Summary Minutes - May 1-2, 2017

National Advisory Board on Medical Rehabilitation Research (NABMRR)
National Center for Medical Rehabilitation Research (NCMRR)
Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD)
May 1-2, 2017

Introductions

The 54th meeting of the NABMRR was called to order at 9:00 a.m. Board members introduced themselves, followed by brief introductions from NIH staff and other visitors. Minutes from the previous meeting of December 5-6, 2017, were unanimously approved. Future Board meetings will be December 4-5, 2017, May 7-8, 2018, and December 3-4, 2018.

Members Present:

Amy Bastian
Michelle Camicia
Sureyya Dikmen
Richard Ellenson
Kathleen Friel

Allen Heinemann
Gregory Hicks
Joseph Hidler
Kenton Kaufman
Indira Lanig

Dennis Matthews
Kevin Means
Randy Nudo
Kenneth Ottenbacher
Richard Shields

Members Absent:

Anthony Delitto

Gerald Francisco

Fay Horak

Ex-Officio Members Present:

James Anderson, DPCPSI
Diana Bianchi, NICHD
Teresa Brininger, DOD
Alison Cernich, NICHD
Patricia Dorn, VA
Michelle Grimm, NSF
Lyn Jakeman, NINDS
Lyndon Joseph, NIA
Mary Lovley, RSA/OSERS
Ralph Nitkin, NICHD
Lana Shekim, NIDCD
Chuck Washabaugh, NIAMS

Ex-Officio Members Absent:

Jerome Fleg, NHLBI
Kristi Hill, NIDILR

NICHD Staff and Visitors:

Joe Bonner, NICHD
Leif Brierley, PPSV
Tim Brindle, VA
Scott Campbell, AOTF
Theresa Cruz, NICHD
Diane Damiano, CC-RMD
Robyn Ellerbe, APTA  
Tinera Fobbs, NICHD
Jennifer Jackson, NICHD
Scott Janis, NINDS
Rusti Johnson, NICHD
Lisa Kaeser, NICHD     
M.J. Karimi, NICHD
Naomi Kleitman, Neilsen Fn  
Jim Koenig, NINDS
Audrey Kusiak, VA
Susan Lin, Mass Gen Hosp
Cora MacPherson, Soc & Sci Sys
Sue Marden, NICHD
Wendy Nilsen, NSF

Georgina Peacock, CDC
Grace Peng, NIBIB
Louis Quatrano, NICHD
Karen Siegel, VA
Meredith Temple-O’Connor
Biao Tian, CSR
Lois Tully, NINR
Cheri Wiggs, NEI

NICHD Director's Report

Dr. Diana Bianchi explained that her plans for NICHD have evolved as her understanding of the institute has expanded, but the core values remain the same. To promote transparency, Dr. Bianchi sought to identify barriers to funding and improve the utility of the NICHD website. She noted that she was in the process of meeting with representatives of all the branches of the NICHD, which include 950 intramural and extramural employees. Then Dr. Bianchi would summarize her observations and determine a path forward. She noted that the NICHD last developed a strategic plan in 2000 and that she took part in the NICHD visioning effort in 2010.

In fiscal year 2016, NICHD received $1.338 billion, most of which went to extramural projects; she added that  any budget cuts were likely to have significant downstream effects. She indicated that a portion of every NIH institute’s budget is “tapped” to support trans-NIH initiatives, such as the Clinical Center. A small portion of the institute budget went to administrative management in the form of research management and support (RMS). In fiscal year 2016, 3.4% of the NICHD’s funding went to RMS, which was modest and in line with other NIH institutes and centers (ICs). Dr. Bianchi emphasized that every year, about one-half of the NICHD’s funding was committed to ongoing research project grants (RPGs). She announced that Congress had only recently passed a budget for fiscal year 2017, which would end September 30.

The President’s proposed budget for fiscal year 2018 included a $5.8 billion cut to NIH, a reorganization of NIH ICs, and other changes.

Dr. Bianchi described her broad vision for NICHD, giving some details on each of the components. First, she discussed the need to better define the NICHD “brand.” She felt that NICHD should better communicate its focus and vision with a more user-friendly website and better messaging. Because of its name, the NICHD was perceived, even by some researchers in the field, as supporting primarily pediatric research. Once the NICHD defined its brand, she explained that it must find ways to communicate the brand succinctly and clearly, particularly through the website. Because mobile devices are so commonly used (across all socioeconomic categories), the website would be optimized for mobile devices. The website would also be more attractive, more engaging, and more useful, and would better highlight research supported by NICHD.

Dr. Bianchi also discussed the need to listen to the voice of the patient. To better incorporate the voices of patients into the work of NICHD and put a human face on its research, Dr. Bianchi suggested following the model of the National Center for Advancing Translational Studies (NCATS), which relied on patient advisory groups to help build the Rare Diseases Clinical Research Network.

Dr. Bianchi described building bridges across the NIH and with other organizations. NICHD was heavily involved in NIH’s All of Us Research Program℠, formerly known as the Precision Medicine Initiative®. The study planning board, which includes NCMRR Director Dr. Alison Cernich, ensured that appropriate populations were included in the program. NICHD was working to ensure that the plan adequately addressed children through the addition of a pediatrician on the study’s planning committee. Along the same lines, Dr. Bianchi stressed the importance of integrating pediatric and obstetric research and care—for example, by linking clinical networks for maternal–fetal medicine and neonatal care. NICHD was also exploring collaborations with the National Human Genome Research Institute and was heavily involved in an NIH partnership with the Bill and Melinda Gates Foundation that focused on women’s health, children’s health, and HIV/AIDS, among other topics.

Dr. Bianchi highlighted the need to catalyze innovation and translating research into practice. She pointed out that many clinicians are now screening pregnant women for genetic disorders using simple, noninvasive, blood-based DNA tests, leading to a significant decrease in use of more invasive, riskier procedures. She added that this change occurred in only 5 years, primarily fueled by industry. The example showed that transformation was possible, although she recognized the need to balance the efforts of government, academia, and industry.

