department of Defense and 90 of our VA medical centers took part in the Mayo Clinic’s big expanded access protocol for convalescent plasma back at the start of the pandemic.
Tom Temin: All right, you said, “Do I have time?” You certainly had an excellent list there. And let me ask you this in the COVID research areas, as well as any of the other that we discussed, the research that’s been ongoing before the pandemic, how do you avoid duplication of effort with NIH and other federal entities and other academic entities that might be doing similar work, so that everybody spends their resources the most efficiently?
Molly Klote: So for the COVID studies, it was COVID federal response Operation Warp Speed that coordinated much of that. But for other types of research that we do, we are part of the National Research Action Plan for the mental health study. So for TBI, suicide, post-traumatic stress, we work with the other federal agencies to ensure that we coordinate our efforts. For cancer trials in particular, we coordinate with the National Cancer Institute at NIH, through a partnership called NAVIGATE. We also work with the National Institute On Aging. As you know, we have a large percentage of older veterans in our population. And so our partnership with NIH is really important in ensuring that we’re covering those needs of our veterans.
Tom Temin: And we should point out too, that you had a long career as a medical practitioner or a physician in the army. Before joining Veterans Affairs, tell us how that’s informed the work you’re doing now.
Molly Klote: So I was very fortunate to be trained as a doctor. I went to school at the Uniformed Services University in Bethesda, Maryland, and trained at Walter Reed. I did my fellowship in allergy immunology at Walter Reed, and was very fortunate to get to both practice and do some clinical research. For me, though, and how I ended up in the job I’m in now is, as a researcher, I got frustrated with the regulatory processes of getting research and through all those hurdles that I talked about earlier in the interview here. And there was an opening in the research office, and my clinic chief at Walter Reed at the time allowed me to apply into that job. And that really started me on a trajectory of working on process improvement and learning all the regulations, so that I could help other researchers get their work done. And ultimately, within the Army, I ended up overseeing all human subjects, or all Human Research Protections, all the policy for that, and compliance for the Army Surgeon General. And honestly, at the time I finished in the Army, I thought it was at the top of the human research pyramid. I had no idea of the scope of the VA mission. And so as a veteran, I’m very proud to come over to VA and get to use all that I’ve learned at DoD to help shape smart and effective policies and processes to help the dedicated researchers and staff here at VA be able to accomplish their mission in research. We’re implementing strategic infrastructure right now to be a more effective integrated, essentially enterprise platform for research for the nation. Because we do aspire to be America’s learning health care system.
Tom Temin: And we tend to look back at the last pandemic of the early 20th Century, and marvel at how much medicine has changed in that century. But in your career, in 30, 35 years, medicine has changed dramatically, even in our own lifetimes, hasn’t it?
Molly Klote: Absolutely. There’s no question. I mean, the emerging infectious diseases that we’ve seen around the world, our ability, especially in allergy immunology, to assess the immune system, and to figure out how it works – it’s one of the most complicated systems in the body. And we continue to learn and what I love about research is that it never lets an opportunity pass to study and to make progress in our understanding.
Tom Temin: Dr. Molly Klote is director of the Office of Research Protections, Policy and Education at the Veterans Health Administration. Thanks so much for joining me.
Molly Klote: Thanks a lot, Tom. Appreciate it.
Tom Temin: And she’s one of several people we’ve been interviewing as VHA marks 75 years as an agency. We’ll post this interview and all of them at FederalNewsNetwork.com/FederalDrive. Subscribe to the Federal Drive at Apple Podcasts or wherever you get your shows.