BY CLAUDIA GARY

Although the Office of Research and Development represents a tiny part of the VA in both budget and size—a proposed $762 million out of a total $220 billion in 2020—ORD currently funds more than 2,000 studies. Many will have a strong impact on veterans’ health care. Since it was established in 1925, the VA’s research program has focused on the needs of veterans. Even so, many developments that began with research at VA are widely used today, including the shingles vaccine, therapies for macular degeneration, the nicotine patch, improved wheelchair designs, and the first successful cardiac pacemaker.

ORD also provides many opportunities for veterans to participate in research studies that enable them to receive state-of-the-art care while helping other veterans.

When asked about funding priorities, Susan Carter, Director of the VA’s Office of Media Relations, said: “VA’s research agenda is determined through a strategic planning process that incorporates guidance and input from a broad array of stakeholders that includes scientific and medical experts in and outside VA, VA clinical leaders, veterans and veteran service organizations, and advisory groups. Specific studies undergo rigorous scientific peer review before they are funded, and investigators must show how their research will potentially help improve VA care or otherwise benefit veterans.”

According to the VA’s 2020 budget submission to Congress, the agency’s current strategic priorities include increasing veterans’ access to high-quality clinical trials, increasing the substantial real-world impact of VA research, and transforming VA data into a national resource. The proposal also notes “cross-cutting clinical priorities,” which include suicide prevention, opioid safety and risk mitigation, post-traumatic stress disorder, traumatic brain injury, and Gulf War Illness.

“In certain cases, congressional mandates or presidential executive orders dictate that funding be designated toward specific topics—for example, Gulf War Veterans’ illnesses, or deployment-related mental health,” said Carter. “Studies in these areas still undergo the same rigorous scientific review before they are funded.”

VA’s research ranges from cutting-edge science to the equally crucial development of more efficient ways to provide services to veterans, rehabilitation from war injuries, and suicide prevention. Dr. Rachel B. Ramoni, VA Chief Research and Development Officer, said the agency’s “efforts to improve the health of veterans and the nation would not be possible without the support of VA research, the research scientists, and veteran-participants.”

“The National Precision Oncology Program (NPOP) of VA is a clinical program, [although] it interacts with research efforts,” said Dr. Michael J. Kelley, Professor of Medicine at Duke University and National Program Director for Oncology at VA. “Precision oncology is DNA sequencing and [cancer] treatment directed by that testing.” Since cancer involves changes in the genes, “Next-Generation Sequencing is a reference to an advanced technique to determine the sequence of genes in tumor cells.” This information is then used to select treatments called “targeted drugs, which are mostly small molecules that can be taken by mouth. They are not chemotherapy or immunotherapy drugs.”

Although they generally do not lead to a patient’s cure, he said, “targeted therapies tend to work very well for patients who have the very specific genetic changes that we are looking for. They can cause a dramatic response. It is often the case that a cancer becomes resistant to one drug, and then we figure out another approach; that process is an ongoing effort to try new drugs that are better than the old drugs.”

Through VA, he said, “we’ve been able to offer this testing to patients who live in rural areas in particular, for example; and minorities have equal access. That is very difficult in centers that are based on academic medical centers, which are generally in more urban areas. Another thing we are able to do is rapidly integrate the new information to benefit our patients. At least several times a year there is a new targeted cancer drug. Many of the new approvals are based on this type of precision oncology work that we are doing through DNA sequencing.”

Dr. Kelley emphasized that “there is excellent cancer care available in VA, and that precision oncology is a part of that. It is accessible to any veteran being treated in the VA. If they or one of their family members have cancer, they should talk to their doctor about whether this type of testing is the right thing for them.”

Another aspect of Dr. Kelley’s work is pharmacogenomics, which is “looking to see whether there are interactions between drugs and your genes, to see if you’re metabolizing drugs differently and you might need a different dose of a particular drug or a different drug entirely. Any patient being treated in the VA for cancer can ask for this; even patients who don’t have cancer can ask for it.”

