VA Research: Putting the "D" in R&D

Increasing the real-world impact of VA research

By Craig Collins

Among thousands of studies conducted at Department of Veterans Affairs (VA) medical centers, outpatient clinics, and nursing homes every year, innovations abound. In 2006, for example, when a high percentage of military service members returning from Iraq and Afghanistan suffered from post-traumatic stress disorder (PTSD), VA mental health researchers and clinicians attacked the problem with an evidence-based intervention, cognitive-processing therapy (CPT), that VA clinical psychologist Patricia Resick, PhD, had been researching since 1988. The initiative to disseminate CPT throughout the VA brought relief not only to veterans, but to other Americans suffering from PTSD. Today, CPT is considered a leading cognitive-behavioral treatment, a frontline intervention for PTSD.

The expansive, integrated structure of the Veterans Health Administration (VHA), with more than 9 million patients treated at about 1,240 facilities, presents a unique opportunity for its more than 20,000 mental health professionals to move the work of investigators such as Resick into clinical practice. But the size and scope of the VHA can also present some challenges.

Amy Kilbourne, PhD, MPH, director of the VHA’s Quality Enhancement Research Initiative (QUERI), is a national expert in implementation science: the study of methods and strategies to promote the uptake of proven interventions into routine practice. Following on the success of the CPT initiative, she said, VA’s Health Services Research and Development Service (HSR&D) turned its focus to getting more veterans into treatment for depression – one of the most common mental health conditions facing veterans and a condition associated with greater suicide risk. In 2008, the VA estimated that about 1 in 3 veterans who visited primary care clinics had some symptoms of depression; 1 in 5 had serious symptoms that required further evaluation; and 1 in 8 had major depression requiring treatment with psychotherapy or antidepressants.

The challenge for VA clinicians wasn’t that they didn’t know how to treat these veterans, Kilbourne said – it was that its mental health experts often weren’t interacting with the veterans who needed help. “We had great programs,” she said, “but they were all in psychiatry.” In most VA facilities, mental health clinicians were “embedded” in departments distinct from the primary care settings that accounted for the majority of patient interactions. “VA saw right away that essentially confining depression treatment into a mental health specialty was not going to make a realworld impact,” said Kilbourne, “because most veterans were not going to a mental health specialist first to get depression care. They were going to their primary care doctor.”

In 2006, VA mental health researchers and clinicians treated the high numbers of Iraq and Afghanistan veterans with PTSD using cognitive-processing therapy (CPT), an evidence-based intervention that had been studied since 1988 by VA clinical psychologist Patricia Resick, PhD, and that today is considered a frontline intervention for PTSD. The wide-scale implementation and adoption of CPT for treating PTSD is the kind of translation of evidencebased VA innovations into practice that the VA is working to speed up and streamline.

In response, the VA launched an effort similar to the one that made CPT more widely available to veterans. Investigators and practitioners created and tested, through a series of rigorous studies, a model to link veterans in primary care to mental health services: The collaborative care model, in which a team of professionals – including a primary care physician, a mental health clinician, a nurse, a social worker, and other team members – helps patients deal with depression symptoms. “Then they tested techniques to improve the process by which depression treatment was occurring,” Kilbourne said, “and finally, they actually looked at the costeffectiveness of it and then tested different strategies to maintain the depression treatment in primary care programs in the VA. And then it became a nationalized program.”

The wide-scale implementation and adoption of CPT for treating PTSD, and of the collaborative care model for relieving depression symptoms, are clear victories for VA research – the aim of which, after all, is to improve the health and lives of veterans. Many VA innovations are likewise validated by research, but there’s often a lag between proving their value and actually making them valuable. An often-cited study by health informatics experts at the University of Missouri suggested that despite the growth in medical research, it takes an average of 17 years for evidence-based findings to reach clinical practice – and only about 1 in 5 proven practices ends up being used regularly in the real world. “We’re wasting a lot of research dollars,” Kilbourne said, “when we’re not able to provide to our patients all the innovations that research has found to be effective in regular routine care.”

Why does it take so long for evidence to make its way into practice? There are multiple reasons: Many investigators publish in peer-reviewed journals and get back to work, and it can take a long time for an idea to make it from the pages of a journal out into the real world, if it makes it at all. If it does, it will probably need to be adapted across different settings – which is why the VA invests in translational centers to push early adoption of innovations. “You might have a great innovation, but it might have been developed at three large VA hospitals,” Kilbourne said. “Maybe it doesn’t work in community-based outpatient clinics, because they simply don’t have the resources or the manpower to do it.” Along with this “capacity” barrier, she said, there’s also the stubborn resistance of inertia, of sticking to the way things have always been done.