In the training domain, Dr. Bianchi raised the need to identify scholars most likely to succeed. Dr. Bianchi stressed that the NICHD had consistently dedicated 5% to 7% of its extramural dollars to training and remained committed to maintaining that level of support. However, the NICHD actually gave more money to institutional career development programs than to individual career development awards. But preliminary analysis indicated that those who apply for individual career development awards were more likely to succeed in the long term (i.e., successfully compete for an NIH grant and serve as principal investigator). NICHD would be looking at predictors of persistence and success to invest resources accordingly.

Dr. Bianchi discussed the need to prioritize data science and sharing to leverage investments. She described the NICHD Data and Specimen Hub (DASH) and the Placental Atlas Tool as two examples of shared resources that not only facilitated research across sites but also provided opportunities for training and early career development. The DASH tool is available online at http://dash.nichd.nih.gov.

And, finally, Dr. Bianchi emphasized the “A” in “advisory council.” NICHD sought input from the NABMRR and hoped Board members would continue to weigh in on funding priorities, training (especially for physician–scientists), and potential new strategic partnerships.

There was brief discussion about data supporting the new DNA blood tests for pregnant women. A Board member asked why there were concerns about the pipeline of physician-scientists. Dr. Bianchi explained that the data indicate fewer physicians were applying for NIH research grants and that they had a lower success rate, and yet they brought unique perspectives to the table. A Board member suggested that strategic planning was geared toward the known, while scenario planning was a more flexible mechanism for preparing for an unknown future. Dr. Bianchi said she perceived scenario planning as an approach to day-to-day operations, while strategic planning helped set long-term priorities. She added that, thanks to a recent effort to tighten its referral guidelines, NICHD should ensure that more of its funding goes to the institute’s priorities.

A Board member asked about the role of public–private partnerships in Dr. Bianchi’s vision for NICHD. She indicated that the institute had engaged in some partnerships in the past, but she recognized the need to adapt to a fast-changing world. She acknowledged that technology and science could move faster with support from industry. A Board member stated that the Small Business Innovation Research (SBIR) and Small Business Technology Transfer Research (STTR) grants moved too slowly and were out of sync with private funders. Dr. Bianchi said such programs could be evaluated. She added that she and Dr. Collins supported public–private partnerships. An audience member pointed out that the Foundation for the NIH had resources and capacity to act as an intermediary between private industry and NIH ICs. Another audience member said pediatric spinal injury was orphaned within the rehabilitation research community but fit well with NICHD’s focus on pediatric health and rehabilitation in general. It was noted that there was strong advocacy around research for pediatric genetic disorders, but traumatic disorders were underrepresented.

NIH Research Plan on Rehabilitation Annual Report

Dr. Cernich explained that as part of the research plan, she and Jennifer Jackson, Ph.D., evaluated and coded numerous extramural projects that were funded by NICHD and defined within the NIH Research, Condition, and Disease Categorization” (RCDC) System. She cautioned that the initial effort was a limited, preliminary step, and that projects came from the 2015 NIH portfolio.

Each project was categorized in two tiers: First, projects were assigned a primary and secondary code based on the primary and secondary aims proposed: A) rehabilitation across the lifespan; B) community and family; C) technology use and development; D) research design and methodology; E) translational science; and F) research capacity and infrastructure. Projects were the further coded in a second tier with respect to whether they were: basic research; disease-related basic research; or applied research (translational or clinical).

Dr. Jackson described the coding process and gave some specific examples. One immediate finding was the lack of projects categorized as B: community and family. The most common combination of primary and secondary codes was of A, rehabilitation across the lifespan, and D, research design and methodology. Dr. Cernich said that while this initial analysis revealed some gaps, a much more comprehensive analysis involving research applications assigned to other ICs would provide further insights. She emphasized that analysis is needed to inform the NIH research plan. In response to a Board member question, Dr. Cernich clarified that, with approval from the trans-NIH rehabilitation committee, additional categories could be added as needed.

A large proportion of the projects were categorized as F, research capacity and infrastructure, which required a different analytic approach. (A later presentation at this meeting addressed the Medical Rehabilitation Research Infrastructure Network, and data on how infrastructure grants contributed to training would be provided to the Board at its December 2017 meeting.) At the December meeting, the Board would be asked to form a subcommittee to assess the current model for training in rehabilitation and propose a strategy to develop training opportunities and partnerships. The annual report would include a list of funding opportunity announcements (FOAs) that involve rehabilitation. Other issues for analysis were methods to encourage knowledge translation (to ensure clinical impact), interdisciplinary collaboration, and recruitment of individuals with disabilities into the field; the Board would form an additional subcommittee for that in December as well.

Regarding training, the NICHD was conducting a broad review of training programs and approaches. The analysis of training for the NIH rehabilitation research plan was on hold until December to give more time for coordination with a broader NICHD discussion. And the NABMRR subcommittee on training would have a liaison who also serves on the broader NICHD advisory group. Dr. Cernich would also discuss these issues with the National Science Foundation (NSF) and other organizations that promote science, technology, engineering, and mathematics research.

The NIH rehabilitation listserv, which the NCMRR oversees, continued to highlight FOAs in the area of medical rehabilitation. The listserv also incorporated information from other agencies, such as the NSF and the Department of Defense (DoD). Analysis of the types and themes of FOAs was underway.

Dr. Cernich explained that the internal NIH application iTrans tracked projects throughout their lifespan, identifying their clinical impact following publication. She used iTrans to look at projects in the 2015 NIH rehabilitation portfolio. Notably, 27% of the more than 20,000 publications found by iTrans had been cited in clinical guidelines, which was higher than the median for NIH publications from other domains. Looking at projects from 1994 to 2015, iTrans showed a growing impact of rehabilitation research on human clinical practice guidelines.

Working with the Office of Portfolio Analysis to better understand whom NICHD funds, Drs. Cernich and Jackson assessed investigator biosketches for about 1,200 rehabilitation grant applications across NIH. The effort identified the main specialties of investigators applying for physical rehabilitation grants. Physicians, psychologists, and bioengineers were the most heavily represented, while physical, occupational, and speech therapists and neuroscientists were least represented. Dr. Cernich said more work was needed to refine the specialties and manage duplication in the algorithm. She hoped that analyzing pairings across specialties could lead to some innovative partnership opportunities and identify missing specialties.