Other important work in precision oncology is being done by Subhra Mohapatra, PhD, Professor, Dept. of Molecular Medicine, Morsani College of Medicine, who is a Research Career Scientist at the James A. Haley VA Hospital in Tampa. Her work relates to new cancer immunotherapy methods for colorectal cancer. She also conducts research in the area of traumatic brain injury.

Dr. Noah S. Philip is Director of Psychiatric Neuromodulation at the VA Medical Center in Providence, R.I. “We use noninvasive brain stimulation to help people who are suffering from depression, PTSD, and otherwise,” Dr. Philip said. “On the research side, I work at the Center for Neurorestoration and Neurotechnology. We’re combining transcranial direct current stimulation with virtual reality, with a goal to help people who are suffering from PTSD.”

Dr. Philip emphasized the safety of this stimulation. “It uses the amount of electricity that you can get out of a nine-volt battery,” he said. “Essentially, what we’re doing is putting a tiny little bit of electricity into the part of the brain that helps people learn that things can be safe, and we do that while people are in the context of something that potentially is related to the PTSD—as if they’re in Iraq or Afghanistan in a Humvee.”

Asked to recall success stories, he said: “One of my guys who recently finished the study was able to see, about midway through, that the world didn’t seem so burdensome and threatening. He was able to start participating more in other areas of his life—getting a job and volunteering, and being more participatory in his romantic life with his partner. This is the sort of story we’ve seen again and again.”

“One of the reasons I do this kind of research with noninvasive brain stimulation,” said Dr. Philip, “is that I feel very strongly about the whole ‘do no harm’ tenet of medicine. And so, unlike other areas in psychiatry—unlike medications, for example—these interventions don’t cause weight gain, they don’t cause diabetes, they don’t have sexual side-effects. The other thing that I really like about it is that this gives me a way to harness what we are learning about the brain to develop new treatments.”

Dustin Tyler, PhD, is Professor of Biomedical Engineering at Case Western, Director of Engineering, Quality and Regulatory Affairs for the APT Center, and Director of the Functional Neural Interface Lab at Case Western. He also is Principal Investigator for studies at the Louis Stokes Cleveland VA Medical Center. His team is working on major changes in prosthetic devices.

“[When] somebody loses their hand or their leg, most people think about that as losing the function of the hand or the leg,” Tyler said. “But really, you’re losing everything. That’s not just the hand as it moves, but also how it senses.”

“The first thing we always ask [participants] is ‘What do you want to do? If we could replace something, what would you like it to be?’  When I started the work, I thought they would say ‘I want to do [this function or that function] with my hand.’ But with everyone that I’ve talked to so far, the first thing they say is, ‘I’d like to hold my wife’s or my kid’s hand.’”

By connecting a prosthesis directly to the nervous system, Tyler’s team has found a way to restore both sensation and function in a more natural way. “We record from a device on the prosthesis—we have a pressure sensor on the prosthesis itself—that tells us how much pressure is being applied to the fingers. We then take that [information], turn it into the language of the nerve, and apply that to the nerve. And the brain will interpret it as their hand. They feel their fingers. That’s been the really wonderful thing.”

In addition, he said, “We can also now put devices into the muscles. And that’s also a more intuitive type of control than has been available [with] bioelectrics, which basically are motorized hands. When he thinks about moving his hand, his hand moves, as opposed to flexing his wrist, so it becomes a much more natural sort of control. The same technology also applies to the lower extremities. So people can actually feel their feet touch the ground now, as opposed to not feeling anything.”

In the near future, Tyler said, “we should have a device that has a fully implanted system. Ultimately, rather than wires to the skin, it has a device in the chest that’s like a pacemaker. Both in this area and in spinal cord injury, large companies are slower to get into it, so the VA is really filling that gap and doing everything it can to move this technology to rovide a better life for veterans.”

Dr. Mark S. Bauer, Professor of Psychiatry Emeritus, Harvard Medical School, is Associate Director of the Center for Healthcare Organization and Implementation Research for the VA, a Staff Psychiatrist at the VA Boston Healthcare System, and Director of the VA’s National Bipolar TeleHealth Program. He has led development of the VA’s behavioral health team model.