CLOSING THE 17-YEAR GAP

The QUERI is an element of VHA’s HSR&D, which is just one corner of the vast research enterprise administered by the Office of Research and Development (ORD). VA research covers the continuum of medical science, from basic biomedical science to system-wide service care delivery, with the help of three other research services: Biomedical Laboratory Science Research and Development Service (BLRD), Clinical Science Research and Development Service (CSRD), and Rehabilitation Research and Development Service (RR&D). Translation into practice has always been a focus for each of these services, but VA’s 2021 budget proposal includes initiatives to accelerate the translation of VA innovations – to put them to work in the real world, faster, and maximize their benefits.

Christopher Bever, MD, who directs BLRD, is a neurologist who began his research career with the VA, studying the effects of certain drugs on multiple sclerosis in animal models. His group studied a specific immune function in a mouse model, using a molecule that has since been patented by an investigator at Emory University in Atlanta, who is developing it for use in treating stroke and, possibly, neurodegenerative diseases such as Parkinson’s.

It’s often the case that no matter how promising this kind of work – such as studying the function of cell receptors at the molecular level – the excitement can fizzle if nobody picks up the torch. The mechanism that funded Bever’s work, the Merit Award, is VA’s principal means of supporting basic preclinical biomedical and behavioral studies. A Merit Award typically supports an investigator for a period of three to four years, after which his or her discoveries may form the basis of further VA investigations that may carry it to the next stage of development. The timing of these follow-on studies, however, varies. Too often, investigators work in silos, with intense focus on their own pieces of the puzzle. It takes a number of Merit Awards – about 10 to 15 years’ worth – to produce an innovation that translates to clinical care.

Samuel Kuna, MD, VA physician and director of the Crescenz VA Sleep Center, pictured at right, discusses the benefits of the REVAMP app, which enables veterans to play a primary role in tracking sleep data and adjusting sleep habits to mitigate the effects of obstructive sleep apnea, with Army veteran Walter Broadnax at the Corporal Michael J. Crescenz VAMC. Kuna, who led the development of REVAMP, is a core investigator with the VA Center for Health Equity Research and Promotion (CHERP), and in 2012 was awarded a VA Employee Innovation Award to translate his research into practice. In August 2017, REVAMP launched as a pilot at 10 sites across the country and has since expanded to additional sites within the VA health care system.

One of the ways the VA aims to accelerate this translation and fit pieces of the bigger puzzle together is to encourage and support researchers to join forces in areas of high-priority research. In the spring of 2020, BLRD and CSRD launched a cycle of Collaborative Merit Awards to support linked studies aimed at translational activities. “The idea,” said Bever, “is getting investigators together to talk about what they are trying to do and to look at where they are trying to go with this, and then to define steps that are needed to get to, in this case, clinical trials of something in humans. And then how can we structure our Merit Awards so that maybe Chris gets a Merit Award on this part, and Dr. Smith gets one on a different part?”

The process actually began several years ago, with high-level meetings that produced research roadmaps that will lead to clinical trials in priority areas. In its first iteration, Bever said, the linked Merit Award program is strictly intramural, marshaling the expertise of VA investigators; in the intermediate term, he sees the possibility of co-funding collaborations between investigators with the VA and the National Institutes of Health (NIH).

Merit Awards are based on hypotheses posed and pursued by investigators. But before a drug or treatment can be cleared for clinical trials, Bever explained, it has to clear several hurdles for approval by the U.S. Food and Drug Administration (FDA): “You have to show that the drug doesn’t have some undesirable toxicity. You have to show that it doesn’t cause cancer, and you have to show that it doesn’t cause fetal malformation. And then you have to characterize how it behaves in the body. You can pay people to do those things. But they are not hypothesis-driven.” Another new BLRD/CSRD funding mechanism, for drug and biologic development, is designed to clear these regulatory requirements and support preclinical studies that will move a drug or treatment toward clinical trials. So far, about a half-dozen of these have been awarded to accelerate the translation of VA innovations.

A clinical trial, of course, isn’t the ultimate goal of VA research – it’s implementing a drug or treatment that has proven successful in those clinical trials. The VA’s large-scale, multicenter trials are coordinated by ORD’s Cooperative Studies Program (CSP), which until recently had no formal mechanism for moving proven drugs or treatments into VA health care. “We would develop a study,” said CSP Director Grant Huang, MD, “and we would tell people about it, and hopefully they would say: ‘Yeah, that’s a great idea. Let me do something with that.’”