In closing, Dr. Cernich summarized some ongoing challenges. For example, some ICs represented in the plan did not participate in its development, so NICHD was assisting them with outreach, education, and coding validation. The RCDC was revised every year, so coding must be revalidated annually. In the current analysis, some projects that should have been included were missing, and some were included but did not belong. Changes to the NIH budget could affect all portfolios, and priorities within and across the NIH may change. Dr. Cernich stressed that the analysis presented was a snapshot and one proposed way of looking at data, but that a full analysis would be more complicated.

In the discussion that followed, Dr. Cernich was asked how she anticipated using the data from the portfolio analysis. She indicated the data would ensure that the NCMRR accurately portrayed the research it funds. However, 20% of NCMRR grants did not fall into an RCDC category and some RCDC rehabilitation projects funded by the NINDS did not actually involve rehabilitation. The results of analysis could affect future funding. Ralph Nitkin, added that, before the analysis, there was discussion with IC colleagues to develop some consensus about the operational definition of rehabilitation. The analysis provided baseline data and showed some weak spots, as well as some opportunities for collaboration. In response to a Board member question, Dr. Cernich said she would provide the data in terms of dollars spent. The data also illustrated that the Center for Scientific Review (CSR) assigned rehabilitation applications to several of the 100 standing study sections across the NIH, and success rates varied widely. Dr. Cernich said her office would be able to evaluate relative success rates of rehabilitation research proposals by study sections over time.

Dr. Cernich acknowledged the need for new categories, noting that the RCDC system was rooted in the Medical Subject Headings (MeSH) scheme, which may account for some of the questionable coding. For example, “physical rehabilitation” referred only to projects in which the subject was physically touched, so it excluded speech therapy. Dr. Cernich said more data were needed to better define categories and inform research planning.

Implementation and Update of the 21st Century Cures Act

Lisa Kaeser announced that fiscal year 2017 funding included $34 billion for NIH, much of which would fund initiatives under the Cures Act. The Cures Act resulted from years of hearings and negotiations in Congress, and it passed with overwhelming support. The Act demonstrated Congress’ strong interest in the development of medical treatments and cures. The legislation was unique in that it authorized spending, but unlike other such bills in which appropriators annually decide how much will actually be spent, the Cures Act mandated dollars for certain activities—such as the Cancer Moonshot, All of Us, and the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.

Among the new projects funded by the Cures Act was the Next Generation Researchers Initiative to support and retain new investigators. The law also provided more funding to increase the caps on the NIH loan repayment program. Other dollars were earmarked for Eureka Prize competitions, which incentivize high-risk, high-reward research. The law specified steps for the NIH to take to ensure that research was more inclusive of women, minorities, and children. The law loosened the travel restrictions for NIH staff attending professional conferences. To increase accountability, it established 5-year terms for IC directors (although terms are renewable). The law also created new data-sharing requirements and addressed data privacy.

She explained that NICHD will play a role in enacting several of the provisions, including a new pediatric research network that facilitates more international research and a task force on research relevant to pregnant and lactating women. As part of the Environmental Influences on Child Health Outcomes (ECHO) study, the program that evolved from the National Children’s Study, infrastructure would be developed in certain states with large rural, underserved areas, providing more access to pediatric clinical trials. NIH would host a workshop in June to gather more input from stakeholders on including children in research. Another task force would address research on medications used in pregnancy and postpartum, spearheaded by NICHD Deputy Director, Dr. Catherine Spong.

As part of the focus on medical rehabilitation research, the Research Plan on Rehabilitation was being updated. The Cures Act required the plan to be updated every 5 years with a focus on increasing coordination of efforts across the federal government. The law also directed the NIH to hold periodic scientific workshops to gather information that may inform the plan; reauthorized and updated membership on the NABMRR (e.g., adding the director of the Division of Program Coordination, Planning, and Strategic Initiatives); and gave the Secretary of Health and Human Services authority to enter into new interagency agreements. Ms. Kaeser noted that each aspect of the legislation required an implementation plan with timelines and objectives that would go to the NIH director for approval.

NCMRR Structure and Function

Ms. Kaeser explained that when the NCMRR was created in 1990, it was assigned to NICHD because the institute already had a focus on intellectual and developmental disabilities. Moreover, the NICHD had the broadest mission of any IC, which was thought to be useful in helping the NCMRR coordinate across ICs.

Since 1990, the NIH had been reauthorized three times. In 2012, Dr. Collins and former NICHD Director Dr. Alan Guttmacher established a blue-ribbon panel to look at medical rehabilitation research across the NIH. Although the panel recommended creating an independent institute or an office within the Office of the Director (OD), the Cures Act left the current structure intact. Dr. Cernich pointed out that within NICHD, the NCMRR was at the same level as an OD office; the NCMRR followed NICHD extramural policies but had a separate reporting structure, mission, and legislative authorization. The NCMRR also had an independent budget, so it could plan more prospectively than other branches. It also had full granting authority, meaning it was no longer limited to cofunding, and it could enter into interagency agreements (such as the agreement in development with the DoD). Dr. Cernich said the NCMRR was moving quickly to enact the recommendations of the blue-ribbon panel and the requirements of the Cures Act.

Dr. Cernich summed up that after 2 years directing the NCMRR, she felt it has more flexibility as a center than it would as an institute. By comparison, the Fogarty International Center had roughly the same budget as the NCMRR, but must pay for administrative, legal, and logistic support, while most of the NCMRR’s money went directly to research. As a center within NICHD, the NCMRR had strong support from a large institute, opportunities to coordinate with other institutes, and exceptional administrative support. Dr. Cernich indicated that she was not sure whether the NCMRR would be as effective if it were an independent institute. In addition, the NIH was mandated to support only a certain number of institutes, so promoting the NCMRR would mean demoting or eliminating another. Finally, if the NCMRR were located within another NIH institute, it would be limited to the diseases or conditions of interest to that institute and its related professions, whereas the NICHD had an incredibly broad mission. Dr. Nitkin added that if there were an independent NIH rehabilitation institute, other NIH institutes might relinquish some of their rehabilitation research priorities, leading to less research overall on the topic.