“What inspired me about working at the VA way back in the early 1990s,” said Dr. Bauer, “was the ability to work in a health care system that was integrated in terms of medical and mental health services, served a predominantly impoverished or disabled population, and had a commitment to academic research and teaching. ”

His “first thought with the Vietnam generation—and I am part of that generation, although not a veteran—is that we’re all growing older and developing additional health concerns, so things get more complex than they were. So it’s likely that teamwork is going to be more important to be able to meet the needs of an aging generation.”

The team-based care developed by Dr. Bauer—called the Collaborative Chronic Care Model—is “very robust, and highly evidence-based,” he said, adding that the VA Secretary issued a press release that endorsed his findings. “This will be the model for outpatient mental health care,” he said.

Sara J. Landes, PhD, the principal investigator of “Implementing Caring Contacts for Suicide Prevention in Non-Mental Health Settings,” is Associate Director, Behavioral Health Quality Enhancement Research Initiative (QUERI) Investigator, and Psychologist, Central Arkansas Veterans Healthcare System. She said that Caring Contacts involves sending patients who have been suicidal brief, non-demanding expressions of care and concern at specified intervals over a year or more.

“Our project to implement Caring Contacts in the VA emergency department offers another way to reach out to veterans and provide suicide prevention,” said Landes. “It can help us reach veterans who may come to us in crisis but, for whatever reason, do not return for follow-up appointments. This project can help us figure out how to implement Caring Contacts in a real-world setting. This information will be helpful to VA and in non-VA settings.”

Dr. Luci K. Leykum, Professor of Medicine and Chief of the Division of General and Hospital Medicine at the University of Texas, San Antonio, was named in 2018 to head the VA’s Elizabeth Dole Center of Excellence for Veteran and Caregiver Research. The Center’s goal is to identify and implement research innovations that give veterans the choice to stay in their homes and communities with assistance from caregivers who support them.

Grant Huang, PhD, is Director for the Cooperative Studies Program, a division of ORD that specializes in the design and conduct of multisite clinical trials and large-scale epidemiological studies.

Veterans who participate in clinical trials may have the opportunity “to receive potentially state-of-the-art medications or therapies that are being tested as part of a clinical trial,” he said. “In addition, sometimes we have research called comparative effectiveness studies, which are looking at two or more of the best therapies and comparing them head to head. So in that regard, they are also getting care among what are determined to be the best options available for them in a given disease area.”

He stressed that “the studies are peer-reviewed by clinical and other scientific experts. One of the greatest things about our veterans is that they do it because they can help other veterans—and other people throughout the country as well.”

Asked how these benefits are passed along to the wider medical community, Huang said that after completion and analysis of the data, studies are often published in scientific journals. “VA is very proud to have a lot of these published in top-tier journals, like New England Journal of Medicine and Journal of the American Medical Association,” he said. “We also publish summaries on clinicaltrials.gov Within the VA, we communicate with our medical provider community to ensure that our health care providers are aware of these findings and the results.”

Huang also runs a program that helps speed up implementation of the research results. “A relatively novel approach for the VA,” he said, “is that within the Cooperative Studies Program, we start thinking about how to implement results within the VA health care community when initially planning a study. Once we have the results, we also work to identify strategic ways to implement and integrate the findings as part of the health care practice that we deliver within VA. This effort includes the experts from VA’s Quality Enhancement Research Initiative.”

Recruitment into clinical trials is a key factor that determines their success, Huang said. Although clinicians or health care providers may offer referrals, veterans and their family members also can ask about available research studies. In addition, they can go to http://clinicaltrials.gov to look for specific disease trials or locations.

Find news about the Office of Research and Development at https://www.research.va.gov, including descriptions of the broad array of research being pursued by local VAMCs, as well as academic, federal, and industry research partners. Veterans also can learn how to participate as volunteers in these studies.