A recently launched initiative, the CSP Implementation Program, loops in VA’s implementation experts at the beginning of the trial design process, before a study is launched. The new process, Huang said, is a way of not only weighing all the standard concerns involved in trial design, but also “starting to think about the implementation requirements up front, and then building that into the design of the study so that when the results are available, they are useable in a way that then can be more readily deployed in the health care system.”

THE VA’s IMPLEMENTATION SCIENTISTS: RESEARCH MEETS THE WORLD

Meanwhile, Kilbourne and the VA’s implementation experts continue to explore new ways of moving the VA’s evidence-based discoveries into the mainstream of clinical care. HSR&D alone funds 18 distinct Centers of Innovation (COINs) around the country, each dedicated to ensuring a particular area of research has the greatest possible impact on VA health care practices and health outcomes for veterans.

VA implementation scientists hope to build on these efforts. ORD’s recent budget proposal recommends new Translational Science Initiatives, such as the efforts that broke CPT and the collaborative care model out of their silos and made them standards of VA mental health care. “A lot of our innovations haven’t really been tested in broad populations,” Kilbourne said. Implementing the Translational Science Initiatives, she said, will compel investigators, early in the validation process, to move their innovations beyond smaller, more controlled settings – “and maybe do some further testing and validation of these innovations in a broader population. And that could include going out to smaller VA facilities or community-based outpatient clinics. We want to make sure that frontline providers feel comfortable in using the new innovation, and ensure that it’s actually effective [in a variety of settings].”

These proposed initiatives will work in tandem with HSR&D’s Implementation Research Initiatives: multicenter studies of implementation strategies for moving innovations into practice. These studies focus on one intervention, randomized at different VA sites whose providers receive either standard implementation training or training along with facilitation services. “You need about 40 or 50 sites to do a study like this,” said Kilbourne, “to really understand if the added facilitators make a difference in helping frontline providers use that intervention properly.”

Dr. Sara Landes, a psychologist at the Central Arkansas Veterans Healthcare System, is leading a study evaluating the implementation of REACH VET, a program aimed at increasing suicide prevention outreach for veterans at highest risk for suicide, at 28 VA medical centers. The study will make it possible to identify and address potential barriers to implementation so the program can run as smoothly as possible.

As Kilbourne points out, VA’s frontline providers are often the best judges of what will work and what won’t in a particular setting – but they often don’t have the tools they need to succeed. Sometimes this is due to a lack of familiarity with the basics of implementation science, of how to introduce new practices to an existing system. The QUERI recently established the VA’s first fixed training programs in implementation, coordinated by its Center for Evaluation and Implementation Resources (CEIR). There are currently six of these Implementation Strategy Training Hubs, two in California and one each in Michigan, Massachusetts, Texas, and Arkansas. “We want to be able to support providers who want to use the innovations, but who may need additional guidance, training, or resources to use that innovation,” Kilbourne said.

One area of implementation research that Kilbourne is particularly excited about, she said, is the domain of “usercentered design,” such as the investigation conducted in the mid-1990s by entrepreneur Jeff Hawkins, who had an idea for a personal digital assistant (PDA), but wanted to spend time imagining how it would be used before he built an expensive prototype. Hawkins carved a block of wood and carried it around in his pocket for several weeks, pretending it was a working device, in order to get insights into how he would use it. If somebody asked to set up a meeting, for example, he’d pretend to schedule it on his block of wood. The resulting PalmPilot became a digital repository for addresses, calendars, memos, and to-do lists.

A similar process – getting patients and providers in a room together to talk about an innovation and how it might be adapted to fit their needs and priorities – is often used in the design of prosthetics, and Kilbourne would like to see it applied to other innovations as a way to prevent early missteps. “You want to start with an intervention that is halfbaked, and seems like a promising intervention,” she said, “coming from a translational scientist, someone who is just really tinkering with things still, and then you give it to patients and providers and let them design it for you. That’s a new and cutting-edge area in implementation science.”

The VA has long been on the cutting edge of medical science – and through its host of new translation initiatives, it aims to push more of these groundbreaking discoveries into everyday care. “We’re probably one of the few federal agencies that has really prioritized the need to implement innovations into routine practice,” said Kilbourne, “and the need ... to decrease that 17-year gap between research and practice. I think in many respects the VA is at the forefront of doing that.”