In response to Board discussion, Dr. Cernich explained that annual NCMRR budgets were based on historical averages, and allotted as a percentage of the current NICHD budget. Within that percentage, the NCMRR had flexibility on funding priorities. For example, the NCMRR supported a variety of research through SBIR.  Dr. Cernich indicated that it might be worth discussing the relatively large commitment of NCMRR funds to SBIR grants because they typically involved large out-year commitments if they entered the second phase. Dr. Cernich also pointed out that advocacy groups for rehabilitation research had siloed themselves from broader research priorities, but she hoped they would work more cooperatively to support the NICHD overall. As part of NICHD, the NCMRR could help other fields within NICHD, such as the Intellectual and Developmental Disabilities Branch and the Pediatric Trauma and Critical Illness Branch, to collaborate on broader patient outcomes. Collaboration among advocates was valuable because the NCMRR’s budget grew only if the broader NICHD’s budget grew.

Two Board members countered that being a center within the NICHD could be suppressing the NCMRR’s ability to get more money for research. One pointed out that if the NICHD was the right place for the NCMRR to be, the NCMRR should be a greater strategic priority for the institute. Dr. Cernich said that in other federal agencies, consolidating programs across agencies usually resulted in one large, less effective program. If the NIH consolidated all its rehabilitation research into one institute, it would rob resources from other institutes doing disease-oriented rehabilitation research. It was noted that the term “rehabilitation” was broad and interpreted in many ways, which complicated the debate.

A Board member observed that because the field was so broad, the NCMRR should be seeking to grow into an independent institute. Dr. Cernich again pointed to the resources available under the umbrella of NICHD as well as the breadth of experience and resources brought to bear by other institutes. If the NCMRR were an independent institute, it would have to cover an enormous range of research on its own. There was dissent on whether the current structure was effective in leveraging resources across the NIH or rather diluted the investment in and impact of the research. Dr. Cernich drew the analogy of diversification as an effective investment strategy.

An NIH staff member reiterated that rehabilitation was becoming part of the research agenda across many ICs. The notion of an independent institute kept coming up because of the perception that rehabilitation research did not have an independent voice. Elevating the visibility of the NCMRR could address that perception. Dr. Cernich indicated that Dr. Bianchi had been very supportive of the NCMRR’s ongoing efforts to become more widely known. A Board member suggested that the NCMRR take the lead in promoting the concept of exercise as rehabilitation more prominently, because it was the cheapest, most effective thing people could do to improve their health.

Concept Clearance

The NIH requires concept review and clearance of all proposed Requests for Applications (RFAs) and other key research activities. This review may be carried out in a number of different ways. For many institutes, concept review was a function of their national advisory councils or boards.

Dr. Joseph Bonner discussed a proposal to host a Pathway to Prevention workshop on the state of preventive medicine for wheelchair users. The workshop would address conditions resulting from chronic wheelchair use (such as shoulder injury or skin conditions) and access to general preventive care (such as cancer screening and vaccination). The Office of Disease Prevention hosted two Pathways to Prevention workshops per year, for which the Agency for Healthcare Research and Quality provided evidence reports that set the stage for the conferences. The process (report and conference) typically takes about 2-3 years. A brief outline of this concept was provided to the Board prior to the meeting.

In the discussion that followed, Board members enthusiastically supported the concept. It was hoped that the results would be widely disseminated. Because the meeting was not hosted by the NCMRR and was not specific to rehabilitation, other topics could also be addressed, such as the health risk of sitting or being inactive for long periods. There was an opportunity for those in the field to provide expertise on what constitutes mobility. One health consideration often overlooked was where people who use wheelchairs could go to exercise. Also, there was an assumption that wheelchair users would inevitably develop shoulder problems, but that is not proven; it is possible that exercise could prevent such problems.

Update and Closeout of Research Infrastructure Discussion

Dr. Ralph Nitkin described the Medical Rehabilitation Research Infrastructure Network, which was actually based on initial recommendations from the Board itself. The initial network (funded 2000 to 2005) sought to enhance research capacity and mentoring, with a specific requirement for geographical representation.

The next phase of the program (2005 to 2010), got additional support from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), allowing the network to grow to six sites with the primary focus of providing unique expertise relevant to rehabilitation research. Each site provided access to state-of-the-art research cores through workshops, offered online information and consultation, collaborations and mentorships, on site sabbaticals and visiting scholars, and even small pilot grants to allow researchers to be more competitive for larger research awards. The breadth of expertise available and collaborations across networks contributed to an increase in the number NIH rehabilitation research applications that went to a variety of ICs.

In phase III (2010 to 2015), applicants were encouraged to better cover the full range of issues in rehabilitation research. 23 applications were submitted and seven centers were funded, a slight increase in number with a 50% turnover in sites. The funded programs addressed a broad range of rehabilitation-relevant topics, including molecular genetics, impairments and plasticity, health services research, and technology assessment and product development. An interim analysis in 2014 highlighted some of the successful outcomes, outreach, collaborations, research productivity, and grants applications submitted to relevant NIH ICs. 

The FOA for the current phase of the network (2015 to 2020) encouraged further expansion into key domains such as clinical trial design, environmental engineering, individualized medical rehabilitation and dynamic reassessment, and applied behavioral supports for rehabilitation research, as well as other relevant domains proposed by applicants. Of the 20 applications received, about one-half attempted to address the highlighted areas (although none addressed applied behavioral supports). With continued support from the NIBIB and the NINDS, six sites were funded, three of which were new. Shortly after funding, the NCMRR put out an additional solicitation for a coordinating center.

In summing up the NCMRR commitment to research infrastructure, Dr. Nitkin indicated that in fiscal year 2016, the networks represented $4.7 million or 6.7% of the total NCMRR budget, and that 20% of these funds actually passed through to pilot grant funding. Dr. Nitkin asked the Board to consider whether this priority and level of commitment was appropriate. He presented some further outcome data, including outreach by each of the networks through website visits, collaborations, presentations, webinars, pilot grants, and support for visiting scholars. In response to earlier Board discussion, the current networks also provided several examples of leveraging opportunities with less-resourced institutions. They also created various research products, including databases, archived workshops, software, and newsletters. Grant applications resulting from the networks during this phase were just starting to come in to the NIH as well as the Veterans Administration (VA), the DoD, NSF, other agencies, and research foundations. The number of research publications citing the network support rose steadily through 2015. Dr. Nitkin suggested that these simple metrics began to demonstrate the impact of the infrastructure network.

Dr. Cernich indicated that the NCMRR was seeking the Board’s support to renew the network for a fifth phase and specific advice on how infrastructure support could be improved, such as what sort of metrics would be useful for evaluating their impact. A participant suggested surveying the field about awareness of the networks and increasing outreach to boost awareness. A Board member pointed out that the metrics did not address sustainability, which was key for a research network. Another recommended that the next iteration work to ensure that the infrastructure was coordinated with other research networks. A participant suggested Board members visit a site (in person or virtually). A Board member asked whether the host institutions had an incentive to invest in their network sites. Dr. Nitkin indicated that the host institution was required to provide infrastructure support as part of the peer review process, but another participant suggested that the NCMRR increase the responsibility of the host institutions to invest in these sites.

Asked whether the networks produced the desired outcomes as assessed by the coding exercise described earlier, Dr. Cernich explained that the research plan was developed after the network sites were funded. Also, she indicated that the coding exercise looked only at NICHD projects, but that a more comprehensive picture would be developed in the future. The research analysis could influence the funding criteria for the next iteration, but it would be unfair to judge the current network against goals that were not defined when it was funded.

Breakout Sessions

For the afternoon, Board members and visitors divided themselves into two working groups: one to discuss how best to achieve the strategic goal of supporting infrastructure for rehabilitation research, and the other to discuss the proposed data analysis (coding exercise) for evaluating implementation of the NIH Rehabilitation Research plan. As indicated below, each group summarized its discussion back to the entire group at the end of the day.
 
Breakout Group 1: Infrastructure
A Board member reporting for this breakout group indicated that there was continued support for a network of sites to maintain and promote infrastructure, but that there should be ways to measure the effectiveness of the approach. The measures should be standardized, but sites should also be able to select from a menu of measures, because they had different objectives. The 5-year funding cycles should be staggered so that the NCMRR could start up sites that target specific issues without having to wait 5 years.

More outreach and messaging was needed to raise awareness about the network. The NCMRR should look for resources within the NIH that can coordinate around outreach. Those affiliated with the network sites should be accountable for promoting the network at meetings and conferences. At the conclusion of a site’s funding, all the work products should be housed in a clearinghouse maintained by the NIH. In some cases, there may be opportunities to generate revenue from the use of the resources.

The NCMRR should post an open invitation for proposals and make sure the proposals align with the research plan. It should ensure that the network sites collaborate with physicians, have a role in mentorship and career support, and survey their communities about what is important. Institutions that house the sites should be required to provide support (in the form of facilities or otherwise). Larger sites should pair with institutions in underserved areas to meet the needs of the community.

Breakout Group 2: Data Analysis
Dr. Cernich helped provide the report back from the second group. They sought clarification about the level at which analysis was performed and better definitions of the first tier and the process of analysis. They also considered how to assess long-term impact. Dr. Cernich noted that projects would be recoded when they recompete for funding to reflect the progress over time. The NCMRR would consider whether the applied clinical research category should be broken down to include, for example, whether the project is a clinical trial and, if so, in what phase. In terms of translation potential, consideration would be given to categorizing applied research by themes. A proposal would be made to create a tier 2 infrastructure code for projects that were not clinical, translational, or basic research.

Further discussion addressed how to track investment to understand the value of research that did not appear to lead to changes in the field. Dr. Cernich said she would ask the trans-NIH committee to think about measuring return on investment (ROI) for knowledge that may not have an immediate impact. Questions remained about how much research affected the field if most of it was investigator-initiated and not directed by the NCMRR. If analysis indicated that the research plan did not have an impact, the NCMRR should consider how to stimulate the field. Dr. Cernich said the initial analysis sought to gather baseline data on funded research in the portfolio around rehabilitation. The current research plan did not outline goals for the field, but the analysis could inform goals described in the next version.

The group talked about including information on whether the grants analyzed were paired with specific, topic-oriented FOAs to learn whether impactful research comes from the community or from program direction. Dr. Cernich said the NCMRR can look at that issue over time. Much discussion centered on the level of granularity within the coding designations, so the NCMRR may consider how to take a more thematic look. Participants debated whether to report the number of projects or the dollar amounts or both, acknowledging that dollar amounts may yield a negative perception about ROI. Data on the impact of research could be gathered from progress reports or published data (and would be limited to research in humans), but the NCMRR may not have the capacity to take that on.

Participants sought more explanation about what drives changes to clinical guidelines (identified by iTrans). More data were needed to better understand the impact of research in the field. Participants also felt that better identifying who received funding (by specialty) was helpful, and the NCMRR was generating that data. The NCMRR could conduct a survey to validate the findings of the analysis. Finally, the group felt the next version of the research plan should include assessment.

A Board member said the analysis was great for funded grants but wondered whether it could be applied to unsuccessful grant applications to determine the factors of success and failure. Dr. Cernich said the universe of unsuccessful applications was very large. The NCMRR could explore what leads to success with help from the Office of Portfolio Analysis. Better understanding the failures could yield information about why some areas were underserved.

A Board member suggested that the NCMRR use the iTrans application to determine what proportion of research cited in a clinical guideline was funded by the NIH. Dr. Cernich agreed to look into the possibility. She also planned to convene a Board subcommittee to delve further into these questions.

Status of Board Member Nominations

Dr. Cernich said the federal hiring freeze and other restrictions were affecting the ability to appoint special government employees to serve on federal advisory boards. New candidates had been invited to join the Board, but their appointments were on hold. She asked those members who were rotating off the Board if they would consider remaining in their positions until the restrictions on special government employees were rescinded. An invitation to remain would be sent after the meeting to those individual members.

Update on Clinical Trials Policy

Dr. Meredith Temple-O’Connor summarized changes to the NIH policies on clinical trials. She emphasized that the NIH definition of a clinical trial was broad, and applicants should determine whether their proposed projects met the criteria so that they knew whether they were eligible for to apply under specific FOAs. Dr. Temple-O’Connor urged investigators to talk with program staff early on about potential studies and to continue communicating often. Changes that took effect January 1, 2017, included the following.

Options for required training now included a new course on behavioral/social science. Some FOAs would not accept applications involving clinical trials. FOAs will include a new form consolidating information about human subjects, inclusion, and trial information.
Implementation of the requirement that multisite research use a single institutional review board (IRB) was postponed to September 25, 2017. Advice on setting up a central IRB by using the NCATS Streamlined, Multisite, Accelerated Resources for Trials IRB Reliance Platform was available online. Protocol templates for phase II and III investigational new drug and device studies had been jointly developed by the U.S. Food and Drug Administration and the NIH to facilitate sharing data across systems; they should be available in May. Effective January 18, 2017, all NIH-funded clinical trials must be registered at ClinicalTrials.gov and must report results. If investigators at an institution failed to register and report all clinical trials, funding would be withheld for any new clinical trials at that institution.

Dr. Temple-O’Connor explained that the NICHD was working on FOAs that accept clinical trials and determining where ongoing trials fit in. Once the new policy was in place, parent announcements would no longer accept clinical trials. Dr. Temple-O’Connor anticipated an announcement this summer about the NICHD plan. The Office of Extramural Research (OER) was working on tools and interfaces through the NIH Commons and the Electronic Research Administration to extract information from applications and store it in a usable way. The NIH was also working on training NIH staff on good clinical practice, expanding outreach, and developing evaluation plans to assess the outcomes of policy changes.

In the discussion that followed, Dr. Temple-O’Connor acknowledged concerns that ClinicalTrials.gov was not optimally designed to accommodate behavioral and social science; she suggested Board members bring specific concerns to Dr. Cernich for discussion with OER. A Board member asked for better published guidance for investigators on uploading information to ClinicalTrials.gov. Dr. Temple-O’Connor asked for specific examples that could be passed on to the site developers.

Dr. Nitkin said more communication and training about these policies were needed, especially for junior investigators. Dr. Temple-O’Connor said the NICHD was developing slide presentations that staff could use for training, including an interactive slide set. A decision tree was designed to help users quickly identify what kinds of research constitute a clinical trial. In addition, the NIH was beefing up peer review to ensure that all panels had the right expertise to assess applications using the trial-specific criteria of the FOAs. Other suggestions for reaching junior investigators were welcomed.

In response to a Board member, Dr. Temple-O’Connor said the NIH envisioned that each IC would have its own suite of FOAs, but that arrangement was now presenting complications. Using a consolidated form for information should increase flexibility in implementing FOAs while retaining the goal of trial-specific FOAs. However, there was some concern that applicants will “shop around” for an IC that has an FOA they like.

A Board member called for better communication and advice for researchers adapting existing trials to fit the new policies. For example, it was challenging to incorporate information on ClinicalTrials.gov for studies that were not originally defined as clinical trials. Dr. Temple-O’Connor acknowledged that the process could be challenging, but said that efforts were underway to improve it. She again asked for examples of specific concerns to be addressed. OER was working on an implementation plan for submitting information to ClinicalTrials.gov. Dr. Cernich added that one of the sites in the Research Infrastructure Network was developing guidance on conducting clinical trials in rehabilitation. She urged participants to raise concerns and offer specific suggestions that the NCMRR could address.

Update on Cerebral Palsy (CP) Research Plan

Dr. Jim Koenig began by indicating that a Senate appropriations subcommittee urged the NIH to develop a 5-year strategic plan for CP research. Jointly, NICHD and NINDS held two workshops to assess the state of the science and research gaps as a basis for the plan. They partnered with key stakeholders, including patient advocacy groups, to ensure that a thorough, cohesive plan was created.

Dr. Koenig presented highlights of the draft plan, describing the three priority areas—basic and translational research, clinical research, and workforce development—and giving examples of the types of research to be conducted for each. He noted, for example, that the field had not done a good job addressing rehabilitation, treatment options, and therapeutic strategies for adults, so clinical research should better address the entire lifespan. The clinical research priorities also responded to community feedback about underreporting of treatment options. The workforce development priority leveraged NIH’s capacity to attract new people to the field. One proposal suggested creating a departmental training (T32) grant to increase workforce training.

Among the accomplishments so far, the NIH established the CP Research Network to maximize the potential of databases and registries. NINDS and the American Academy for Cerebral Palsy and Developmental Medicine published common data elements to facilitate data sharing; the result was available online and open for feedback. CP NOW developed a CP toolkit for families with a new diagnosis of CP.

The draft strategic plan was posted online for feedback. Comments were generally positive. Most comments centered on the need to enhance emphasis on early diagnosis, evaluate placental involvement, address treatment, and incorporate patient-centered research and outcomes. Commenters also called for more research on genetics and genomics, which Dr. Koenig said NICHD and NINDS would incorporate into the plan. Next steps included finalizing the plan and sharing it with the community, developing research initiatives to fill the gaps identified, and gaining final approval for the plan and proposed initiatives. Dr. Koenig hoped the plan would be embraced by the whole community and help move the field forward.

A Board member asked what efforts were feasible given the current fiscal climate and the poor track record of getting treatments to those who needed them. Dr. Koenig responded that the next step would be addressing feasibility, but the future financial landscape was unpredictable. Dr. Nitkin hoped the plan would spark interest among the research community. Dr. Koenig noted that CP had been under the radar, so having a plan would attract attention and acknowledge the importance of research in this area. He added that it was critical that the CP community advocate for bringing more people in to the field. He also hoped for more funding for CP research at NIH. A participant said the plan shines a light on the important, high-value areas for research. Also, a consortium formed to promote genetics research on CP; such a mechanism could have a high impact and therefore attract funding.

A Board member asked whether consideration was given to studying comorbidities commonly seen with CP (such as epilepsy and autism). Dr. Koenig said the issue was being looked at now. He stressed that more investment was needed to understand common themes of developmental disorders that may be applicable across conditions.

Update on StrokeNet

Dr. Scott Janis outlined the public health burden of stroke. Overall, the NIH invested $288 million in stroke research in fiscal year 2015, mostly through NINDS. During strategic planning a few years ago, several groups at NINDS identified the need for infrastructure to support clinical projects in the research portfolio. As a result, StrokeNet was established in 2013. It encompassed 25 regional centers, distributed around the country near the large centers for stroke treatment. Dr. Janis said efforts were underway to locate some regional centers in the middle of the country. The infrastructure cost $11 million per year. The network represented a good balance of recovery and treatment research.

Ideally, StrokeNet would increase efficiency of research trials and help balance the portfolio with an eye toward the future. It should develop a research database and enable more collaboration, locally and even internationally. Many specialties played a part in patient care around stroke; StrokeNet brought representatives from rehabilitation, prevention, and acute treatment to the table. Ultimately, Dr. Janis said, the goals were to reduce the global impact of stroke and also to spur the field to do things differently.

StrokeNet included 350 stroke hospitals and provided a central IRB and central payment system to facilitate cooperation. It brought together scientific working groups to tackle relevant issues and relied on resource cores to address ongoing needs. The network covered about half of the U.S. population, although reaching rural areas remained a challenge.

Dr. Janis described some of the leadership teams working across StrokeNet, such as the group based at the University of Cincinnati that incorporated a strong educational component in its efforts to fill the workforce pipeline. The scientific working groups pulled people from all the network centers to design and fine-tune projects. Dr. Janis said the NIH was beginning to see collaborations across the network that were addressing research gaps. StrokeNet advisory groups dealt with issues such as competing trials, recruitment concerns, and inclusion of special populations.

One of the regional centers created an integrated, easy-to-use database that was adopted by all the centers to facilitate study start-up. The database used an open network that allowed others to work with the data. The approach was very efficient and also provided a good training opportunity. Each center had dedicated funding for training and annual fellowships. The network sought to increase the demographic diversity of trainees and engages representatives of more new disciplines every year. The network aimed to retain trainees in the field, and early data suggested that more trainees were staying in academic research after their fellowships.

Dr. Janis summarized the process of trial development, refinement, and start-up, pointing out that the research was investigator-initiated. Proposals went through a review process, and NINDS could now link investigators with complementary projects so that they could collaborate and strengthen their efforts. Two large trials had been initiated: Diffusion and Perfusion Weighted Imaging Evaluation for Understanding Stroke Evolution (DEFUSE 3) and Atrial Cardiopathy and Antithrombotic Drugs in Prevention after Cryptogenic Stroke (ARCADIA). StrokeNet had been instrumental in identifying eligible trial subjects and centers that could participate. Dr. Janis added that the use of a central IRB had been eye-opening but effective.

StrokeNet interacted with other networks. For example, the VA hospitals agreed to use a central IRB model that dovetailed with StrokeNet. The American Heart Association’s Get with the Guidelines® database was linked to StrokeNet, which allowed for feasibility studies. StrokeNet leaders met regularly with leaders of the Global Stroke Alliance.

Several other large studies were underway when StrokeNet began and had since become part of the network, such as the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) and the MISTIE Intracerebral Hemorrhage Trial. Dr. Janis described the Telerehab Trial, funded by the NCMRR and supported by StrokeNet. Initiating the study had been challenging, but enrollment was progressing very well, and valuable lessons were been learned about, for example, speeding up the start-up process for individual sites.

Dr. Janis said the NINDS hoped to raise awareness about StrokeNet and bring broader representation into the network. One of the working groups published a white paper on stroke recovery and rehabilitation. Three additional rehabilitation trials were been submitted for StrokeNet consideration. NINDS and the NCMRR were planning a workshop to discuss opportunities and priorities in recovery trials. Dr. Janis concluded that StrokeNet was designed to foster a new culture that would move the science forward.

Dr. Cernich said that she served on the oversight board for StrokeNet, which hoped to encourage more recovery trials and address limiting factors. Dr. Nitkin noted that research would help identify and optimize the “active ingredients” within a comprehensive rehabilitation approach that contributed to effective recovery.

A Board member pointed out that uptake of effective interventions may be limited for several reasons. First, studies that were not designed to address costs could not demonstrate cost-effectiveness. In addition, researchers must clear a higher bar for proving success than, for example, those studying drugs, because new interventions must show a significant enough increased benefit when compared with traditional care that may be fairly effective (rather than comparison with a placebo). On top of that, there was no consensus about what constituted traditional care. Dr. Janis said workshops and other avenues sought to address these kinds of concerns, but more and better communication was needed.

A Board member wondered how the StrokeNet infrastructure could be used to support work in other fields. Dr. Janis said the NIH Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) encompassed neurology research other than stroke and had about 10 studies underway. Also, NINDS was partnering with the National Heart, Lung, and Blood Institute (NHLBI) and the NCATS in the Strategies to Innovate Emergency Care Clinical Trials Network (SIREN).

Dr. Cernich proposed that the Board discuss at a future meeting the possibility of transforming the Research Infrastructure Network into a clinical trials network. She said a key lesson from StrokeNet was that trying to conduct clinical trials, especially research involving devices, with a small amount of funds was not entirely worthwhile. A Board member felt that the level of evidence required by the NIH just to propose a study stifled innovative research; he asked whether the NIH would support exploratory research. Dr. Janis said the NIH did fund such research, but the success of any given application depended on the reviewers. NINDS was trying to bring researchers together around novel approaches. Dr. Cernich added that NIH’s pioneer awards specifically targeted unconventional research.

Scientific Presentation: Promoting Motor Recovery in Stroke: From Vermicelli to Neuroprosthetics

Dr. Randy Nudo summarized theories around stroke recovery and current research. Scientists long believed that stroke recovery was related either to the proportion of impairment or the degree of spinal involvement. Neuroscientists aimed to understand why brains recover, because, Dr. Nudo maintained, a brain affected by focal stroke was not just a normal brain with a portion “missing” but rather a completely reorganized system.

Functional magnetic resonance imaging allowed visualization of complex systems at work. One theory posited that areas connected to the site of injury became dysfunctional even if they were not directly injured (known as diaschisis) and recovery must relate to some reversal of this state. Others suggested that improvement was not entirely due to recovery but rather largely the result of compensation. “Superstars” of recovery demonstrated tremendous compensation (a good example of neuroplasticity). Current research sought to reveal how changes in the brain led to improved function.

Early research using brain mapping in animals determined that the maps (or patterns of brain use) were driven by use. Imaging showed that much of the reduction in function in certain parts of the brain was caused by disuse, but some of that function was reversible. Both disuse and skilled use drove changes in the maps. With rehabilitation training using tasks, animals got better and faster at the tasks, and the maps showed expansion not seen in animals with no rehabilitation.

Even when injury or lesions occured in the brain, some premotor cortex representation remained. In primate studies, that representation could expand to the size of the lesion. With rehabilitation, it grew even more, and new fibers formed. Dr. Nudo believed the growth demonstrated the brain’s mechanism for re-establishing somatosensory pathways. A conundrum of using mapping, however, was that the maps did not change at the same pace as the physical functions. In animals, it took a while for the brain maps to catch up to performance; thus, there may be changes in behavior that researchers missed by using standard clinical scales of measurement. Dr. Nudo believed the maturation of brain maps resulted from the maturation of new fibers, formation of synapses, and changes in kinematics.

Dr. Nudo and others were applying neurophysiology tools to get at what individual neurons do. Specifically, if an area of the brain altered function to support new behavior, was it because neurons altered to become more like the missing portions, or did a preparatory neuron turn into an execution neuron, integrating somatosensory and motor inputs into discrete movement?

The field of neuromodulation was growing, and researchers had evaluated lots of new approaches, such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and epidural therapy. All of the research tended to employ preprogrammed, open-loop stimulation. Some were starting to use closed-loop modulation. Dr. Nudo and colleagues were evaluating embedded devices that recorded signal processing and provide microstimulation (in this case, to prohibit epileptic seizures). Another study was taking a similar approach with deep brain stimulation. To be effective, a neurostimulation device must detect a spike in activity and respond with stimulation within 50 milliseconds.

With funding from the DoD, Dr. Nudo and colleagues developed and patented a tiny neurostimulation device and tested it in rats, with promising results. However, they must overcome enormous challenges before it can be tested in humans. First, there was no precedent for testing a computerized device implanted in the brain, so an investigational device exemption (IDE) would be required. That step alone could cost as much as $20 million, putting the research beyond the capacity of NIH and academic funders. Efforts were underway to commercialize the endeavor and seek venture capital funding, but investment was hampered by the anticipated time to ROI, estimated at 10 to 15 years. Dr. Nudo observed that researchers had no clear mechanisms to fund complex, invasive technology like this. However, high-profile technology developers recently expressed interest in brain devices, drawing a lot of attention to the field, which could spur investment.

Dr. Nudo concluded that neuroplasticity was the logical mechanistic basis for recovery of function following stroke. The biomarkers of neuroplasticity could be examined in various ways, at various levels of complexity. The technology was increasingly sophisticated and offered a lot of potential.

Comments from Retiring Board Members

Dr. Sureyya Dikmen thanked the Board for the opportunity to serve. She said that when she was an intern, she was nervous about her rehabilitation medicine rotation, but once she started, she was deeply impressed by the many different avenues to improve function. She has since studied recovery of function following traumatic brain injury in various settings with various approaches, but none have worked. She hoped the future would allow for better clinical trials. Dr. Dikmen reminded the group that rehabilitation involved many degrees of freedom and quality of life, and she appreciated all that the Board and the NCMRR are doing.

Dr. Dennis Matthews echoed his appreciation, noting that he especially enjoyed getting to know the other Board members and learning about their tremendous talents in the field. He said he witnessed the blue-ribbon panel and the growth and development of the NCMRR. He thanked Dr. Nitkin and expressed his belief that the organization is in good hands with Dr. Cernich at the helm. Efforts to network with other ICs had already been exceptional. Dr. Matthews asked the Board to remember the pediatric population, which has been ignored for way too long at all the other ICs and is a very important component of rehabilitation.

Dr. Richard Shields thanked the NIH for the opportunity to serve. He said that more than 10 years ago, at a meeting with then-NIH Director Dr. Elias Zerhouni, when the question of rehabilitation having its own institute was raised, it was clear that the level of appreciation that exists today was not there. Just 3 years ago, at a meeting in Dr. Francis Collins’ office, the same question arose, and Dr. Collins demonstrated an incredible understanding of what rehabilitation research was, is, and will be. Moreover, Dr. Collins had already thought about how to best position rehabilitation research within the NIH. Under the leadership of Dr. Nitkin and colleagues, the NCMRR not only secured its own budget but also received a bump in funding. Dr. Shields said that accomplishment often gets overlooked as new people rotate on to the board. He concluded that his term on the Board had been “a great ride.”

Solicitation of New Topics for the December 2017 Meeting

The following possible topics were proposed:

  • Presentation on combination therapies (such as pharmaceutical treatment, brain stimulation, behavioral therapy, and exercise)
  • Updates on clinical trials
  • Presentation on implementation science around rehabilitation research in an effort to better understand how the NIH findings make their way into clinical practice
  • A more in-depth review of work at one of the Research Infrastructure Network sites, such as an overview of a big data interface
  • Assessment of work going on at other ICs that could be coalesced by the NCMRR into scalable practices

Dr. Cernich noted that the NCMRR was hosting a workshop on medical devices and rehabilitation that aimed to reveal how to use federal funding for research to support an IDE application and how to navigate the world of private investment. A participant requested a briefing about the conference at the next meeting addressing the “valley of death”—that is, the gap between research and commercialization. Dr. Cernich said she could provide a summary of findings of the conference.

Closing and Adjournment

Dr. Nitkin thanked the participants for their time and expertise. He adjourned the meeting at 11:53 a.m.


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